Enzymes in STP

ENZYMES IN SIGNAL TRANSDUCTION PATHWAYS

Table of contents :


(non-receptor) protein serine / threonine kinases (non-receptor) protein tyrosine kinases (PTK) protein threonine / tyrosine kinases protein histidine kinases lipid kinases lipid phosphatases protein serine / threonine phosphatase protein tyrosine phosphatase (PTP) dual specificity protein serine / tyrosine phosphatase protein threonine / tyrosine phosphatase caspases (non-receptor) guanlyate cyclases (GC) adenylate cyclases (AC) phosphodiesterases (PDE) nucleotide metabolism DNA topoisomerases	histone deacetylase (HD / HDAC) histone acetyltransferase (HAT) ATPases phospholipases ANRP AAP Ras-like superfamily GNRP / GEF / GDS GAP GEF & GAP GDI eicosanoid metabolism neurotransmitter anabolism neurotransmitter catabolism Bcl-2 family cytochromes ATP-binding cassette (ABC) proteins matrix metalloproteinases (MMPs)


Enzyme family	enzyme name	substrate(s)	activator(s)	inhibitor(s)
	UDP-glucose ceramide glucosyltransferase (UGCG) / ceramide glucosyltransferase / glucosylceramide synthase (GCS)	UDP-glucose + ceramide => glucosylceramide		N-butyl-deoxynojirimycin (NB-DNJ) / miglustat / OGT 918 (Vevesca^®, Zavesca^® in Europe) OGT2378 GENZ-112638^ref
	ceramide kinase (CERK)^ref
	mammalian target of rapamycin (mTOR)			6-dimethylaminopurine sirolimus / rapamycin (Rapamune^®; in drug-eluting stents sold under the trade name Cypher^®) complexed to FKBP1A / FKBP12 everolimus / SDZ RAD / 40-O-(2-hydroxyethyl)-rapamycin (Certican^®) temsirolimus / CCI-779 (Torisel^®) deforolimus / AP23573 zotarolimus (in drug-eluting stents sold under the trade name Endeavor^® and ZoMaxx^®) biolimus (in drug-eluting stents sold under the trade name Axxess^®) umirolimus ridaforolimus / AP23573 ABI-009 TOP-216 BEZ-235 NVP-BEZ235 ATP-competitive mTOR inhibitors : AZD8055
	IMP dehydrogenase (IMPDH) 2, a de novo guanine (Gua) ribo- and 2'-deoxyribonucleotides synthesis enzyme expressed in T- and B-lymphocytes and up-regulated upon cell activation			less potent on IMPDH 1, expressed in most cell types. mycophenolate mofetil (MFF) / RS-61443 (Cell-cept^®; Myfortic^® is the enteric-coated formulation designed to protect the upper G-I tract) is the 2-morpholinoethyl ester prodrug of mycophenolic acid (MPA) Catabolyzed to the inactive mycophenolic acid glucuronide (MPAG). mizoribine (MZB) VX-497 ribavirin AVN944
	dihydroorotate dehydrogenase (DHODH), an enzyme in the de novo pathway of pyrimidine synthesis			leflunomide (Arava^®) => A77 1726 is noncompetitive versus ubiquinone polyporic acid brequinar / DUP-785 is a competitive inhibitor versus ubiquinone 2-phenyl 5-quinolinecarboxylic acid (PQC), the core moiety of brequinar, also shows competitive inhibition versus ubiquinone HR325 KF20444 barbituric acid (a competitive inhibitor versus DHO)
	purine nucleoside phosphorylase (PNP)			forodesine / immuncillin H / BCX-1777 / immucillin hypoxanthine / [1(S)-1-(9-deazahypoxanthin-9-yl)-1,4-dideoxy-1,4-imino-D-ribitol]
	betaine-homocysteine-S-methyltransferase (BHMT)			S-(d-carboxybutyl)-DL-homocysteine (CBHcy)^ref
secretase	alpha-secretase is a zinc metalloproteinase, and several members of the adamalysin family of proteins, tumour necrosis factor-alpha convertase (TACE, ADAM17), ADAM10, and ADAM9, all fulfil some of the criteria required of alpha-secretase^ref
	beta-secretase : b-site APP-cleaving enzyme 1 (BACE1) and BACE2
	gamma-secretase complex Nicastrin (Nct) / APH2, APH-1A/APH-1B, and PSENEN / PEN-2, when combined with a heterodimer of endoproteolysed presenilin (presenilin 1 (PS1) and PS2) fragments, form a stable, catalytically active, high-molecular-mass protein complex. This unusual aspartyl protease is the founding member of a novel class of proteases that carry out intramembrane cleavage, resulting in peptide-bond hydrolysis within the hydrophobic environs of the lipid bilayer			gamma-secretase inhibitors (GSI) : LY450139


	polo-like kinase (PLK) 1			volasertib / BI 6727
	PLK2
	PLK3
	PLK4			CFI-400945
protein serine / threonine kinases	Raf1			BAY 43-9006 / sorafenib (Nexavar^®) (also inhibits RTKs FLT-3 , VEGFR2 and c-KIT )
	BRAF			vemurafenib / PLX4032 (Zelboraf^®) dabrafenib / GSK2118436 (Tafinlar^®)
	GSK-3b			6-dimethylaminopurine 6-bromoindirubin-3'-oxime (BIO) Li⁺
	CDK1 & CDK2			6-dimethylaminopurine flavopiridol / alvocidib UCN-01 / 7-hydroxystaurosporine seliciclib (CYC202; R-roscovitine) indirubin
	CDK9			6-dimethylaminopurine flavopiridol / alvocidib
	p70^S6K			6-dimethylaminopurine
	MAPKKKs			6-dimethylaminopurine
	p38 / MAPK1 / ERK2			6-dimethylaminopurine ; SB202190 ; SB203580 ; SB281832 ; PD169316 ; RWJ-67657 ; BiRB0797 ; Ro320-1195 VX-745 SCIO-469
	p44 / MAPK3 / ERK1			6-dimethylaminopurine U0126
	RhoA kinase (ROCK1)			6-dimethylaminopurine Y-27632 [(R)-(+)-trans-N-(4-pyridyl)-4- (1-aminoethyl)cyclohexanecarboxamide]
	PKA : C₂R₂ catalytic subunit (C) : except that for mCb₃, it is miristoylated but it doesn't anchor it on the cytoplasmic side; they can phosphorylate RII subunits. Ca₁ (it can undergo autophosphorylation) Ca₂ (inactive) Ca-s bCb₁ (it can undergo autophosphorylation) bCb₂ mCb₁ mCb₂ mCb₃ Cg (it doesn't bind PKI; it can undergo autophosphorylation) PrkX1 regulatory subunit RIa RIb RIIa RIIb		Sp-8-Br-cAMPS ; dibutiryl-cAMP (dbcAMP) H8 (N-(2- methylaminoethyl) -5-isochinoline sulfonamide. A compound derived from calmodulin antagonists that does no longer possess calmodulin -inhibitory activity.) H89	6-dimethylaminopurine
	PKB PKBa / Akt1 / RAC-PKa PKBb / Akt2 / RAC-PKb PKBg / Akt3 / RAC-PKg			6-dimethylaminopurine IL-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate perifosine [octadecyl-(1,1-dimethyl-piperidinio-4-yl)-phosphate]
	PKC (PS-dependent) DAG- and Ca²⁺-dependent or conventional (cPKC) PKCa PKCb isozymes PKCbI PKCbII PKCg DAG-dependent and Ca²⁺-independent or novel (nPKC) PKCd PKCe PKCh PKCq DAG- and Ca²⁺-independent, PI-3,4,5-P₃-dependent or atypical (aPKC) PKCz PKCl / i PKCm / PKD PRK / PKN 1, 2 and 3		phorbol esters bryostatins	6-dimethylaminopurine calphostin C staurosporine UCN-01 / 7-hydroxystaurosporine ruboxistaurin mesylate (PKCb-specific) Go6976 K-252a H7 GF 109203X rottlerin enzastaurin (LY317615.HCl) sotrastaurin (AEB-071) (source : Novartis) PKC412
	DNA-PK			6-dimethylaminopurine
	CaMK			6-dimethylaminopurine
(non-receptor ) protein tyrosine kinases (PTK)	Janus family (so named as they also have an inactive Ser/Thr kinase domain) p130^JAK1 p130^JAK2 JAK3 TYK1 / LTK p135^TYK2			JAK2 selective (not selective for JAK2-V617F) : INCB018424 / ruxolitinib (Jakafi^©) (source : Incyte/Novartis)^ref XL019 (source : Exelixis) TG101348 / SAR302503 (source : TargeGen) NS-018 BMS911543 SU5146 AZD1418 (JAK1/2) CEP701 (JAK2/3) CYT387 (JAK1/2, Tyk2) tasocitinib / CP690550 / tofacitinib SB1518 / pacritinib (JAK2, Tyk2) LY2784544 is a small molecule selective mutant JAK2 inhibitor
	Src family (in some RCTKs the SH4 domain is also palmitoylated) p60^c-Src yrk / Alk2 (in Mus musculus) p62^Yes1 c-Abl1 p59.4^{Fgr / Src2} p59^Fyn p56^Lck p53-56^Lyn p57^Hck p55^Blk			PP2, middle t antigen from SV40 / / CGP57148 imatinib mesylate / STI 571 (Gleevec / Glivec^©) dasatinib / BMS-354825 (Sprycel^©) nilotinib (Tasigna^©) bosutinib / SKI-606 (Bosulif^©) ponatinib (Iclusig^©) bafetinib / INNO-406 / / / / / / A-770041 (Lck-selective)
	Bruton's kinase (Btk)			ONO-WG-307 LFM-A13 dasatinib (Sprycel^©) CC-292 ibrutinib / PCI-32765 (Imbruvica^©)
	Interleukin-2 Inducible Kinase (ITK)
protein threonine / tyrosine kinases	MAPKK / MEK MAPKK1 / MEK1			UO126 trametinib (Mekinist^©) PD98059 LF from Bacillus anthracis
	wee1
	mik1
protein histidine kinases (only in plants and Bacteria)	ETR1, ETR2, EIN4, ERS1, ERS2 (coupled to ethylene receptor)
	CRE1 / AHK4 (coupled to cytokinin receptor)
	CKI1, CKI2 (coupled to cytokinin receptor)
	ATHK1 (osmosensor)
lipid kinases	PI3K class I (+ RasBD) subclass IA (stimulated also by FRP ) p110a => PI3Ka p110b => PI3Kb p110d => PI3Kd adapters or regulatory subunits : p85a p85b p55a p55g => PI3Kg p50a subclass IB (stimulated by Gbg subunits) p110g adapter or regulatory subunit : p101 class II (+ C2 domain) PI3KC2a adapter or regulatory subunit : clathrin (Lca + Lcb + Hc) PI3KC2b PI3KC2g class III : VPS34 adapter or regulatory subunit : p150		middle t antigen from SV40	LY294002 radicicol wortmannin idelalisib / GS-1101 / CAL-101 NVP-BKM120
	diacylglycerol kinase (DAGK) DAGK1 / a DAGK2 / b DAGK d DAGK3 / g DAGK4 / 7 / q DAGK5 / z DAGK6 / e DAGK h DAGK i			R59022
	sphingosine kinase 1 (SphK1) sphingosine kinase 2			N,N-dimethylsphingosine (DMS) dihydro-sphingosine (DHS)
lipid phosphatases	IP phosphatase			Li⁺
protein serine / threonine phosphatase	PP1 / PPI catalytic a b g activated by PKB regulatory (inhibitory) 1A / I1 1B 1C 2 3A 3B / 4 3C / 5 3D / 6 3E 3F 3G 7 8 9A 9B 10 11 12A 12B 12C 13A / TP53BP2 13B 14A 14B 14C 14D 15A 15B 16A 16B	glycogen phosphorylase (inhibited) p105^Rb (inhibited) p80^cdc25 (inhibited) eIF2a (activated) glycogen synthase (activated) IkBa (activated) X (activated or inhibited)		tautomycin tautomycetin (TMC) iodoacetic acid sodium orthovanadate sodium pervanadate (VO₄^3-) okadaic acid (weak inhibition) microcystin-LR
	PP2A / PPIIA			tautomycin iodoacetic acid sodium orthovanadate sodium pervanadate (VO₄^3-) okadaic acid (strong inhibition) small t antigen from SV40 calyculin A microcystin-LR
	PP2B / PPIIB / PP3 / PPIII / calcineurin (subunit A / catalytic : a, b or g; subunit B / regulatory : I or II; Ca²⁺CaM-dependent)	T lymphocytes		iodoacetic acid sodium orthovanadate sodium pervanadate (VO₄^3-) cyclosporine A complexed to cyclophilin 40 or neurophilin tacrolimus (acronym for Tsukuba macrolide immunosuppressive) (FK506^®) (from Streptomyces tsukubaensis) complexed to FKBP1A / FKBP12 or FKBP4 / FKBP52
	PP2C / PPIIC
	PP4 / PPIV			iodoacetic acid sodium orthovanadate sodium pervanadate (VO₄^3-)
	PP5 / PPV			iodoacetic acid sodium orthovanadate sodium pervanadate (VO₄^3-)
	PP6 / PPVI			iodoacetic acid sodium orthovanadate sodium pervanadate (VO₄^3-)
	PP7 / PPVII			iodoacetic acid sodium orthovanadate sodium pervanadate (VO₄^3-)
protein tyrosine phosphatase (PTP)	SHP-1 / PTP-1C / hematopoetic cell phosphatase (HCP) / SHPTP1 / SHP / PTPN6			sodium stilbogluconate (SSG) iodoacetic acid sodium orthovanadate sodium pervanadate (VO₄^3-)
	SHP-2 / PTP-2C / Syp / PTP-1D / SH-PTP2 / PTPN11			iodoacetic acid sodium orthovanadate sodium pervanadate (VO₄^3-)
	hPTP1E / PTPBAS / FAP1 PTP2E (Rattus norvegicus) R-PTP y			iodoacetic acid sodium orthovanadate sodium pervanadate (VO₄^3-)
dual specificity protein serine / tyrosine phosphatase	DUSP1 / MKP1 / PTPN10 DUSP2 / PAC1 DUSP3 / VHR DUSP4 / MKP2 DUSP5 DUSP6 / MKP3 DUSP7 DUSP8 DUSP9 DUSP10 DUSP11 DUSP12 DUSP13 DUSP14 DUSP15 DUSP16 DUSP17 / DUSP19			VO₄^3-
protein threonine / tyrosine phosphatase	Cdc25 Cdc25A Cdc25B Cdc25C			VO₄^3-
caspases	caspase 1 / interleukin-1 converting enzyme (ICE) : 2 20-kDa and 2 10-kDa subunits (monocytes, neutrophils , resting and activated T lymphocytes, placenta tissue and several B-lymphoblastoid cell lines)	pro-IL-1b and pro-IL-18		Cbz-Val-Ala-Asp(OMe) -fluoromethylketone (zVAD) crmA from cowpox virus P35 from Baculovirus spp. pralnacasan
	caspase 2			Cbz-Val-Ala-Asp(OMe) -fluoromethylketone (zVAD)
	caspase 3	poly (ADP-ribose) polymerase (PARP)		Cbz-Val-Ala-Asp(OMe) -fluoromethylketone (zVAD)
	caspase 4			Cbz-Val-Ala-Asp(OMe) -fluoromethylketone (zVAD)
	caspase 5			Cbz-Val-Ala-Asp(OMe) -fluoromethylketone (zVAD)
	caspase 6			Cbz-Val-Ala-Asp(OMe) -fluoromethylketone (zVAD)
	caspase 7			Cbz-Val-Ala-Asp(OMe) -fluoromethylketone (zVAD)
	caspase 8			Cbz-Val-Ala-Asp(OMe) -fluoromethylketone (zVAD) Cbz-Leu-Glu-Thr-Asp(OMe) -fluoromethylketone (zLETD)
	caspase 9			Cbz-Val-Ala-Asp(OMe) -fluoromethylketone (zVAD) Cbz-Leu-Glu-His-Asp(OMe) -fluoromethylketone (zLEHD
	caspase 10			Cbz-Val-Ala-Asp(OMe) -fluoromethylketone (zVAD)
	caspase 11			Cbz-Val-Ala-Asp(OMe) -fluoromethylketone (zVAD)
	caspase 12			Cbz-Val-Ala-Asp(OMe) -fluoromethylketone (zVAD)
	caspase 13			Cbz-Val-Ala-Asp(OMe) -fluoromethylketone (zVAD)
	caspase 14			Cbz-Val-Ala-Asp(OMe) -fluoromethylketone (zVAD)
(non-receptor ) guanlyate cyclases (GC)	guanlyate cyclase 1A2		YC-1 isoliquiritigenin	1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ) N-methylhydroxylamine
adenylate cyclases (AC)	AC1 (+ Ga_s, PKC, Ca²⁺CaM ;- Ga_i, Ga₀, Ga_z, b₅g₂, b₁g₂, Ca²⁺) AC2 (+ : PKC; - : b₅g₂, b₁g₂) AC3 (+ : PKC, Ca²⁺CaM ; - : Ga_i, Ca²⁺) AC4 (+ : ; - : PKC) AC5 (+ : PKC; - : PKA, Ga₀, Ga_i, Ga_z, Ca²⁺), AC6 (+ : ; - : PKA, Ga₀, Ga_i, Ca²⁺) AC7 (+ : PKC, Ca²⁺CaM ; - : ) AC8(+ : ; - : ) AC9 (+ : ; - : Ca²⁺)	ATP => cAMP + PP_i	forskolin forskolin forskolin forskolin forskolin forskolin forskolin forskolin /
phosphodiesterases (PDE) (they all are also inhibited by xanthines (e.g. aminophylline pentoxyphylline (Trental^©) propentophylline (Karsivan^©) ... are inhibitors of TNF-a release in monocytes activated by AGEs) and methylxanthines (e.g. caffeine / teine teophylline teobromine diphylline enprofylline papaverine ) ..., but at concentrations >> those acting on P1 purinoceptors)	PDE1A PDE1B PDE1C PDE2A PDE3A PDE3B PDE7A PDE8A PDE9A	cGMP > cAMP cGMP > cAMP cGMP and cAMP cGMP and cAMP cGMP and cAMP cGMP and cAMP cAMP cNMP cAMP ? cAMP cAMP cGMP		vinpocetine (Cavinton^®, Remedial^®, and Vincaton^®) EHNA milrinone (Primacor^®) inamrinone (Inocor^®, Inamrinone Injection^®) / amrinone (Amrinone lactate^®), SelCIDs enoximone (Perfane^®) lixazinone / RS-82856 imadozan cilostamide rolipram zaprinast 3-isobutyl-1-methylxanthine (IBMX) D-22888 (type IV) zardaverine (type III and IV) vesnarinone / OPS 8212 (Arkin-Z^®, Otsuka^®) pimobendan levosimendan (Simdax^®) BMY 20844 RA233 KF19514 (type I and IV) anagrelide / BL-4162A (Agrylin^®, Xagrid^®, Thromboreductin^®) => 2-amino-5,6-dichloro-3,4-dihydroquinazoline / RL603 9-(tetrahydro-2-furyl) adenine
	PDE4A PDE4B PDE4C PDE4D			cilomilast (Amiflo^®) roflumilast imidazo[1,2-a]quinoxalines^ref
	PDE5A			sildenafil citrate (Revatio^®, Viagra^®, Vigrex^®) (strong inhibitor) tadalafil (Cialis^®) vardenafil (Levitra^®, Nuviva^®) DA-8159
	PDE6A (photoreceptors)			sildenafil citrate (Viagra^®, Vigrex^®) (weak inhibitor)
nucleotide metabolism	hypoxanthine/guanine phosphoribosyltransferase (HGPRT / HPRT) 1 2
	thymidine kinase 1 (TK1) (soluble) 2 (TK2) (mitochondrial)
	deoxyguanosine kinase
	deoxycytosine kinase
	dihydrofolate reductase (DHFR)			methotrexate (MTX) / amethopterin sodium (Folex^©, Mexate^©, Methotrexate^®, Rheumatrex^©, ...) aminopterin sodium (Aminopterin Sodium^©) edatrexate / 10-ethyl,10-deaza aminopterin lometrexol pralatrexate (PDX) (Folotyn^©; source : Allos Therapeutics, Inc.) was rationally designed for improved transport into tumor cells via the reduced folate carrier (RFC-1), and greater intracellular drug retention raltitrexed / ZD1694 (Tomudex^©) : intracellularly is polyglutamated to its active form which can be retained in cells for prolonged periods. pemetrexed / multitargeted antifolate (MTA) / LY231514 (Alimta^©) for NSCLC , malignant mesothelioma , and other solid tumors trimetrexate (Neutrexin^©)
	adenosine deaminase (ADA)			tacrine (Cognex^©) pentostatin / 2'-deoxycoformycin (Nipent^©) cladribrine / 2-chlorodeoxyadenosine (2-CdA) (Leustatin^©) fludarabine (Fludara^©) erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA)
	xanthine oxidase (homodimer; converted to xanthine oxidase by irreversible proteolytic modification or reversible thiol oxidation)			allopurinol (Allgoric^©, Allorin^©, Cyploric^©, Lopurin^©, Zyloric^©, Zyloprim^©) => oxypurinol febuxostat / TMX-67
	ribonucleotide reductase M1 M2 M2B			hydroxyurea / hydroxycarbamide (Hydrea^©, Oncocarbide^©) didox / 3,4-dihydroxybenzohydroxamic acid trimidox / 3,4,5-trihydroxybenzamidoxime
DNA topoisomerases	DNA topoisomerase I / Scl-70			camptothecin derivatives topotecan (Hycamtin^©) irinotecan / CPT-11 (Camptosar^©) => SN-38 DTS-108 => SN-38 9-nitrocamptothecin (9NC) 9-aminocamptothecin (9-AC) 10,11- methylenedioxycamptothecin chimmitecan
DNA topoisomerases	DNA topoisomerase II / DNA girase (p170^a or p180^b)			epipodophyllotoxins (synthetic analog of podophyllotoxin ) teniposide / VM-26 (Vumon^©) etoposide / VP-16-213 (Vepesid^©, Toposar^©, Etopophos^©) podophyllin podofilox (Condylox^®) actinomycin D / dactinomycin (antibiotic) (Cosmegen^©) ICRF-154 ICRF-193 bleomycin (antibiotic) sulfate (Blenoxane^©) acutissimin A lucanthone acridine derivatives : amsacrine (AMSA PD^©) anthracycline antibiotics : aclacinomycin A (aclarubicin) AD-32 annamycin (liposomal : Aronex^©) carminomycin (Carubicin^©) daunorubicin / daunomycin (DNM) / rubidomycin hydrochloride / NSC-82151 (Cerubidine^©) => daunorubicinol pegylated liposomal daunorubicin (DaunoXome^©) DTS-201 (source : Diatos SA) : reactivation of doxorubicin occurs extracellularly in the tumor through enzymatic cleavage of the peptide by at least two enzymes: CD10 (Neprilysin / CALLA) and Thimet Oligopeptidase (TOP). They produce two intermediate metabolites Ala-Leu-Dox and Leu-Dox which enter stromal and tumor cells and are converted into free doxorubicin hydrochloride / NSC-123127 (Adriamycin^©, Rubex^©, ...; Pharmacia and Upjohn; Peapack, NJ; liposomal doxorubicin / TLC D-99 (Evacet^©) pegylated liposomal doxorubicin (PLD) : Caelyx^©, Doxil^©, Doxilen^©, DOX-SL^©, LipoDox^©, Myocet^©; injections are less cardiomyotoxic ThermoDox^© (source : Celsion Corp.) : is a temperature-sensitive liposomal encapsulation activated by radio frequency ablation (RFA), which allows focused delivery of the drug to the liver tumor lesions 4'-iodo-4'deoxydoxorubicin epirubicin / 4'-epidoxorubicin (Ellence^©, Pharmacia and Upjohn, Portage, MI; Farmorubicin^©) is the only anthracycline able to form glucuronides esorubicin idarubicin (Idamycin^®, Zavedos^®) => idarubicinol mitoxantrone (an anthracenedione) (Novantrone^©) nemorubicin / MMDX pirarubicin can be transformed into doxorubicin itself. pixantrone (BBR 2778) (aza-anthracenedione) sabarubicin / MEN-10755 (the first disaccharide anthracycline) valrubicin (Valstar^©) variamycin B zorubicin (Rubidazone^©) RTA 401 RTA 402 RTA 744 (source : Reata Pharmaceuticals, Inc.) KRN-8602 PNU-159568 pyrromycin musettamycin marcellomycin amonafide (Xanafide^©; source : Antisoma)
histone deacetylase (HD / HDAC)	class I : histone deacetylase 1 (HDAC1) Rpd1 (it binds Sin3 corepressor and Ume6) HDAC2 HDAC8 HDAC11 class II : HDAC4 and HDAC5 HDAC6 HDAC7 HDAC9 HDAC10 class III			HDAC inhibitors (HDIs) : short chain fatty acid sodium butyrate (NaB) phenylbutyrate pivaloyloxymethyl butyrate (Pivanex^©, AN-9) (source : Titan) valproic acid (VPA) (Depakin^©, Depakin Chrono^©, PEAC minitablets^©; source: TopoTarget A/S) second generation HDI : hydroxamic acids : trichostatins trichostatin A (TSA) SAHA and its derivatives vorinostat / suberoylanilide hydroxamic acid (SAHA) / NVP-LAQ824 (unselective) (source : Merck & co) suberic bishydroxamic acid (SBHA) oxamflatin azelaic bishydroxamic acid (ABHA) m-carboxycinnamic acid bis-hydroxamide (CBHA) scriptaid (SB-556629) pyroxamide propenamides aroyl pyrrolyl hydroxyamides amides : MS275 / N-(2-aminophenyl)-4-[N-(pyridin-3-yl-methoxycarbonyl)amino- methyl]benzamide (HDAC1 and HDAC3) MethyGene CI994 (HDAC1 and HDAC3) (source : Pfizer) epoxyketone-containing cyclic tetrapeptides : trapoxins HC-toxin chlamydocin diheteropeptin WF-3161 Cyl-1 and Cyl-2 non-epoxyketone-containing cyclic tetrapeptides : romidepsin / FK228 / bicyclic depsipeptide FR 901228 (source : Gloucester Pharmaceuticals) cyclic-hydroxamic-acid-containing peptides (CHAPs) miscellaneous structures depudecin tubacin organosulfur compounds second generation HDAC inhibitors with the hydroxamate and benzamide head group panobinostat / LAQ824/LBH589 inhibits HDAC6 / tubulin deacetylase (TDAC) (unselective) (source : Novartis) MGCD0103 (source : Pharmion Corporation and MethylGene, Inc) (HDAC1 and HDAC3) belinostat / PXD101 (CuraGen, TopoTarget) NVP-LAQ824 (Novartis) ITF2357 / givinostat (Italfarmaco)
histone deacetylase (HD / HDAC)	SIRT1 / Sir2a	p53	resveratrol
histone acetyltransferase (HAT)	p300 / CBP
	TAF_II250
	GRIP
	GCN5
	PCAF
	pCIP
	SRC-1
	Tip60
ATPases	F₀F₁ ATPase			oligomycin
	myosin ATPase			butanedione monoxime (BDM)
	H⁺/ K⁺ ATPase (a subunit : gastric or nongastric ; b subunit) (lumenal membrane of parietal cells in stomach)			proton pump inhibitors (PPI) : prodrugs activated at pH 1.0 inside the canaliculus of a parietal cell, faster than their serum elimination rate esomeprazole / S-omeprazole (Nexium^®) lansoprazole (Prevacid^®, Zoton^®) binds to cys321, 813 (or 822) and 892 omeprazole (racemic) (Antra^®, Gastroloc^®, Mopral^®, Omepral^®, Losec^®MUPS (Multiple Unit Pellet System) tablets, Prilosec^®) binds covalently to 2 cysteine residues at positions 813 (or 822) and 892 pantoprazole (Protium^®, Protonix^®) binds to cys813 and 822 rabeprazole (Aciphex^®)
	3 Na⁺ / 2 K⁺ ATPase			palytoxin cardiac glycosides (agonists of ouabain-like endogenous factors) : cardenolides : digitoxin (Crystodigin^®) digoxin (Lanoxin^®, Lanoxicaps^®) ==Eggerthella lenta ==> inactive metabolyte oleandrin ouabain 16-formyl-gitoxin methyldigoxin (Lanitop^®) neriifolin gitoxin bufadienolides : bufalin marinobufagenin cinobufagenin
phospholipases	phospholipase A₁ (PS-specific)	removes FA in sn-1 from 1,2- diacylglycero phospholipids
	phospholipase A₂ group I IA (secretory) IB (pancreas) group II IIA (secretory : platelets , synovial fluid) IIB (secretory) IIC (possible pseudogene) IID (secretory) IIE IIF group III group IV (cytosolic, the key players for eicosanoid production) IVA (calcium-dependent translocation to perinuclear membrane) IVB IVC(calcium-independent) group V (secretory) group VI (cytosolic, calcium-independent) group VII (platelet-activating factor acetylhydrolase, plasma) group VIII group IX group X (secretory) group XI group XII group XIII		mellitin mepacrine 4-Br- phenacylbromure	Bi 4-bromophenacylbromide A-002 (1-H-indole-3-glyoxamide, varespladib methyl; Anthera Pharmaceuticals, San Mateo, CA, USA), is a novel selective sPLA₂ inhibitor in human beings with specificity towards sPLA₂-IIA (50% inhibitory concentration [IC₅₀] 9–14 nmol/L), sPLA₂-V 77 nmol/L), and sPLA₂-X (IC₅₀ 15 nmol/L) enzymes^ref
	phospholipase B
	phospholipase Cb (activated by G_qPCRs ; found only in Metazoa) phospholipase Cb₁ (PI-specific) phospholipase Cb₂ phospholipase Cb₃ (PI-specific) phospholipase Cb₄
	phospholipase Cg (activated by RTKs ; found only in Metazoa) phospholipase Cg₁ phospholipase Cg₂ (PI-specific)
	phospholipase Cd1 (activated by Ca²⁺; found only in Metazoa, plants and yeasts, no PH domain ) phospholipase Ce
	PC-specific phospholipase D1 (PC-specific, PI-4,5-P₂ stimulated, oleate inhibited; found in all Eukarya) GPI-specific phospholipase D1 phospholipase D2
ANRP	GrpE
AAP	DnaJ
Ras-like superfamily	Arf family ARF1 ARF2 ARF3 ARF4 ARF5 ARF6 ARFL1 Rap family Rab family Rho family RhoH Rac family Ran family Ras family RAP1A RAP1B RAP2A RAP2B H-RAS K-RAS1 K-RAS2 (a and b isoforms) N-RAS M-RAS R-RAS R-RAS2 / TC21 R-RAS3 RALA RALB RHEB1 RHEB2			TAT-C3
GNRP / GEF / GDS	Dbl TIAM1 GRF1 (Ca²⁺-CaM-dependent) GRF2 / Epac / C3G EF-Ts eIF2B eIF2Ba eIF2Bb eIF2Bg eIF2Bd eIF2Be RCC Smg25 SOS1 VAV1 VAV2 VAV3
GAP	Rho/Rac GAP RhoGAP1 / p50 RhoGAP4 / p115 RhoGAP5 / p190 RhoGAP6 (5 isoforms) chimerin 1 / n-chimaerin chimerin 2 / b chimaerin Rap1-GAP RASA1 / p120^GAP RASA2 / RasGAP 2 IQGAP-1 NF1 / neurofibromin 1 IRA1 IRA2	Rho, Rac Rho Rho Rho RhoA Rac Rac Rap1 Ras Ras Ras Ras Ras Ras
GEF & GAP	BCR (also Ser/Thr kinase)	Rho / Rac
GDI	RhoGDIa	Rho
	RhoGDIb
	RhoGDIg


membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG)	fatty acid cyclooxygenase (COX) => PGH synthase (PGHS) 1 (active site : Val; monotopically inserted in the ER and nuclear membrane with the substrate-binding pocket precisely orientated to take up released arachidonic acid, constitutive) COX-1 (GI tract, kidney, platelets ) partial COX-1 (PCOX-1) COX-3 (GI tract, heart and aorta) Can form homodimers or heterodimers with COX-2^ref			5,8,11,14-eicosatetraynoic acid nonsteroidal antiinflammatory drugs (NSAIDs) alkanones nabumetone (Relafen^®) tenidap (Enablex^®) azapropazone / apazone (Rheumox^®) propacetamol is a pro-drug of paracetamol and was available in a parenteral form for many years (Pro-Dafalgan^®). 2g propacetamol is hydrolysed to 1g paracetamol salicylates salicylic acid choline (Arthropan^®), magnesium (Magan^®), or both (Buf-Puf^®, Trilisate^®, ...) acetylsalicylic acid (ASA) (irreversible inhibitor by covalently acetylating Ser⁵²⁹) (Ascriptin^®, Aspirin^®, Aspirinetta^®, Aspisevt^®, Cardioaspirin^®, Empirin^®, Ecotrin^®, Entrophen^®, Genuine Bayer^®, Halfprin^®; Aggrenox^® in combination with dipyridamole ; Talwin Compound^® in combination with pentazocine ; Percodan^®, ... in combination with oxycodone ) lysine acetylsalicylate (Aspegic^®, Aspidol^®, Cardirene^®, Flectadol^®) : less gastrolesive (basic salt) benorilate diflunisal (Dolobid^®) mesalamine / 5-aminosalicylic acid (Asacol^®, Claversal^®, Salofalk^®, Salofalk^® Granu-Stix^®, Pentacol^®, Pentasa^®, Rowasa^®) methyl salicylate olsalazine (Dipentum^®) : 2 molecules of mesalamine bound together with an azo bond salsalate / salicylsalicylic acid (Disalcid^®, Salflex^®) sulfasalazine / salicylazosulfapyridine choline magnesium trisalicylate (Trilisate^®) acetic acids phenylacetic acids alclofenac (Prinalgin^®) diclofenac (Cataflam^®, Voltarin^®, Voltarin-XR^®, Voltaren^®, Arthrotec^®(together with misoprostol )) fenclofenac / 2-(2,4-dichlorophenoxy) phenylacetic acid (Flenac^®) tolmetin (Tolectin^®) ketorolac (Acular^®, Lixidol^®, Toradol^® or 3 mg nasal spray / ROX-888) carbo- and heterocyclic acermetacin (Emflex^®) etodolac (Lodine^®, Lodine XL^®) indometacine / indomethacin (Imet^®, Indocid^®, Indocin^®, Indocollirio^®, Indom^®, Indoxen^®, Indoxen forte^®, Liometacen^®, Metacen^®; Difmetre^®, Difmetre mite^® in combination with caffeine and prochloperazine) oxaprozin (Daypro^®) sulindac (Clinoril^®) propionic acids benoxaprofen (Bexopron^®) carprofen (Rimadyl^®) dexibuprofen (Seractil^®) fenbufen (Cinopal^®) fenoprofen (Nalfon^®) flurbiprofen (Ansaid^®, Ocufen^®) ibuprofen (Advil^®, Buscofen^®, Brufen^®, Ibifon^®, Ibren^®, Ibuphil^®, Ibuprin^®, Ibuprohm^®, Iburam^®, Ibu-tab^®, Ibutop^®, Motrin^®, Moment^®, Neocybalgin^®, Nuprin^®, Cibalginadue^®) indobufen (Ibustrin^®) ketoprofen (Fastumgel^®, Orudis^®, Oruvail^®) naproxen (Aleve^®, Anaprox^®, Naprosyn^®; Trexima^® in combination with sumatriptan ) oxaprozin (Daypro^®) pirprofen suprofen (Profenal^®) tiaprofenic acid (Surgaml^®) fenamates / N-phenylanthranilic acids flufenamic acid meclofenamic acid (Arquell^®, Movens^®) mefenamic acid (Ponstel^®) pyrazolones aminopyrine => ampyrone antipyrine (Auralgan^® in combination with benzocaine) dipyrone / methamizole (Novalgina^®) oxyphenbutazone (Tandearil^®) phenylbutazone (Alindor^®, Alkabutazona^®, Alqoverin^®, Anerval^®, Anpuzone^®, Antadol^®, Anuspiramin^®, Arthrizin^®, Artrizin^®, Artrizone^®, Artropan^®, Azdid^®, Azobutil^®, Benzone^®, Betazed^®, Bizolin 200^®, B.T.Z.^®, Butacote^®, Butacompren^®, Butadion^®, Butadiona^®, Butadione^®, Butagesic^®, Butalgina^®, Butalan^®, Butalidon^®, Butaluy^®, Butaphen^®, Buta-Phen^®, Butapirazol^®, Butapyrazole^®, Butarecbon^®, Butartril^®, Butartrina^®, Butazina^®, Butazolidin^®, Butazolidine^®, Butazona^®, Butazone^®, Butidiona^®, Butiwas-simple^®, Butone^®, Butoz^®, Butylpyrin^®, Buvetzone^®, Buzon^®, Chembutazone^®, Digibutina^®, Diossidone^®, Diozol^®, Diphebuzol^®, Diphenylbutazone^®, Ecobutazone^®, Elmedal^®, Equi Bute^®, Eributazone^®, Esteve^®, Febuzina^®, Fenartil^®, Fenibutasan^®, Fenibutazona^®, Fenilbutazona^®, Fenylbutazon^®, Fenilbutina^®, Fenilbutine^®, Fenibutol^®, Fenilidina^®, Fenotone^®, Flexazone ^®, G 13,871^®, IA-But^®, Intalbut^®, Intrabutazone^®, Ipsoflame^®, Kadol^®, Lingel^®, Malgesic^®, Mephabutazone^®, Merizone^®, Nadazone^®, Nadozone^®, Neo-Zoline^®, Novo-phenyl^®, Phebuzin^®, Phebuzine^®, Phen-Buta-Vet^®, Phenbutazol^®, Phenopyrine^®, Phenylbetazone^®, Phenylbutaz^®, Phenylbutazonum^®, Phenyl-mobuzon^®, Pirarreumol B^®, Praecirheumin^®, Pyrabutol^®, Pyrazolidin^®, Rectofasa^®, Reudo^®, Reudox^®, Reumasyl^®, Reumazin^®, Reumazol^®, Reumune^®, Reupolar^®, Robizon-V^®, Rubatone^®, Scanbutazone^®, Schemergin^®, Shigrodin^®, Tazone^®, Tetnor^®, Tevcodyne^®, Therazone^®, Ticinil^®, Todalgil^®, Uzone^®, VAC-10^®, Wescozone^®, Zolaphen^®, Zolidinum^®,) propyphenazone / propifenazone / 4-isopropylantipyrine / isopropylphenazone (Cistalgan^® in combination with flavoxate ) enolic acids oxicam ampiroxicam cinnoxicam (Sinartrol^®) droxicam isoxicam lornoxicam (Xefo^®) meloxicam (the one with the lowest COX-2 IC₅₀ / COX-1 IC₅₀ rate, so usable as a COX-2 selective inhibitor) (Mobic^®) piroxicam (Feldene^®) pivoxicam sudoxicam tenoxicam (Tobitil^®) COX-inhibiting nitric oxide-donating (CINOD)
	fatty acid cyclooxygenase 2 (COX2) / PGH synthase 2 (PGHS2) (active site : Ile; monotopically inserted in the ER and nuclear membrane with the larger substrate-binding pocket precisely orientated to take up released arachidonic acid) => COX-2b (inducible) COX-2 (constitutive : macula densa, thick ascending limb of Henle loop, podocytes, interstitial papillary cells of kidneys, certain brain regions => involved in renal water and electrolyte balance, gastric cytoprotection, and platelet aggregation) COX-2 (inducible by various inflammatory insults in monocytes or mast cells or by shear stress in endothelium) Can form homodimers or heterodimers with COX-1^ref			COX-1 antagonists acetanilide => p-aminophenol => phenacetin / acetophenetidin => acetaminophen / paracetamol / N-acetyl-p-aminophenol^ref (Acetanol^®, Liquiprin^®, Panadol^®, Tachipirina^®, Tylenol^®; Perfalgan^®i.v.; Talcen^® in combination with pentazocine ; Percocet^® and Tylox^® in combination with oxycodone ; Co-efferalgan^® and Tachidol^®in combination with codeine ; Mersyndol^® in combination with codeine and doxylamine; Algosil^®, Antinevralgico Knapp^®, Antireumina^®, Drin^®, Neocibelgina^®, Neonevral^®, Neonisidina^®, Verdal^® in combination with acetylsalicylic acid and caffeine) (on COX-2b only: antipyretic but not antiinflammatory as WBC-derived peroxides inhibit it) NS-398 DFP [3-(2-propyloxy) -(4-methyl-sulphonylphenyl)- (5,5-dimethyl)-furanone] COX-2 selective inhibitors (CSI) block the cyclooxygenase activity of PGHS2, but do not affect the associated peroxidase function sulfonanilides nimesulide (Aulin^®) SC-58125 / SC-57666 BF-389 L743337 flosulide indole acetic acids etodolac (Lodine^®) coxibs : 1^st generation coxibs : diaryl-substituted pyrazoles celecoxib (Celebrex^®) OSU03012 diaryl-substituted furanones rofecoxib (Arofexx^®, Vioxx^®) 2^nd generation coxibs : valdecoxib (Bextra^®) etoricoxib (Arcoxia^®, Tauxib^®)^{ref1, ref2} : its long plasma half-life allows for once-daily oral dosing; the highest recommended daily dose for chronic use is 90 mg for rheumatoid arthritis and 60 mg for osteoarthritis and chronic low back pain. The recommended daily dose for acute pain relief treatment from primary dysmenorrhea and acute gouty arthritis is 120 mg; same efficacy as non-COX-2 selective NSAID, with fewer gastro-intestinal adverse effects deracoxib (Deramaxx^®) lumiracoxib (Prexige^®) COX-inhibiting nitric oxide-donating (CINOD)
	PGD₂ synthase / PGH₂ isomerase (hematopoietic)
	PGD₂ synthase / PGH₂ isomerase (brain)
	a-ketoreductase, family 1, member C3 / PGF_2a synthase (uterus)
	microsomal PGE₂ synthase (mPGES) / PGH₂ isomerase
	15-hydroprostaglandin dehydrogenase
	thromboxane A₂ synthase (platelets , macrophages, lung, spleen)			dazoxiben ozagrel (OKY-046, (E)-3-(4-(1-imidazolylmethyl)phenyl)-2-propenoic acid) ridrogrel trapidil BM-567 (N-pentyl-N'-[(2- cyclohexylamino-5-nitrobenzene) sulfonyl]urea) picotamide (N,N'bis(3-pyridinylmethyl)-4-methoxy-isophthalamide) (Plactidil^®)
	prostacycline synthase (endothelial cells, lung, spleen)
	arachidonate 5-lipoxygenase (5-LO / 5-LOX) / LTA₄ synthase (nonheme iron dioxygenase; with Ca²⁺ and ATP translocates to the nuclear envelope from either the nuclear or cytoplasmic compartment. FLAP, a small resident nuclear envelope integral protein, acts as an apparent arachidonic acid transfer protein and facilitates presentation (WBCs : mast cell, macrophage, ...)	arachidonic acid => LTA₄		zileuton (Zyflo^®) boswellic acid esculetin 5,8,11,14-eicosatetraynoic acid w-3 fatty acids (OmegaBrite^®, Fisol^®) eicosapentanoic acid (EPA) docosahexanoic acid (DHA) octadecatetraenoic acid
	5-LOX-activating protein (FLAP)			MK-886
	arachidonate 8-lipoxygenase (8-LOX)			5,8,11,14-eicosatetraynoic acid
	arachidonate 12-lipoxygenase (12-LOX) (platelets , WBCs)			5,8,11,14-eicosatetraynoic acid
	arachidonate 15-lipoxygenase (15-LOX)			5,8,11,14-eicosatetraynoic acid
	LTA₄hydrolase (LTA₄H) (a catalytic domain highly related to thermolysin and a COOH-terminal domain with armadillo-like repeats points to an interesting evolutionary heritage : because LTA₄H is found in yeast, predating the appearance of other leukotriene biosynthetic enzymes, it may have had, at one time, exclusively aminopeptidase or other noneicosanoid related functions)	LTA₄ => LTB₄		SC57461A bestatin
	LTB₄12-hydrodehydrogenase
	LTC₄ synthase (a FLAP-like protein found in the nuclear envelope)	LTA₄ => LTC₄		MK0591
	MGST2
	MGST3
	g-glutamyl- transpeptidase (gGT) 1 (in Mus musculus g-glutamyl leukotrienase (GGLT) / g-glutamyltransferase-like activity 1)	LTC₄ => LTD₄		acivicin
	g-glutamyl- transpeptidase (gGT) 2
	GGTLA1
	GGTLAL1
	glutathione synthase glutathione S-transferase (GST) : m1 (GSTM1) t1 (GSTT1) p1 (GSTP1)			buthionine-(S,R)-sulfoximine (BSO)
neurotrasmitter anabolism	indoleamine 2,3-dioxygenase (IDO)	Trp		1-methyltryptophan (1-MT) indoximod
	tryptophan 3-monooxygenase a b d e g h q z In mice 2 isoforms of typtophan hydroxylase-2 (Tph2), an enzyme that governs the manufacture of serotonin, exist : serotonin levels differ by 50-70% between animals with one or other of the variants
	tyrosine hydroxylase	Tyr => DOPA		a-methyltyrosine / metyrosine (Demser^®)
	aromatic L-amino acid decarboxylase (DOPA decarboxylase)	DOPA => DA 5-hydroxytryptophan (oxitriptan (5-HTP) (Levotonine^®, Pretonine^®, Serotonyl^®, Triptene^®) => 5-HT		DOPA decarboxylase inhibitors (DDI) : carbiDOPA (Lodosyn^®; in combination with L-DOPA in Atamet^®, Sinemet^®, Sinemet CR^®) ; benserazide (+ L-DOPA = Madopar^®) L-a-methylDOPA (competitive inhibitor)
	histidine decarboxylase	His => histamine		a-fluoromethylhistamine (irreversible inhibitor)
	histamine-N-methyltransferase (HMT)	histamine		metoprine
neurotransmitter catabolism	acetylcholinesterase (AChE)	ACh => acetate + choline	neurons, erythrocytes	acetylcholinesterase inhibitors (AChEIs) : onchidal fasciculins huperzine A tacrine 1,5-bis(4-allyldimethylammoniumphenyl)pentan-3-one dibromide (BW284c51) noncovalent inhibitors : edrophonium chloride (Tensilon^®, Enlon^®, Reversol^®, ...) tacrine / 1,2,3,4-tetrahydro-9-aminoacridine (Cognex^®) donepezil (Aricept^®) "reversible" carbamate inhibitors eserine / physostigmine salicylate (Antilirium^®) or sulfate phenserine neostigmine bromide or methylsulfate (Prostigmin^®) pyridostigmine bromide oral (Mestinon^®) or parenteral (Regonol^®, Mestinon^®) demecarium bromide (Humorsol^®) galantamine (Nivalin^®, Razadyne^®, Reminyl^®) rivastigmine (Exelon^®, Excelon^®) carbamate insecticides aldicarb (Temik^®) bendiocarb (Dycarb^®, Trumpet^®) carbaryl (Sevin^®) carbofuran dimetilan isolan methiocarb (Draza^®, Bayer UK892^®) methomyl pirimicarb (Aphox^®, Pirimor^®, Rapid^®) propoxur (Baygon^®) organophosphorus group A, X = halogen, cyanide, or thiocyanate leaving group diisopropyl fluorophosphate (DFP), isofluorophate nerve gases of the G series tabun (GA) / ethyl N-dimethyl phosphoramidocyanidate sarin (GB) / O-isopropyl methylphosphonofluoridate soman (GD) / pinacolyl methylphosphonofluoridate GE cyclohexyl sarin (GF) group B, X = alkylthio, arylthio, alkoxy, or aryloxy leaving group paraoxon / E 600 / O,O-diethyl O-(4-nitrophenyl)-phosphate (Mintacol^®) malaoxon / O,O-dimethyl S-(1,2-dicarboxyethyl)- phosphorothioate metrifonate => dimethyl 2,2-dichlorovinyl phosphate (DDVP) pirimiphos-methyl (Actellic D^®, Actellic 2% dust^®) nerve gases of the V series VE VG V-Gas VM VX / O-ethyl S-(2-diisopropyl aminoethyl) methylphosphonothiolate : absorbed through skin, 99% is degraded within 15 hours on concrete due to very high pH group C, thionophosphorus or thio-thionophosphorus compounds phosphorothioate insecticides parathion / O,O-diethyl O-(4-nitrophenyl)- phosphorothionate (Etilon^®) => paraoxon methyl parathion malathion / O,O-dimethyl S- (1,2-dicarbethoxyethyl) -phosphorothionate (Chemathion^®, Fyfanon^®, Mala-Spray^®, Malathion^®, Prioderm^®) => malaoxon diazinon / dimpylate / O,O-diethyl O-(2-isopropyl-6-methyl -4-pyridinyl)-phosphorothionate (Diazinon^®, Knox-out^®, Spectracide^®) chlorpyrifos / O,O-diethyl O-(3,5,6-trichloro-2 -pyridyl) -phosphorothionate (Dursban^®, Lorsban^®) chlorpyrifos-methyl (Reldan 22^®, Greencrop^®, Storeclean^®) phosphamidon monocrotophos disulphoton phorate dichlorvos (DDVP^®, Vapona^®, Vaponite^®) dithiophosphorus compounds dimethoate (Cygon^®, De-Fend^®, Rogor^®) group D, pyrophosphates and similar compounds tetraethyl pyrophosphate (TEPP) (Kilmite-40^®, Tetron^®, Vapotone^®) group E, quaternary ammonium compounds echothiophate / MI-217 / diethoxyphosphinylthiocholine iodide (Phospholine Iodide^®) azinphos-methyl bromophos-ethyl bromophos carbophenothion chlorphenvinphos cythioate demeton-S-methyl fenitrothion fenthion (Lebaycid^®) formothion heptenophos jodphenphos (iodofenphos) mevinphos phorate phosmet phoxim reactivators hydroxylamine hydroxamic acids oximes pyridine-2-aldoxime methyl chloride (2-PAM) / pralidoxime chloride (Protopam Chloride^®) pralidoxime methylsulfate (Contrathion^®) obidoxime (Toxogonin^®) HI-6 nostocarboline
	MAO-A (in outer membranes of mitochondria of noradrenergic and dopaminergic CNS neurons, cardiomyocytes, hepatocytes, enterocytes, muscularis mucosae and muscular layers of duodenum, endothelial cells of lymphatic vessels, muscular layers and fibroblasts of arteries and veins, renal tubuli, collecting ducts and the Bowman's capsule)	DA NE 5-HT		irreversible ("classical") MAO inhibitors (MAOI) (bind to FAD site) acetylenic agents / methylbenzylpropinylamine clorgyline pargyline (Eutonyl^®, Eudatine^®, Tenalin^®, Paxil^®, Seroxat^®, Aropax^®, Deroxat^®) rasagiline (Azilect^®) hydrazines benmoxine (Neuralex^®, Nerusil^®) brofaromine isocarboxazide (Marplan^®, Enerzer^®, Marplon^®) iproniazid (Marsilid^®, Iprozid^®, Ipronid^®, Rivivol^®, Propilniazida^®) iproclozide (Sursum^®) mebanazine (Actomol^®) nialamide (Niamid^®, Espril^®, Isalizina^®, Surgex^®) phenelzine (Nardil^®, Stinerval^®, Monofen^®, Fenelzin^®, Kalgan^®, Nardelzine^®) pheniprazine phenoxypropazine (Drazine^®) indolalkylamine etryptamine (Monase^®) phenylcyclopropylamine tranylcypromine (Parnate^®, Parmodalin^®, Sicoton^®, Transamin^®, Transapin^®, Tylciprine^®) pyrimidine safrazine (Safra^®) reversible inhibitors of MAO (RIMA) benzamide derivatives moclobemide (Aurorix^®, Manerix^®, Moclamine^®) benzoxazine caroxazone methylphenethylamine amiflamine oxazolidinone cimoxatone toloxatone (Humory, Perenum^®) piperidine brofaromine (Consonar^®) pyrazino carbazole pyrazidole / pirlindole pyrazino-indole tetracyclic tetrindole (a tetracyclic antidepressant) incazane
	MAO-B (in mitochondria of serotonergic neurons, cardiomyocytes, hepatocytes, enterocytes, muscularis mucosae and muscular layers of duodenum, muscular layers and fibroblasts of arteries and veins, renal tubuli, platelets )	phenethylamines		selegiline / l-deprenyl (Eldepryl^®, Carbex^®, Atapryl^®, Lesotal^®, Eldeprine^®, Movergan^®, Jumex^®, Jumexal^®, Plurimen^®) phenelzine (Nardil^®, Stinerval^®, Monofen^®, Fenelzin^®, Kalgan^®, Nardelzine^®) nialamide (Niamid^®, Espril^®, Isalizina^®, Surgex^®) tranylcypromine (Parnate^®, Parmodalin^®, Sicoton^®, Transamin^®, Transapin^®, Tylciprine^®)
	catechol-O- methyltransferase (COMT)	L-DOPA => 3-O-methyldopa (3-OMD)		tolcapone (Tasmar^®) entacapone (Comtan^®, Comtess^®)
	GABA transaminase (GAT)			vigabatrin / g-vinyl-GABA (Sabril^®) valproic acid / n-dipropyl acetate (Depakene^®, Convulex^®, Depakine^®, Depalept^®, Epilim^®, Ergenyl^®, Leptilan^®, Orfiril^®, Valporal^®) or valproate (Depakote^®, Epival^®, Elvetium^®, Everiden^®, Novoseven^®, Valcote^®, Valnar^®) or sodium valproate (Depacon^®, Valpro^®)
	succinate semialdehyde dehydrogenase (SSAD)			valproic acid / n-dipropyl acetate (Depakene^®, Convulex^®, Depakine^®, Depalept^®, Epilim^®, Ergenyl^®, Leptilan^®, Orfiril^®, Valporal^®) or valproate (Depakote^®, Epival^®, Elvetium^®, Everiden^®, Novoseven^®, Valcote^®, Valnar^®) or sodium valproate (Depacon^®, Valpro^®)
	fatty acid aminohydrolase (FAAH)			phenylmethylsulfonyl fluoride methyl-arachidonoyl fluorophosphonate
	dipeptidyl-dipeptidase (DAP) / CD10 / CALLA / neutral endopeptidase (NEP) / enkephalinase / neprilysin	b-amyloid		thiophan (N-(a-benzyl-b-thio-propionyl)glycine) vasopeptidase inhibitors (VPI) candoxatril acetorphan / racecadotril LAF237 NN7201 P93/01 talabostat mesylate (PT-100), the amino boronic dipeptide Val-boro-Pro^ref
	a-glucosidase		intestinal epithelial cells	acarbose (Glucobay^®, Precose^®) miglitol (Glyset^®)
	serine proteases (including tryptase, amylase and phospholipase A₂ in pancreatic juice)			6- (or e-) aminocaproic acid (ACA) (Amicar^®) tranexamic acid (TA) (Cyclocapron^®, Cyclokapron^®, Tranex^®, Transamin^®, Ugurol^®) aprotinin / bovine pancreatic trypsin inhibitor (BPTI) camostat mesilate (CM) / FOY-305 (p.o.) gabexate mesilate nafamostat mesilate sepimostat mesilate ulinastatin
chymase 1	mast cells	angiotensinogen angiotensin I
prorenin / big renin => renin	juxtaglomerular cells (JGC) in the walls of afferent arterioles of renal glomeruli when ... increased NaCl reapsorption in the proximal tubule (decreased pressure natriuresis) => decreased tubular delivery of Cl^- to macula densa => upregulation of nNOS => peroxynitrite activates COX-2 => PGs activate JGC drop in blood pressure in afferent arteriole => stretch-activated ion channels in JGC orthosympathetic system activates b₁-ARs on JGC	angiotensinogen synthetic tetradecapeptide renin substrate (TDP; Asp-arg-val-tyr-ile-his-pro-phe-his-leu-leu-val-tyr-ser)		renin binding protein (RBP) aliskiren / SPP100 (Rasilez^®, Tekturna^®) remikiren enalkiren pepstratin A
angiotensin I-converting enzyme (ACE) / kininase II / dipeptidyl carboxypeptidase / CD143 : ACE also has a GPI-anchored protein releasing activity (GPIase activity). Unlike its peptidase activity, GPIase activity is weakly inhibited by the tightly binding ACEI and not inactivated by substitutions of core amino acid residues for the peptidase activity, suggesting that the active site elements for GPIase differ from those for peptidase activity. ACE shed various GPI-anchored proteins from the cell surface, and the process was accelerated by the lipid raft disruptor filipin. The released products carried portions of the GPI anchor, indicating cleavage within the GPI moiety. Further analysis by HPLC-MS predicted the cleavage site at the mannose-mannose linkage. GPI-anchored proteins such as TESP5 and PH-20 were released from the sperm membrane of wild-type mice but not in Ace knockout sperm in vivo. Moreover, peptidase-inactivated E414D mutant ACE and also PI-PLC rescued the egg-binding deficiency of Ace knockout sperms, implying that ACE plays a crucial role in fertilization through this activity^ref.	somatic isozyme : endothelial cells of lung capillaries testis-specific isozyme : developing spermatids and mature sperm	angiotensin I => angiotensin II BK substance P		ACE inhibitors (ACEI) : prodrug (drug) : -pril (-prilat) sulphydrylic ACEIs alacepril (Cetapril^®) altiopril calcium / MC-838 captopril (Capoten^®) zofenopril (Zofenil^®, Zoprace^®; Zopranol^®, long-lasting action) carboxylic ACEIs benazepril (Lotensin^®) (benazeprilat) cilazapril (Inhibace^®) delapril hydrochloride (Adecut^®) enalapril (Vasotec^®) (enalaprilat) (Vasotec Injection^®) lisinopril (Prinivil^®, Zestril^®; Zestoretic^® in combination with hydrochlorothiazide moexipril (Univasc^®) (moexiprilat) perindopril (Aceon^®) (perindoprilat) quinapril (Accupril^®) (quinaprilat) ramipril (Altace^®, Quark^®) (ramiprilat) spirapril (Renomax^®) (spiraprilat) trandolapril (Mavik^®, Odrik^®) stiff lactamic cilazopril (cilazoprilat) phosphorylic ACEIs : ceranapril fosinopril sodium (Monopril^®) monomamide cyclomethylenic ACEIs idropril imidapril hydrochloride (Tanatril^®) temocapril hydrochloride (Acecol^®) vasopeptidase inhibitors (VPI) inhibit both ACE and neutral endopeptidase (NEP)-24.11, further reduce BK metabolism and increase vasodilator natriuretic peptides and thus may have better cardioprotective effects than ACEI : gemopatrilat omapatrilat / BMS-186716 (Vanlev^®) sampatrilat / UK 81252 fasidotril
ACE2	renal and cardiovascular tissues (including arterial and venous endothelial cells), surface of cells in the lung, gastrointestinal system (ileum, duodenum, jejunum, caecum and colon)	angiotensin I => angiotensin II
	g-glutamyl carboxylase	Glu => g-carboxy-Glu / Gla (Ca²⁺-chelating) osteocalcin factor II factor VII factor IX factor X GAS6 matrix Gla protein protein C protein S protein Z PRGP1 PRGP2 TMG3 TMG4		vitamin K analogues that inhibit 2,3-epoxide reductase activity : 4-hydroxycoumarin derivatives : acenocoumarol / nicoumalone (Sinthrome^®, Sintron^®, Sintrom^®) phenprocoumon (Marcumar^®) dicumarol / bishydroxycoumarin warfarin sodium (Aldocumar^®, Coumadin^®, Panwarfin^®, Warfilone^®) : p.o., i.v. indan-1,3-dione derivatives : anisindione (Miradon^®) phenindione (Dindevan^®, Pindione^®) rodenticides (agents of accidental or intentional poisoning) bromadiolone brodifacoum chlorophacinone (Rogar X^®) diphacin diphenadione dicoumeral fumarin pindone pival racuman ratafin rodefin tomorin 0.25% warfarin
	prekallikrein ==factor XIIa==> kallikrein B / Fletcher factor (plasma)			aprotinin (Trasylol^®) ecallantide / DX-88 (source : Dyax)
	kallikrein 1 (renal / pancreatic / salivary)
	kallikrein 2 (prostate)
	kallikrein 3 / PSA (prostate)
	kallikrein 4 (prostate / enamel matrix)
	kallikrein 5
	kallikrein 6
	kallikrein 7
	kallikrein 8
	kallikrein 9
	kallikrein 10
	kallikrein 11
	kallikrein 12
	kallikrein 13
	kallikrein 14
	kallikrein 15
heme oxygenase	heme oxygenase 1 (HO-1) / hsp32 (inducible)		curcumin (up-regulates expression) caffeic acid phenethyl ester (CAPE) (up-regulates gene expression)	Zn-(II)-protoporphyrin (ZnPP)
	heme oxygenase 2 (HO-2) (constitutive)
	heme oxygenase 3 (HO-3) (in Rattus norvegicus, constitutive)
	carbonic anhydrase I
	carbonic anhydrase II (cytoplasmic kidney)			-zolamides : acetazolamide (Diamax^®, Diamox^®) dichlorphenamide (Daranide^®) methazolamide (Neptazane^®) dorzolamide hydrochloride (Trusopt^®) brinzolamide (Azopt^®)
	carbonic anhydrase III
	carbonic anhydrase IV (lumenal and basolateral membranes of pulmonary (and certain other) capillaries and of proximal renal tubules)
	carbonic anhydrase V
	carbonic anhydrase VI
	carbonic anhydrase VII
	carbonic anhydrase VIII
	carbonic anhydrase IX
	carbonic anhydrase X
	carbonic anhydrase XI
	carbonic anhydrase XII (kidney, colon, pancreas)
	thyroid peroxidase (TPo) (thyroid)			thioureylenes / thionamides: thiouracil 6-methyl-2-thiouracil 6-n-propylthiouracil (PTU) (Mercazole^®, Thyrozole^®, Propycil^®, PTU^®) methimazole / 1-methyl-2-mercaptoimidazole (MMI) (Tapazole^®) carbimazole (Neo-Mercazole^®)
	type 1 5a-reductase (neutral to basic pH optimum; not detectable in the fetus, transiently expressed in newborn skin and scalp, permanently expressed in skin (sebaceous glands) from the time of puberty)	testosterone => dihydrotestosterone (DHT)		finasteride (Propecia^®, Proscar^®) (high doses)
	type 2 5a-reductase (transiently expressed in skin and scalp of newborns, predominant isozyme detectable in fetal genital skin, in male accessory sex organs, and in the prostate)	testosterone => dihydrotestosterone (DHT)		finasteride (Propecia^®, Proscar^®) (low doses)
	3b-hydroxysteroid dehydrogenase (HSD3B) HSD3B1 HSD3B2(adrenal glands and gonads) HSD3B7	pregnenolone => progesterone		trilostane
	11b-hydroxysteroid dehydrogenase HSD11B1 [liver, brain, adipose tissue, lung, and other glucocorticoid-target tissues] HSD11B2	inactive cortisone => active cortisol active aldosterone => inactive 11-keto derivative active cortisol => inactive cortisone		glycyrrhizic acid / glycyrrhizin glycyrrhetic acid (GA) Lydia E. Pinkham's Vegetable Compound carbenoxolone (Biogastrone^®, Bioplex^®, Bioral^®, Sanodin^®) chewing tobacco
	17b-hydroxysteroid dehydrogenase HSD17B1 HSD17B2 HSD17B3 (testes) HSD17B4 HSD17B5 / type II 3a-HSD HSD17B7 HSD17B8
	d-aminolevulinate dehydratase			lead (Pb)
	ferrochelatase			lead (Pb)
	alcohol dehydrogenase (ADH) class I : homo- or heterodimers of the following subunits a b g class I : homodimer of p class III : homodimer of c class IV : homodimer of m/d class V : homodimer of m/d	ethanol = 100 methanol		4-methylpyrazole / fomepizole (Antizol^®)
	aldehyde dehydrogenase (AlDH) family 1 A1 A2 A3 B1 family 2 (mitochondrial) family 3 A1 A2 B1 B2 family 4 : A1 family 5 : A1 family 6 : A1 family 7 : A1 family 8 : A1 family 9 : A1			calcium carbimide (Dipsan^®, Temposil^®) calcium cyanamide disulfiram / tetraethylthiuram disulfide (Antabuse^®, Alcophobin^®, Anticol^®, Aversan^®, Etiltoxdivalproex sodium ) : several active metabolytes of the drug, especially diethylthiomethylcarbamate diethylaminobenzaldehyde (DAEB) chloramphenicol
	aconitase 1 (soluble)			sodium fluoroacetate and fluoracetamide are incorporated into fluoroacetyl-CoA, which condenses with oxaloacetate to form fluorocitrate, the final inhibitor
	aconitase 2 (mitochondrial)
nitric oxide synthase (NOS)	NOS1 / constitutive NOS (cNOS)			aminoguanidine sulfate ; N-iminoethyl-L-lysine ; N^G-methyl-L-arginine (L-NMMA) / L-N^G-nitrosoarginine methyl ester (L-NAME) 6-anilino-5,8-quinolinequinone / LY83583 / LY asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NOS. ADMA inhibits vascular NO production in concentrations found in pathophysiological conditions; ADMA also causes local vasoconstriction when it is infused intraarterially. Thus, elevated ADMA levels may explain the "L-arginine paradox," i.e., the observation that supplementation with exogenous L-arginine improves NO-mediated vascular functions in vivo, although its baseline plasma concentration is about 25-fold higher than the Michaelis-Menten constant K_m of the isolated, purified endothelial NO synthase in vitro. The biochemical and physiological pathways related to ADMA are well understood: dimethylarginines are the result of degradation of methylated proteins; the methyl group is derived from S-adenosylmethionine. Both ADMA and its regioisomer, symmetric dimethylarginine, are eliminated from the body by renal excretion, whereas only ADMA is metabolized via hydrolytic degradation to citrulline and dimethylamine by the enzyme dimethylarginine dimethylaminohydrolase (DDAH). DDAH activity and/or expression may therefore contribute to the pathogenesis of endothelial dysfunction in various diseases. Plasma ADMA levels are increased in humans with hypercholesterolemia, atherosclerosis, hypertension, chronic renal failure, and chronic heart failure. Increased ADMA levels are associated with reduced NO synthesis as assessed by impaired endothelium-dependent vasodilation. In several prospective and cross-sectional studies, ADMA evolved as a marker of cardiovascular risk. With increasing knowledge of the role of ADMA in the pathogenesis of cardiovascular disease, ADMA is becoming a goal for pharmacotherapeutic interventions. Among other potential strategies that are currently being tested, administration of L-arginine has been shown to improve endothelium-dependent vascular functions in subjects with high ADMA levels. Finally, ADMA has gained clinical importance recently because several studies have shown that ADMA is an independent cardiovascular risk factor^ref. L-NNA methylene blue
	NOS2 / inducible NOS (iNOS)
	NOS3 / endothelial NOS (eNOS)
	arginase 1			N^w-hydroxy-L-arginine N^w-hydroxy-nor-L-arginine
suppressor of cytokine signaling (SOCS) / cytokine-induced STAT inhibitor (CIS) / STAT-induced STAT inhibitor (SSI) family (SH2 domain and SOCS box)	SOCS1 SOCS2 SOCS3 SOCS4 / SOCS6 SOCS5 SOCS7 CIS
	thioredoxin			MOL 294
superoxide dismutase (SOD)	SOD1 (soluble, CuZn)			triethylenetetramine (TETA) KCN
	SOD2 (mitochondrial, Mn)
	SOD3 (in Mus musculus, extracellular, CuZn)
Bcl-2 family	antiapoptotic members(group I) : BH4-BH3-BH2-BH1 -TM (~ CED9 in Caenorhabditis elegans) Bcl-2 Bcl-x_L mcl1 Bcl-w Bcl-2A1 / Bfl-1 A1 pro-apoptotic members (~ egl-1 in Caenorhabditis elegans) Group II : BH3-BH2-BH1-TM Bad Bax (a, b, g, and w) Group III : BH3 Bid Bik Bcl-x_S Bim Bak1 Hrk			obatoclax mesylate (GX15-070), a small molecule pan–Bcl-2 family antagonist ABT-199 (Bcl-2-selective)
oteins containing His residues				diethylpyrocarbonate
proteins containing Cys residues				iodoacetamide


*family* (identity > 40%)	*subfamily* (identity > 55%)	*isoform*
		CYP1A1 (up-regulated by AHR )	aromatic compounds
		CYP1A2	aromatic compounds flutamide
		CYP1B1	dioxin
		CYP2A	phenobarbital
		CYP2A6	tegafur
		CYP2A7
		CYP2A13
		CYP2B
		CYP2B6 (up-regulated by VDR )	cyclophosphamide		orphenadrine
		CYP2B7
		CYP2C (Rattus norvegicus)	mephenytoin paclitaxel
		CYP2C8	mephenytoin
		CYP2C9 : 3 SNPs (up-regulated by VDR )	mephenytoin warfarin phenytoin sulfonylureas
		CYP2C18	mephenytoin
		CYP2C19 : 8 SNPs	mephenytoin PPIs
		CYP2D4 (in Mus musculus only)
		CYP2D5 (in Mus musculus only)
		CYP2D6 (in Homo sapiens only) (not inducible !) : ~ 70 SNPs poor metabolizers (PM) intemediate metabolizers (IM) extensive metabolizers (EM) ultrarapid metabolizers (UM)	~ 65 drugs (most abandoned nowadays due to SNPs) : debrisoquine sparteine codeine methadone tyramine tryptamine paroxetine fluoxetine tamoxifen		quinidine SSRIs
		CYP2E1 (in both Homo sapiens and Mus musculus)	ethanol acetaminophen => N-acetyl-p-benzoquinoneimine benzene phenol chlorophorm	lungs
		CYP2F1
		CYP2G1
		CYP2G2
		CYP2J2	arachidonic acid
		CYP2S1
		CYP3A	niphedipine cyclosporine A tacrolimus		troleandomycin
		CYP3A4 (up-regulated by VDR )	60% of clinically prescribed drugs : niphedipine sildenafil macrolides imidazoles HMG-CoA reductase inhibitors HAART fluoxetine fluvoxamine ifosfamide	enterocytes, hepatocytes, kidney	troleandomycin
		CYP3A5	niphedipine
		CYP3A7	niphedipine
		CYP3A43
		CYP4A1 (Mus musculus)
		CYP4A3(Mus musculus)
		CYP4A11
		CYP4B1
		CYP4F2 / LTB₄ w-hydrolase	=> 20-hydroxy-PGs
		CYP4F3 / LTB₄ w-hydrolase	=> 20-hydroxy-PGs
		CYP4F8	=> 19R-hydroxyPGs
		CYP4F11
		CYP4F12
		CYP4X1
		CYP7A1 (rate-limiting enzyme in the neutral bile acid biosynthetic pathway)
		CYP7B1
		CYP8B1 / sterol 12a-hydroxylase
		CYP11A1 / cholesterol 20,22-desmolase / cholesterol side-chain-cleaving enzyme (P450_scc)	cholesterol		aminoglutethimide (Cytadren^©) ketoconazole (Nizoral^®) (at low doses)
		CYP11B1 / 11b-hydroxylase			ketoconazole (Nizoral^®) metyrapone (Metopirone^®)
		CYP11B2 / steroid 11b hydroxylase / 18-hydroxylase			ketoconazole (Nizoral^®)
		CYP17A1 / steroid 17a-hydroxylase / 17,20 lyase			ketoconazole (Nizoral^®) (at low doses) CB7630 / abiraterone acetate
		CYP19 / aromatase	androstenedione testosterone 16 a-hydroxyandrostenedione		aromatase inhibitors (A) : aminoglutethimide (Cytadren^©, Orimeten^®) dexaminoglutethimide YM-511 MK0434 finrozole / MPV-2213ad (source : Hormos Medical Ltd., Turku, Finland) steroidal androstenedione analogs : formestane (Lentaron^®) exemestane (Aromasin^®) imidazole or nonsteroidal structure (NSS)-AI : anastrozole (Arimidex^®) fadrozole / CGS 16949 A (Afema^®) letrozole (Femara^®; source : Novartis) : used in 13 cases as a fertility treatment because it suppresses estrogen and can promote ovulation, it is actually teratogenic and cause miscarriages and should be used only in postmenopausal women with breast cancer vorozole
		CYP21A2 / steroid 21-hydroxylase
		CYP24 / steroid 24-hydroxylase (up-regulated by VDR )	1a,25-(OH)₂-vitamin D₃ => 1a,24R,25-(OH)₃-vitamin D₃ 25-(OH)-vitamin D₃ => 24R,25-(OH)₂-vitamin D₃	inner mitochondrial membrane of proximal convoluted renal tubule cells
		CYP26A1	all-trans retinoic acid
		CYP27A1 / steroid 25-hydroxylase	vitamin D₃ => 25-(OH)-vitamin D₃	hepatocytes	HIV-protease inhibitors
		CYP27B1 / steroid 1a-hydroxylase (down-regulated by VDR )	25-OH-vitamin D₃ => 1a,25-(OH)₂-vitamin D₃	inner mitochondrial membrane of proximal convoluted renal tubule cells, activated macrophages, activated astrocytes, keratinocytes, placenta	HIV-protease inhibitors
		CYP39A1
		CYP46 / cholesterol 24-hydroxylase
		CYP51A1 / steroid 14a-demethylase			ketoconazole (Nizoral^®)
		NAT1
		NAT2 : 15 SNPs	isoniazid procainamide dapsone hydralazine caffeine
		dihydropyrimidine dehydrogenase (DPYD)	5-FU
		thiopurine S-methyltransferase (TPMT)	6-MP
		epoxide hydrolase 1			valproic acid
		TGM1 / K polypeptide epidermal type I, protein-glutamine-g-glutamyltransferase
		TGM2 / C polypeptide, protein-glutamine-g-glutamyltransferase			immunodominant gluten peptide in which Gln has been replaced with a 6-diazo-5-oxo-Nle residue
		TGM3 / E polypeptide, protein-glutamine-g-glutamyltransferase
		TGM3-like
		TGM4	prostate
		TGM5
		TGM6 / coagulation factor XIII
		TGM7 / transglutaminase Z
	aminopeptidases	aminopeptidase N / CD13			competitive inhibitors : ubenimex actinonin
		leucine aminopeptidase (LAP3)			bestatin CHR-2797 / tosedostat (source : Chroma Therapeutics Ltd; orally bioavailable) is a novel metalloenzyme inhibitor that is converted into a pharmacologically active acid product (CHR-79888) inside cells^ref
		placental leucine aminopeptidase
		adipocyte-derived leucine aminopeptidase / ERAP1
		methionine aminopeptidase-1 (MetAP-1)
		methionine aminopeptidase-2 (MetAP-2)			replacement of the C4 side chain by benzyloxime preserves the inhibitory activity against MetAP-2 enzyme fumagillin ovalicin bestatin-type A-357300 O-(chloracetyl-carbamoyl) fumagillol / TNP-470 /AGM-1470, an analogue of fumagillin toxic to proliferative endothelial cells : a water-soluble conjugate of biocompatible N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer, Gly-Phe-Leu-Gly linker and TNP-470 prevents it crossing the blood–brain barrier (BBB), and also leads to its selective accumulation in tumour vessels because of the enhanced permeability and retention (EPR) effect, thereby minimizing weight loss and neurotoxicity^ref. FK866/K22.175 (FK-866), developed as an anticancer agent, interferes with the NAD+ biosynthesis and a strong antiangiogenic potency^ref


ATP-binding cassette (ABC) proteins : the human's 49 known ABC genes are beat out by fly, worm and mouse (56, 56, and 51 respectively), and are dwarfed by the 129 known Arabidopsis thaliana genes.		ABCA1 (monomeric)	liver, intestine, placenta, adipose, and spleen
		ABCA2
		ABCA3
		ABCA4
		ABCA5
		ABCA6
		ABCA7
		ABCA8
		ABCA9
		ABCA10
		ABCA11
		ABCA12
		ABCA13
		ABCB1/ P-glycoprotein (P-GP) / MDR1 / GP170	lumenal surface of brain capillaries (blood-brain barrier (BBB)) neurons testes proximal renal tubular cells enterocytes pancreas bronchial mucosa hepatocytes placenta low expression on blood cells, gonads, and breast	amphipathic, lipid soluble : loperamide HIV protease inhibitors paclitaxel quinine sulfate and quinidine verapamil ketoconazole imatinib INNO-406		first-generation agents : cyclosporine-A quinine sulfate and quinidine verapamil second-generation agents : biricodar dictrate (Incel^®) valspodar / PSC 833 (Amdray^®) third-generation inhibitors : laniquidar / R101933 ONT-093 tariquidar / XR9576 zosuquidar trihydrochloride / LY335979
		ABCB2 / TAP1
		ABCB3 / TAP2
		ABCB4
		ABCB5
		ABCB6	highly expressed in human fetal liver^ref	iron porphyrin
		ABCB7		heme from mitochondria to cytosol
		ABCB8
		ABCB9
		ABCB10
		ABCB11 / bile salt efflux pump (BSEP)		bile salts across hepatocyte canalicular mebrane into bile
		ABCC1 / MDR-associated protein type 1 (MRP1)		oxidized glutatione cysteinyl leukotrienes activated aflatoxin B₁ glucuronides and sulfate conjugates of steroid hormones and bile salts
		ABCC2 / MDR-associated protein type 2 (MRP2)	brush border of proximal renal tubule hepatocytes apical membrane of enterocytes	amphipathic anions and conjugated metabolites vinblastine glucuronides sulfates glutathione adducts
		ABCC3 / MDR-associated protein 3 (MRP3)
		ABCC4 / MDR-associated protein 4 (MRP4)	brain tumor cells	topotecan
		ABCC5 / MDR-associated protein 5 (MRP5)
		ABCC6 / MDR-associated protein 6 (MRP6)
		ABCC7 / CFTR is unique among ABC proteins in that its transmembrane domains comprise an ion channel. Opening and closing of the pore have been linked to ATP binding and hydrolysis at CFTR's 2 nucleotide-binding domains, NBD1 and NBD2)^ref		Cl^- HCO₃^- + Cl^-		2-thioxo-4-thiazolidinones : CFTR_inh-172 (K_i = 300 nM) glyburide / glibenclamide (Micronase^®, Diabeta^®, Euglucan^®, Glynase^®; Glucovance^® in combination with metformin ) niflumic acid (NFA) (Niflam^®) diphenylamine-2-carboxylate
		ABCC8 / MDR-associated protein 8 (MRP8) / sulfonylurea receptor 1 (SUR1) (associated to KCNJ11 )^ref	b cells of pancreatic Langerhans' islets^ref		a endosulfine b endosulfine sulfonylureas : first-generation analogs tolbutamide (Orinase^®) chlorpropamide (Diabinese^®; Chlorformin^® in combination with phenformin ) tolazamide (Tolinase^®) acetohexamide (Dymelor^®) second-generation analogs glyburide / glibenclamide (Micronase^®, Diabeta^®, Euglucan^®, Glynase^®; Glucovance^® in combination with metformin ) glipizide (Glucotrol^®) gliclazide (Diamicron^®, ...) immediate release (IR) modified reease (MR) glimepiride (Amaryl^®) meglitinide analogues : repaglinide (Prandin^®) nateglinide (Starlix^®) mitiglinide / KAD-1229
		ABCC9 / sulfonylurea receptor 2 (SUR2)^ref	cardiac, skeletal, and vascular and non-vascular smooth muscle		sulfonylureas: first-generation analogs tolbutamide (Orinase^®) chlorpropamide (Diabinese^®) tolazamide (Tolinase^®) acetohexamide (Dymelor^®) second-generation analogs glyburide / glibenclamide (Micronase^®, Diabeta^®, Glynase^®; Glucovance^® in combination with metformin ) glipizide (Glucotrol^®) gliclazide (Diamicron^®, ...) immediate release (IR) modified reease (MR) glimepiride (Amaryl^®) meglitinide analogues repaglinide (Prandin^®) nateglinide (Starlix^®) mitiglinide / KAD-1229
		ABCC10 / MDR-associated protein 7 (MRP7)
		ABCC11 / MDR-associated protein 8 (MRP8)
		ABCC12 / MDR-associated protein 9 (MRP9)
		ABCC13
		ABCD1
		ABCD2
		ABCD3
		ABCD4
		ABCE1
		ABCF1
		ABCF2
		ABCF3
		ABCG1 (dimeric)	macrophages
		ABCG2 / BRCP	cancer cells	mitoxantrone (sequestered into extracellular vesicles^ref)		Ko143 fumitremorgin C imatinib
		ABCG3
		ABCG4 (dimeric)	macrophages
		ABCG5 / sterolin-1 (dimeric)	liver and small intestine (apical sterol export pumps that promote active efflux of cholesterol and plant sterols from enterocytes back into the intestinal lumen for excretion)	sterolins / phytosterols
		ABCG8 / sterolin-2 (dimeric)		sterolins / phytosterols


		ATP1A1 : ATPase, Na+/K+ transporting, alpha 1 polypeptide
		ATP1A2 ATPase, Na+/K+ transporting, alpha 2 (+) polypeptide
		ATP1A3 ATPase, Na+/K+ transporting, alpha 3 polypeptide
		ATP1A4 ATPase, Na+/K+ transporting, alpha 4 polypeptide
		ATP1B1 ATPase, Na+/K+ transporting, beta 1 polypeptide
		ATP1B2 ATPase, Na+/K+ transporting, beta 2 polypeptide
		ATP1B3 ATPase, Na+/K+ transporting, beta 3 polypeptide
		ATP1B4 ATPase, (Na+)/K+ transporting, beta 4 polypeptide
	sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA)	ATP2A1 / SERCA1		cardiac muscle, fast twitch 1		thapsigargin L12ADT
		ATP2A2 / SERCA2 (2 isoforms : SERCA2a and SERCA2b)		cardiac muscle, slow twitch 2		thapsigargin L12ADT
		ATP2A3 / SERCA3		ubiquitous		thapsigargin L12ADT
		ATP3 ATPase, Mg++ transporting
		ATP4A ATPase, H+/K+ exchanging, alpha polypeptide
		ATP4B ATPase, H+/K+ exchanging, beta polypeptide
		ATP5A1 ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit, isoform 1, cardiac muscle
		ATP5A2 ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit, isoform 2, non-cardiac muscle
		ATP5B ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide
		ATP5C1 ATP synthase, H+ transporting, mitochondrial F1 complex, gamma polypeptide 1
		ATP5C2 ATP synthase, H+ transporting, mitochondrial F1 complex, gamma polypeptide 2
		ATP5D ATP synthase, H+ transporting, mitochondrial F1 complex, delta subunit
		ATP5E ATP synthase, H+ transporting, mitochondrial F1 complex, epsilon subunit
		ATP5F1 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit b, isoform 1
		ATP5G1 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit c (subunit 9), isoform 1
		ATP5G2 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit c (subunit 9), isoform 2
		ATP5G3 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit c (subunit 9) isoform 3
		ATP5H ATP synthase, H+ transporting, mitochondrial F0 complex, subunit d
		ATP5I ATP synthase, H+ transporting, mitochondrial F0 complex, subunit e
		ATP5J ATP synthase, H+ transporting, mitochondrial F0 complex, subunit F6
		ATP5L ATP synthase, H+ transporting, mitochondrial F0 complex, subunit g
		MTATP6 ATP synthase 6
		ATP7A ATPase, Cu⁺ transporting, a polypeptide (Menkes syndrome)
		ATP7B ATPase, Cu⁺ transporting, b polypeptide (Wilson disease)
		MTATP8 ATP synthase 8
		ATP9A ATPase, Class II, type 9A
		ATP9B ATPase, Class II, type 9B
		ATP10A ATPase, Class V, type 10A
		ATP10B ATPase, Class V, type 10B
		ATP10D ATPase, Class V, type 10D
		ATPAF1 ATP synthase mitochondrial F1 complex assembly factor 1
		ATPAF2 ATP synthase mitochondrial F1 complex assembly factor 2



	farnesyl diphosphate synthase (farnesyl pyrophosphate synthetase, dimethylallyltranstransferase, geranyltranstransferase)			bisphosphonates are pyrophosphate analogs : first-generation, nonnitrogen-containing bisphosphonates have antiresorptive activity at dose levels from 0.1 to 10 mg P/kg. Some first generation analogues are now used to treat metabolic bone disease but, when given orally, their efficacy in aggressive resorptive disease may be limited because of low potency clodronate (Bonefos^®) etidronate sodium / ethylenehydroxydiphosphonate (Didrocal^®, Didronel^®) aminobisphosphonates / nitrogen-containing bisphosphonates (N-BPs) second generation amino-bisphosphonates characterized by an amino terminal group and a higher antiresorptive potency (in growing rats ranges from 0.01 to 1 mg P/kg.) alendronate (Fosamax^®; Merck and Company, Inc.; West Point, PA) p.o. pamidronate / aminohydroxypropane diphosphonate (Aredia^®; Novartis Pharmaceuticals Corp.; East Hanover, NJ) i.v. third generation bisphosphonates are characterized by a cyclic chain, was synthesized. It includes series of pyridinyl ethane bisphosphonates, pyridinyl aminomethane bisphosphonates, indan bisphosphonates, cyclopentane bisphosphonates, piperidyl ethane bisphosphonates, pyridinyl and piperidyl hydroxyethane bisphosphonates, piperidinylidene aminomethane bisphosphonates, and pyridinyl oxa- and thiomethane bisphosphonates. Several of these show antiresorptive activity in growing rats as low as 0.001 mg P/kg ibandronate (Bondronat^®, Bonvival^®; Hoffmann-La Roche Inc.; Nutley, NJ) i.v. risedronate (Actonel^®; Actonel with Calcium^® in combination with calcium carbonate; Proctor and Gamble Pharmaceuticals, Inc.; Cincinnati, OH) p.o. zoledronate (Zometa^®; Novartis Pharmaceuticals Corp.) i.v. medronate / methylene diphosphonate minodronate (YM529) neridronate olpadronate oxidronate / hydroxymethylene diphosphonate tiludronate (Skelid^®)
	farnesyl-diphosphate farnesyltransferase 1 (FDFT1)	farnesyl pyrophosphate		farnesyl transferase inhibitors (FTI) : synthetic FTIs have been designed based on the structures of 2 substrates that are involved in the reaction, FPP and Ras CAAX tetrapeptide. Ras-competitive inhibitors that have been synthesized, both CAAX-related and CAAX-unrelated, display nanomolar inhibitory potency toward FTase but retain selectivity against GGTase-I p.o. lonafarnib / SCH66336 (Sarasar^®) tipifarnib / R115777 (Zarnestra^®) i.v. : BMS-214662 J-104,871^ref

	poly(ADP-ribose) polymerase (PARP)			PJ34 (phenanthridinone-based) INO-1001 3-aminobenzamide (ABA) 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2h)-isoquinolinone olaparib (AZD2281)
	thiamine pyrophosphokinase		thiamine => TPP / TDP	neopyrithiamine / pyrithiamine oxythiamine
	pyridoxal kinase		pyridoxal => pyridoxal phosphate	isonicotinic acid hydrazone
calmodulins	calmodulin 1 calmodulin 2 calmodulin 3 calmodulin-like 1 calmodulin-like 3			zaldaride
	glyceraldehyde-3-phosphate dehydrogenase (GAPDH)			koningic acid (KA)
	telomerase reverse transcriptase (TERT)			catalytic inhibitors antisense phosphorothioate (AS-ONS) for telomerase template GRN163 (a 13-mer N3'-->P5' thio-phosphoramidate (NPS) oligonucleotide) folding of the DNA substrate inhibitors of the HSP90 chaperone function : geldanamycin (GA) 17-allylamino,17-demethoxygeldanamycin (17-AAG) AZT / zidovudine lamivudine 3-(3,5-dichlorophenoxy)-nitrostyrene (DPNS) 2,3,7-trichloro-5-nitroquinoxaline (TNQX) dictyodendrins A-E (1-5) 2,3-dibromosuccinato [2-(methylaminomethyl)pyridine]platinum (II) (compound E) epigallocatechin gallate (EGCG) and synthetic derivatives : SR13193 SR13196 gossypol MST-312 MST-295 MST-1991 arabinofuranosylguanine 5'-triphosphate (araGTP) 3'-azido-2',3'-dideoxyguanosine 5'-triphosphate (AZdGTP) 2',3'-dideoxy-2'-fluoroarabino-furanosylguanine 5'-triphosphate (FaraGTP) quadruplex telomeric G-rich ssDNA telomestatin (SOT-095)


matrix metalloproteinases (MMP) : multidomain zinc endopeptidases with a metzincin-like catalytic domain	MMP1 / interstitial collagenase		batimastat / BB-94 (hydroxamate peptidomimetic ) ilomastat / galardin / GM 6001 marimastat / BB 2516 / TA 2516 (orally bioavailable analogue ) SC 44463 o-phenanthroline collagen peptidomimetics nonpeptidomimetic inhibitors of the MMP active site tetracycline derivatives competing for Zn : doxycycline tetracycline nonantibiotic chemically modified tetracyclines Col-3 bisphosphonates
	MMP2 / gelatinase A / 72 kDa type IV collagenase
	MMP3 / stromelysin 1 / progelatinase
	MMP7 / uterine matrilysin
	MMP8 / neutrophil collagenase
	MMP9 / gelatinase B / 92 kDa type IV collagenase
	MMP10 / stromelysin 2
	MMP11 / stromelysin 3
	MMP12 / macrophage elastase
	MMP13 / collagenase 3
	MMP14 / MT1-MMP / membrane inserted (an activator of MMP-2)
	MMP15 / membrane inserted
	MMP16 / membrane inserted
	MMP17 / membrane inserted
	MMP18 / MMP19
	MMP20 / enamelysin
	MMP21
	MMP23A
	MMP23B / MMP22
	MMP24 / membrane inserted
	MMP25
	MMP26
	MMP27
	MMP28
calpain			MDL 28170
cholesteryl ester transfer protein, plasma (CETP)		hepatocytes	JTT-705 torcetrapib / CP-529414 anacetrapib / MK-0859
lipase, gastric			orlistat / tetrahydrolipstatin (THL) (Xenical^®) ATL-962
lipase, pancreatic			orlistat / tetrahydrolipstatin (THL) (Xenical^®) ATL-962
HMG-CoA reductase	HMG-CoA	hepatocytes	-statins / HMGRIs : atorvastatin (Lipitor^®, Totalip^®) cerivastatin (Baycol^®, Stativa^®, Cervasta^®) fluvastatin (Lescol^®) lovastatin / mevilonin (prodrug) (Mevacor^®) mevastatin / compactin ^ref pitavastatin / NK-104 (Livalo^®) pravastatin (Pravachol^®) rosuvastatin / ZD4522 (Crestor^®, Simestat^®) simvastatin (prodrug) (Zocor^®; Vytorin^® or Inegy^® in combination with ezetimibe )
microsomal triglyceride transfer protein (MTP)			lomitapide / AEGR-773 / BMS-201038 (Juxtapid^®)
acylCoA:cholesterol acyltransferase 1 (ACAT-1)	cholesterol, acylCoA	macrophage	avasimibe / CI-1011
acylCoA:cholesterol acyltransferase 2 (ACAT-2)	cholesterol	enterocytes and hepatocytes
Pim kinases	Pim-1		SGI-1776
	Pim-2
	Pim-3
lipoprotein lipase (LPL)		adipocytes, skeletal muscle cells, and macrophages (including foamy cells in atherosclerotic lesions, where it can bind and retain LDLs in subendothelial space)
hepatic triglyceride lipase (HTGL)		hepatocytes
phospholipid transfer protein (PLTP)		liver and lungs
lecithin:cholesterol acyl transferase (LCAT)		hepatocytes
squalene synthase / farnesyl-diphosphate farnesyl transferase 1	farnesyl pyrophosphate		squalestatin 1^ref zaragosic acids A, B, and C (fungal metabolites)^ref 1,1-bisphosphonate esters : SR-45023A (Apomine^TM) ?^ref SR-12813^ref ER-27856 5-{N-[2-butenyl-3-(2-methoxyphenyl)]-N-methylamino}-1,1-penthylidenebis(phosphonic acid) trisodium salt^ref RPR 107393 {3-hydroxy-3-[4-(quinolin-6-yl)phenyl]-1-azabicyclo[2-2-2]octane dihydrochloride} and its R and S enantiomers (p.o.; also inducer of HMG-CoA reductase, resulting in the accumulation of metabolites of FPP. After the administration of radiolabeled mevalonate, hepatic levels of labeled dicarboxylic acids in RPR 107393-treated rats were shown in the present study, raising the possibility of toxicity with this treatment. It is known, however, that dicarboxylic acids derived from geraniol are readily excreted in urine, so rapid urinary excretion as the dicarboxylic acids may be the fate of the accumulated mevalonate after RPR 107393 treatment^ref) some bisphosphonates^{ref1, ref2}
GTP cyclohydrolase I (GTPCH)			2,4-diamino-6-hydroxypyrimidine
N-acetyl-L-aspartyl-L-glutamate (NAAG) peptidase / glutamate carboxypeptidase II (GCPII)	N-acetyl-aspartyl-glutamate (NAAG)		2-(phosphonomethyl) pentanedioic acid (2-PMPA) ZJ-43
HIF-1a prolyl 4-hydroxylase (HPH)
dipeptidyl peptidase 4 (DPP-4)	GLP-1 CXCL12		sitagliptin phosphate / MK-0431 (Januvia^®; JanuMet^® in combination with metformin ) vildagliptin / LAF-237 (Galvus^®) saxagliptin / BMS-477118 (Onglyza^®)
Syk			R788 (fostamatinib disodium), an oral prodrug that is rapidly converted to a potent and relatively selective inhibitor of Syk (R406)^ref
ALK			crizotinib / PF-02341066 (Pfizer)
Aurora kinases^ref	Aurora A kinase		MLN8504 (Aurora-A IC₅₀ = 0.034 µmol/L; Aurora-B IC₅₀ = 5.7 µmol/L)
	Aurora B kinase		indolinone quinazoline derivatives : hesperadin (Boeheringer Ingelheim) 4,6-diaminopyrimidine : ZM447439 AZD1152-HQPA (Aurora B-selective) tetrahydropyrrolo[3,4-c]pyrazole derivative : PHA-739358 MK-0457 / VX680 (source: Vertex => Merck) AT9283 (source : Astex therapeutics) AS703569 ZM447439 (source : AstraZeneca) (both Aurora-A and Aurora-B with an IC50 of ~100 nmol/L) Compound 677 (source : AstraZeneca) (Aurora B-selective)
	Aurora C kinase

GTP-binding proteins, or GTPases^ref, are proteins that cycle back and forth between 2 conformations that determine their activity: in the first conformation, they are bound by a GTP cofactor that activates them biochemically; whereas, in the second conformation, they are GDP-bound and inactive. GTPases have hydrolysis activity that catalyses the conversion of the GTP moiety to GDP or GMP (GDP in the case of the p47 GTPases). The level of hydrolysis activity varies for particular GTPases, and it canbe modulated by other cellular factors, such as GTPase-activating factors, such as GTPase-activting proteins (GAPs). Once the protein is in the GDP-bound/inactive state, a cellular guanine exchange factor (GEF) catalyses the replacement of GDP with GTP, which reactivates the protein. So, the activity of GTPases is regulted by functions that are inherent to the protein as well as by accessory proteins. The fraction of the GTPase that is in the active state varies widely according to the particular GTPase, and according to the cellular environment. For example, the small GTPase RAS is about 7% GTP-bound in queiescent fibroblasts, but becomes more active and 22% is GTP-bound in fibroblasts that have been transformed by the v-src and v-abl viruses^ref. By contrast, most of the p47 GTPases in cells seem to be in a GTP-bound state, and are therefore active. At the primary sequence level, GTPases have 3 conserved amino-acid motifs- Gly-Xaa-Xaa-Xaa-Xaa-Gly-Lys(Ser/Thr), Asp-Xaa-Xaa-Gly and Asn-Lys-Xaa-Asp - that bind the guanine nucleotide and a Mg²⁺ cofactor^ref. In addition, some GTPases are membrane bound, with a covalently attached lipid chain such as myristoyl or prenyl group that medites association with the membrane^ref. Once in the GTP-bound state, GTPases effect their functions, which range from activation of cell surface receptors to modulation of membrane-fusion events. Although the precise cellular function of the p47 GTPases is unknown, GTP binding triggers the formation of oligomeric complexes.

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