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
    ceramide kinase (CERK)ref
    mammalian target of rapamycin (mTOR)
  • 6-dimethylaminopurine 
  • sirolimus / rapamycin (Rapamune®) complexed to FKBP1A / FKBP12 
  • everolimus / SDZ RAD / 40-O-(2-hydroxyethyl)-rapamycin (Certican®)
  • temsirolimus / CII-779
  • deforolimus 
  • CCI-779
  • AP23573
    		•
    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 / 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
    protein serine / threonine kinases Raf1 BAY 43-9006 / sorafenib (Nexavar®) (also inhibits RTKs FLT-3, VEGFR2 and c-KIT)
    GSK-3b 6-dimethylaminopurine 
    6-bromoindirubin-3'-oxime (BIO) 
    Li+
    CDK1 & CDK2 6-dimethylaminopurine 
    flavopiridol 
    UCN-01 / 7-hydroxystaurosporine
    seliciclib (CYC202; R-roscovitine) 
    indirubin
    CDK9 6-dimethylaminopurine 
    flavopiridol
    p70S6K 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
    		 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 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)
    • DAG-dependent and Ca2+-independent or novel (nPKC)
    • DAG- and Ca2+-independent, PI-3,4,5-P3-dependent or atypical (aPKC)
    • 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) 
    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)  SU5146
    CP-690,550
    Src family (in some RCTKs the SH4 domain is also palmitoylated)  PP2, middle t antigen from SV40
    / 
    /
    CGP57148, 
    imatinib mesylate / STI 571 (Gleevec / Glivec©) 
    / 
    / 
    / 
    / 
    / 
    /
    protein threonine / tyrosine kinases MAPKK / MEK UO126 
    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 : 
    • subclass IB (stimulated by Gbg subunits)
      • adapter or regulatory subunit : 
  • class II (+ C2 domain)
  • class III :
    • VPS34

      • adapter or regulatory subunit : 
    		middle t antigen from SV40 LY294002 
    radicicol 
    wortmannin
    diacylglycerol kinase (DAGK)  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 glycogen phosphorylase (inhibited) 
    p105Rb (inhibited) 
    p80cdc25 (inhibited) 
    eIF2a (activated) 
    glycogen synthase (activated) 
    IkBa (activated) 
    X (activated or inhibited)    		 tautomycin
    tautomycetin (TMC)
    iodoacetic acid 
    sodium orthovanadate 
    sodium pervanadate (VO43-) 
    okadaic acid (weak inhibition) 
    microcystin-LR
    PP2A / PPIIA tautomycin
    iodoacetic acid 
    sodium orthovanadate 
    sodium pervanadate (VO43-) 
    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 (VO43-) 
    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 (VO43-)
    PP5 / PPV iodoacetic acid 
    sodium orthovanadate 
    sodium pervanadate (VO43-)
    PP6 / PPVI iodoacetic acid 
    sodium orthovanadate 
    sodium pervanadate (VO43-)
    PP7 / PPVII iodoacetic acid 
    sodium orthovanadate 
    sodium pervanadate (VO43-)
    protein tyrosine phosphatase (PTP) SHP-1 / PTP-1C / hematopoetic cell phosphatase (HCP) / SHPTP1 / SHP / PTPN6  sodium stilbogluconate (SSG) 
    iodoacetic acid 
    sodium orthovanadate 
    sodium pervanadate (VO43-)
    SHP-2 / PTP-2C / Syp / PTP-1D / SH-PTP2 / PTPN11 iodoacetic acid 
    sodium orthovanadate 
    sodium pervanadate (VO43-)
    hPTP1E / PTPBAS / FAP1 
    PTP2E (Rattus norvegicus) 
    R-PTP y    		 iodoacetic acid 
    sodium orthovanadate 
    sodium pervanadate (VO43-)
    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    		 VO43-
    protein threonine / tyrosine phosphatase Cdc25 VO43-
    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 (+ Gas, PKC, Ca2+CaM ;- Gai, Ga0, Gaz, b5g2, b1g2, Ca2+)
    AC2 (+ : PKC; - : b5g2, b1g2) 
    AC3 (+ : PKC, Ca2+CaM ; - : Gai, Ca2+) 
    AC4 (+ : ; - : PKC) 
    AC5 (+ : PKC; - : PKA, Ga0, Gai, Gaz, Ca2+), 
    AC6 (+ : ; - : PKA, Ga0, Gai, Ca2+) 
    AC7 (+ : PKC, Ca2+CaM ; - : ) 
    AC8 (+ : ; - : ) 
    AC9 (+ : ; - : Ca2+)    		 ATP => cAMP + PPi 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 
    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]quinoxalinesref
    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) 
    thymidine kinase 
    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) (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  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 topoisomerase II / DNA girase (p170a or p180b) 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
    histone deacetylase (HD / HDAC) histone deacetylase 1 (HDAC1)
    Rpd1 (it binds Sin3 corepressor and Ume6)     		 HDAC inhibitors (HDIs) : 
    • vorinostat / suberoylanilide hydroxamic acid (SAHA) / NVP-LAQ824 
    • short chain fatty acid sodium butyrate (NaB)
    • trichostatin A (TSA)
    • romidepsin / FK228 / bicyclic depsipeptide FR 901228
    • m-carboxycinnamic acid bis-hydroxamide (CBHA)
    • MS275 / N-(2-aminophenyl)-4-[N-(pyridin-3-yl-methoxycarbonyl)amino- methyl]benzamide 
    • valproic acid (VPA) (PEAC minitablets©; source: TopoTarget A/S)
    • LBH589 inhibits HDAC6 / tubulin deacetylase (TDAC)
    • PXD101
    SIRT1 / Sir2a p53 resveratrol
    histone acetyltransferase (HAT) p300 / CBP
    TAFII250
    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) : 
    phospholipases phospholipase A1 (PS-specific) removes FA in sn-1 from 1,2- diacylglycero phospholipids
    phospholipase A2 mellitin
    mepacrine 
    4-Br- phenacylbromure    		 Bi 
    4-bromophenacylbromide
    phospholipase B
    phospholipase Cb (activated by GqPCRs; found only in Metazoa) 
    phospholipase Cg (activated by RTKs; found only in Metazoa) 
    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  Rap family 
    Rab family 
    Rho family  Rac family 
    Ran family
    Ras family      		TAT-C3
    GNRP / GEF / GDS Dbl 
    TIAM1
    GRF1 (Ca2+-CaM-dependent) 
    GRF2 / Epac / C3G
    EF-Ts
    eIF2B  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 / p120GAP
    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-2ref    		 5,8,11,14-eicosatetraynoic acid 
    nonsteroidal antiinflammatory drugs (NSAIDs)
    • alkanones
      • nabumetone (Relafen®)
    • tenidap (Enablex®) 
    • azapropazone / apazone (Rheumox®)
    • acetanilide => p-aminophenol => phenacetin / acetophenetidin => acetaminophen / paracetamol / N-acetyl-p-aminophenol (Acetanol®, Liquiprin®, Panadol®, Tachipirina®, Tylenol®; Perfalgan® i.v.; Talcen® in combination with pentazocine; Percocet® and Tylox® in combination with oxycodone; Co-efferalgan® in combination with codeine; Mersyndol®

      • in combination with codeineand doxylamine; Algosil®, Antinevralgico Knapp®, Antireumina®, Drin®, Neocibelgina®, Neonevral®, Neonisidina®, Verdal® in combination with acetylsalicylic acid and caffeine) (on COX-3 only: antipyretic but not antiinflammatory as WBC-derived peroxides inhibit it) 
    • 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-1ref    		 COX-1 antagonists
    acetanilide => p-aminophenol => phenacetin / acetophenetidin => acetaminophen / paracetamol / N-acetyl-p-aminophenol  (Tachipirina®, Tylenol®; Talcen® in combination with pentazocine; Percocet® and Tylox® in combination with oxycodone; Co-efferalgan® in combination with codeine) (on COX-2b only) 
    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 :
      • 1st generation coxibs :
        • diaryl-substituted pyrazoles 
          • celecoxib (Celebrex®)
          • OSU03012
        • diaryl-substituted furanones 
          • rofecoxib (Arofexx®, Vioxx®)
      • 2nd 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 / PGF2a 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
    LTA4 hydrolase (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
    LTB4 12-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)
    tryptophan 3-monooxygenase 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-Proref
    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