{
  "chemblVersion": "ChEMBL_37",
  "chemblReleaseDate": "2026-05-01",
  "rdkitVersion": "2025.03.5",
  "population": 2104,
  "populationWithFirstApproval": 1805,
  "candidates": 228,
  "decisions": {
    "covalent": 173,
    "not_covalent": 55
  },
  "broad": 173,
  "broadPct": 8.2,
  "strict": 36,
  "strictPct": 1.7,
  "broadByTargetKind": {
    "Protein serine": 92,
    "Protein cysteine": 40,
    "DNA": 24,
    "Prosthetic group (FAD) of target": 9,
    "Protein threonine": 3,
    "Protein residue (not assigned)": 2,
    "RNA (tRNA terminus)": 1,
    "Protein lysine": 1,
    "Protein N-terminus": 1
  },
  "broadByWarheadClass": {
    "Beta-lactam": 72,
    "Acrylamide": 14,
    "Nitrogen mustard": 9,
    "Aryl carbamate": 6,
    "Sulfinyl benzimidazole (prodrug)": 6,
    "Hydrazine": 6,
    "Fluoropyrimidine": 5,
    "Nitrile": 4,
    "Boronic acid": 4,
    "Diazabicyclooctane": 3,
    "Nitrosourea": 3,
    "Thienopyridine (prodrug)": 3,
    "Methylating triazene or hydrazine": 3,
    "Fumarate Michael acceptor": 3,
    "Organophosphate": 3,
    "Enzyme-activated inactivator": 3,
    "Propargylamine": 3,
    "Butynamide": 2,
    "Azacytosine nucleoside": 2,
    "Ketoamide": 2,
    "Alkyl sulfonate": 2,
    "Carbinolamine alkylator": 2,
    "Psoralen (photoactivated)": 2,
    "Aziridine": 2,
    "Aryl ester (acyl donor)": 1,
    "Epoxyketone": 1,
    "Disulfide": 1,
    "Epoxide": 1,
    "Cyanoenone": 1,
    "Beta-lactone": 1,
    "Haloalkylamine (aziridinium)": 1,
    "Bromoalkyl amide": 1,
    "Aldehyde": 1
  },
  "strictByWarheadClass": {
    "Acrylamide": 14,
    "Nitrile": 4,
    "Diazabicyclooctane": 3,
    "Boronic acid": 3,
    "Beta-lactam": 3,
    "Butynamide": 2,
    "Ketoamide": 2,
    "Enzyme-activated inactivator": 2,
    "Epoxyketone": 1,
    "Cyanoenone": 1,
    "Aldehyde": 1
  },
  "broadByTargetClass": {
    "Bacterial cell-wall enzymes": 77,
    "Other enzymes": 32,
    "DNA": 24,
    "Protein kinases": 13,
    "Proteases": 9,
    "Small GTPases and other proteins": 8,
    "Transporters and pumps": 6,
    "GPCRs": 4
  },
  "strictByTargetClass": {
    "Protein kinases": 13,
    "Proteases": 9,
    "Bacterial cell-wall enzymes": 7,
    "Small GTPases and other proteins": 5,
    "Other enzymes": 2
  },
  "broadByReversibility": {
    "Irreversible": 151,
    "Reversible": 16,
    "Slowly reversible": 6
  },
  "strictByReversibility": {
    "Irreversible": 21,
    "Reversible": 15
  },
  "broadByDecade": {
    "Before 1950": 2,
    "1950s": 13,
    "1960s": 11,
    "1970s": 20,
    "1980s": 36,
    "1990s": 19,
    "2000s": 17,
    "2010s": 24,
    "2020s": 17,
    "No ChEMBL first-approval year": 14
  },
  "strictByDecade": {
    "1980s": 1,
    "1990s": 2,
    "2000s": 5,
    "2010s": 16,
    "2020s": 11,
    "No ChEMBL first-approval year": 1
  },
  "allApprovedByDecade": {
    "Before 1950": 43,
    "1950s": 140,
    "1960s": 143,
    "1970s": 172,
    "1980s": 349,
    "1990s": 305,
    "2000s": 233,
    "2010s": 268,
    "2020s": 152
  },
  "broadByBondTarget": {
    "Protein": 148,
    "DNA": 24,
    "RNA": 1
  },
  "broadByWarheadFamily": {
    "Beta-lactams": 72,
    "DNA alkylators": 24,
    "Michael acceptors": 20,
    "Disulfide-forming drugs": 10,
    "Other": 9,
    "Cholinesterase inhibitors": 9,
    "MAO inhibitors": 9,
    "Boronic acids and DBOs": 7,
    "Nucleoside analogs": 7,
    "Nitriles and ketoamides": 6
  },
  "otherWarheadClasses": [
    "Aldehyde",
    "Aryl ester (acyl donor)",
    "Beta-lactone",
    "Enzyme-activated inactivator",
    "Epoxide",
    "Epoxyketone",
    "Haloalkylamine (aziridinium)"
  ],
  "kinaseCumulativeByYear": [
    {
      "year": 2001,
      "allKinaseInhibitors": 2,
      "covalent": 0
    },
    {
      "year": 2002,
      "allKinaseInhibitors": 2,
      "covalent": 0
    },
    {
      "year": 2003,
      "allKinaseInhibitors": 3,
      "covalent": 0
    },
    {
      "year": 2004,
      "allKinaseInhibitors": 4,
      "covalent": 0
    },
    {
      "year": 2005,
      "allKinaseInhibitors": 5,
      "covalent": 0
    },
    {
      "year": 2006,
      "allKinaseInhibitors": 7,
      "covalent": 0
    },
    {
      "year": 2007,
      "allKinaseInhibitors": 10,
      "covalent": 0
    },
    {
      "year": 2008,
      "allKinaseInhibitors": 10,
      "covalent": 0
    },
    {
      "year": 2009,
      "allKinaseInhibitors": 12,
      "covalent": 0
    },
    {
      "year": 2010,
      "allKinaseInhibitors": 12,
      "covalent": 0
    },
    {
      "year": 2011,
      "allKinaseInhibitors": 16,
      "covalent": 0
    },
    {
      "year": 2012,
      "allKinaseInhibitors": 21,
      "covalent": 0
    },
    {
      "year": 2013,
      "allKinaseInhibitors": 25,
      "covalent": 2
    },
    {
      "year": 2014,
      "allKinaseInhibitors": 28,
      "covalent": 2
    },
    {
      "year": 2015,
      "allKinaseInhibitors": 33,
      "covalent": 3
    },
    {
      "year": 2016,
      "allKinaseInhibitors": 34,
      "covalent": 4
    },
    {
      "year": 2017,
      "allKinaseInhibitors": 42,
      "covalent": 6
    },
    {
      "year": 2018,
      "allKinaseInhibitors": 49,
      "covalent": 7
    },
    {
      "year": 2019,
      "allKinaseInhibitors": 55,
      "covalent": 8
    },
    {
      "year": 2020,
      "allKinaseInhibitors": 64,
      "covalent": 9
    },
    {
      "year": 2021,
      "allKinaseInhibitors": 69,
      "covalent": 10
    },
    {
      "year": 2022,
      "allKinaseInhibitors": 71,
      "covalent": 11
    },
    {
      "year": 2023,
      "allKinaseInhibitors": 77,
      "covalent": 11
    },
    {
      "year": 2024,
      "allKinaseInhibitors": 78,
      "covalent": 12
    }
  ],
  "broadByResidue": {
    "Protein serine": 92,
    "Protein cysteine": 40,
    "Protein threonine": 3,
    "Protein residue (not assigned)": 2,
    "Protein lysine": 1,
    "Protein N-terminus": 1
  },
  "strictByResidue": {
    "Protein cysteine": 19,
    "Protein serine": 12,
    "Protein threonine": 3,
    "Protein lysine": 1,
    "Protein N-terminus": 1
  },
  "broadByEvidence": {
    "A": 153,
    "B": 20
  },
  "broadWithoutFirstApprovalYear": [
    "Anagliptin",
    "Cefamandole",
    "Cefpirome",
    "Cefpodoxime",
    "Cephaloridine",
    "Chlornaphazine",
    "Distigmine",
    "Iproniazid",
    "Mebanazine",
    "Nialamide",
    "Phenoxypropazine",
    "Physostigmine",
    "Pivampicillin",
    "Tegafur"
  ],
  "strictList": [
    [
      0,
      "Anagliptin"
    ],
    [
      1986,
      "Sulbactam"
    ],
    [
      1990,
      "Eflornithine"
    ],
    [
      1993,
      "Tazobactam"
    ],
    [
      2003,
      "Bortezomib"
    ],
    [
      2007,
      "Vildagliptin"
    ],
    [
      2009,
      "Carfilzomib"
    ],
    [
      2009,
      "Saxagliptin anhydrous"
    ],
    [
      2009,
      "Vigabatrin"
    ],
    [
      2011,
      "Boceprevir"
    ],
    [
      2011,
      "Telaprevir"
    ],
    [
      2013,
      "Afatinib"
    ],
    [
      2013,
      "Ibrutinib"
    ],
    [
      2015,
      "Avibactam"
    ],
    [
      2015,
      "Ixazomib citrate"
    ],
    [
      2015,
      "Osimertinib"
    ],
    [
      2016,
      "Olmutinib"
    ],
    [
      2017,
      "Acalabrutinib"
    ],
    [
      2017,
      "Neratinib"
    ],
    [
      2017,
      "Vaborbactam"
    ],
    [
      2018,
      "Dacomitinib anhydrous"
    ],
    [
      2019,
      "Relebactam anhydrous"
    ],
    [
      2019,
      "Selinexor"
    ],
    [
      2019,
      "Voxelotor"
    ],
    [
      2019,
      "Zanubrutinib"
    ],
    [
      2020,
      "Tirabrutinib"
    ],
    [
      2021,
      "Mobocertinib"
    ],
    [
      2021,
      "Sotorasib"
    ],
    [
      2022,
      "Adagrasib"
    ],
    [
      2022,
      "Futibatinib"
    ],
    [
      2023,
      "Durlobactam"
    ],
    [
      2023,
      "Nirmatrelvir"
    ],
    [
      2023,
      "Omaveloxolone"
    ],
    [
      2023,
      "Ritlecitinib"
    ],
    [
      2024,
      "Enmetazobactam"
    ],
    [
      2024,
      "Lazertinib"
    ]
  ],
  "broadWithoutBetaLactams": 101,
  "betaLactamsAll": 72,
  "strictWithoutPenicillanicSulfones": 33,
  "kinaseInhibitorsAll": 78,
  "kinaseInhibitorsCovalent": 13,
  "kinaseCovalentByYear": [
    [
      2013,
      "Afatinib"
    ],
    [
      2013,
      "Ibrutinib"
    ],
    [
      2015,
      "Osimertinib"
    ],
    [
      2016,
      "Olmutinib"
    ],
    [
      2017,
      "Acalabrutinib"
    ],
    [
      2017,
      "Neratinib"
    ],
    [
      2018,
      "Dacomitinib anhydrous"
    ],
    [
      2019,
      "Zanubrutinib"
    ],
    [
      2020,
      "Tirabrutinib"
    ],
    [
      2021,
      "Mobocertinib"
    ],
    [
      2022,
      "Futibatinib"
    ],
    [
      2023,
      "Ritlecitinib"
    ],
    [
      2024,
      "Lazertinib"
    ]
  ],
  "notCounted": [
    [
      "Acetylcysteine",
      "Thiol antioxidant; no covalent target"
    ],
    [
      "Allopurinol",
      "Oxypurinol coordinates the reduced molybdenum centre; no covalent bond to the protein"
    ],
    [
      "Alogliptin",
      "Benzonitrile; non-covalent DPP-4 inhibitor"
    ],
    [
      "Altretamine",
      "Activation is described, but the DNA adduct chemistry is not established"
    ],
    [
      "Belinostat",
      "Acrylamide-like hydroxamic acid that chelates zinc"
    ],
    [
      "Benorilate",
      "Ester of aspirin and paracetamol; covalent action of the intact drug is not documented"
    ],
    [
      "Betaine",
      "Substrate"
    ],
    [
      "Cangrelor",
      "Reversible P2Y12 antagonist"
    ],
    [
      "Cinepazide",
      "Cinnamoyl amide, no covalent action"
    ],
    [
      "Cobicistat",
      "Mechanism-based CYP3A4 inactivation is a pharmacokinetic booster action, not an indication target"
    ],
    [
      "Crinecerfont",
      "Alkyne is not a warhead"
    ],
    [
      "Crisaborole",
      "Benzoxaborole that coordinates PDE4 metal ions; no covalent bond to the protein"
    ],
    [
      "Cycloserine",
      "Forms an adduct with the PLP cofactor, a freely dissociating coenzyme"
    ],
    [
      "Dutasteride",
      "Slow-binding; any covalent adduct is with NADPH, a freely dissociating coenzyme"
    ],
    [
      "Entacapone",
      "Nitrocatechol with a conjugated nitrile; reversible COMT inhibitor"
    ],
    [
      "Eptifibatide",
      "Cyclic peptide held by a disulfide; no covalent action"
    ],
    [
      "Estramustine phosphate",
      "Carbamate is stable; acts on microtubules and the estrogen receptor, not as an alkylator"
    ],
    [
      "Ethacrynic acid",
      "Michael acceptor that reacts with thiols, but covalent binding to NKCC2 is not established"
    ],
    [
      "Ethionamide",
      "Metabolite forms an adduct with NAD, a freely dissociating coenzyme"
    ],
    [
      "Evogliptin",
      "Non-covalent DPP-4 inhibitor"
    ],
    [
      "Ezetimibe",
      "Azetidinone that binds the NPC1L1 sterol transporter non-covalently"
    ],
    [
      "Finasteride",
      "Forms an NADP-dihydrofinasteride adduct with the coenzyme, not with the protein"
    ],
    [
      "Fomepizole",
      "Competitive alcohol dehydrogenase inhibitor"
    ],
    [
      "Foscarbidopa",
      "Hydrazine forms a hydrazone with PLP cofactor (prodrug of carbidopa)"
    ],
    [
      "Furazolidone",
      "Reactive nitroreduction metabolites act on many targets; no defined target bond"
    ],
    [
      "Hydroxyurea",
      "Quenches a tyrosyl radical of ribonucleotide reductase; no covalent bond to the target"
    ],
    [
      "Isoniazid",
      "Metabolite forms an adduct with NAD, a freely dissociating coenzyme"
    ],
    [
      "Linagliptin",
      "Non-covalent DPP-4 inhibitor"
    ],
    [
      "Methenamine",
      "Releases formaldehyde, which reacts with many biomolecules; no defined target"
    ],
    [
      "Metronidazole",
      "Radical anion damages DNA; no defined covalent adduct on a target"
    ],
    [
      "Montelukast",
      "Receptor antagonist"
    ],
    [
      "Nalfurafine",
      "Unsaturated amide in a morphinan; opioid receptor agonist"
    ],
    [
      "Nitisinone",
      "Tight-binding HPPD inhibitor; no covalent bond"
    ],
    [
      "Nitrofurantoin",
      "Reactive nitroreduction metabolites act on many targets; no defined target bond"
    ],
    [
      "Oxiglutatione",
      "Oxidized glutathione; redox substrate"
    ],
    [
      "Oxybutynin",
      "Alkyne is not a warhead; muscarinic antagonist"
    ],
    [
      "Panobinostat",
      "Acrylamide-like hydroxamic acid that chelates zinc"
    ],
    [
      "Pirtobrutinib",
      "Non-covalent BTK inhibitor"
    ],
    [
      "Pixantrone",
      "Topoisomerase II poison and intercalator; formaldehyde-mediated DNA adducts are minor"
    ],
    [
      "Pranlukast",
      "Receptor antagonist"
    ],
    [
      "Propiolactone",
      "Alkylating sterilant; no defined therapeutic target"
    ],
    [
      "Pyritinol",
      "Disulfide of pyridoxine; no covalent target action"
    ],
    [
      "Ritonavir",
      "Therapeutic target HIV protease is inhibited non-covalently"
    ],
    [
      "Romidepsin",
      "Disulfide prodrug; the reduced thiol binds zinc"
    ],
    [
      "Sitagliptin",
      "Non-covalent DPP-4 inhibitor"
    ],
    [
      "Sulfadicramide",
      "Sulfonamide antibacterial; the unsaturated amide is not reactive in this setting"
    ],
    [
      "Teneligliptin",
      "Non-covalent DPP-4 inhibitor"
    ],
    [
      "Terfenadine",
      "Receptor antagonist"
    ],
    [
      "Teriflunomide",
      "Cyanoenol that binds DHODH reversibly"
    ],
    [
      "Ticagrelor",
      "Reversible P2Y12 antagonist"
    ],
    [
      "Tiopronin",
      "Thiol that forms a soluble cystine mixed disulfide; no protein target"
    ],
    [
      "Trelagliptin",
      "Benzonitrile; non-covalent DPP-4 inhibitor"
    ],
    [
      "Vonoprazan",
      "Potassium-competitive acid blocker; reversible"
    ],
    [
      "Warfarin",
      "Reversible inhibitor of VKORC1"
    ],
    [
      "Zafirlukast",
      "Receptor antagonist"
    ]
  ],
  "kinaseL01ECovalent": 12,
  "kinaseL01EApprovedSince2013": 57,
  "kinaseL01ECovalentSince2013": 12,
  "decadeTable": [
    {
      "decade": "Before 1950",
      "allApproved": 43,
      "broad": 2,
      "strict": 0,
      "broadWithoutBetaLactams": 1,
      "broadPct": 4.7,
      "strictPct": 0.0,
      "broadWithoutBetaLactamsPct": 2.3
    },
    {
      "decade": "1950s",
      "allApproved": 140,
      "broad": 13,
      "strict": 0,
      "broadWithoutBetaLactams": 12,
      "broadPct": 9.3,
      "strictPct": 0.0,
      "broadWithoutBetaLactamsPct": 8.6
    },
    {
      "decade": "1960s",
      "allApproved": 143,
      "broad": 11,
      "strict": 0,
      "broadWithoutBetaLactams": 8,
      "broadPct": 7.7,
      "strictPct": 0.0,
      "broadWithoutBetaLactamsPct": 5.6
    },
    {
      "decade": "1970s",
      "allApproved": 172,
      "broad": 20,
      "strict": 0,
      "broadWithoutBetaLactams": 4,
      "broadPct": 11.6,
      "strictPct": 0.0,
      "broadWithoutBetaLactamsPct": 2.3
    },
    {
      "decade": "1980s",
      "allApproved": 349,
      "broad": 36,
      "strict": 1,
      "broadWithoutBetaLactams": 8,
      "broadPct": 10.3,
      "strictPct": 0.3,
      "broadWithoutBetaLactamsPct": 2.3
    },
    {
      "decade": "1990s",
      "allApproved": 305,
      "broad": 19,
      "strict": 2,
      "broadWithoutBetaLactams": 11,
      "broadPct": 6.2,
      "strictPct": 0.7,
      "broadWithoutBetaLactamsPct": 3.6
    },
    {
      "decade": "2000s",
      "allApproved": 233,
      "broad": 17,
      "strict": 5,
      "broadWithoutBetaLactams": 14,
      "broadPct": 7.3,
      "strictPct": 2.1,
      "broadWithoutBetaLactamsPct": 6.0
    },
    {
      "decade": "2010s",
      "allApproved": 268,
      "broad": 24,
      "strict": 16,
      "broadWithoutBetaLactams": 21,
      "broadPct": 9.0,
      "strictPct": 6.0,
      "broadWithoutBetaLactamsPct": 7.8
    },
    {
      "decade": "2020s",
      "allApproved": 152,
      "broad": 17,
      "strict": 11,
      "broadWithoutBetaLactams": 13,
      "broadPct": 11.2,
      "strictPct": 7.2,
      "broadWithoutBetaLactamsPct": 8.6
    }
  ],
  "since2010": {
    "allApproved": 420,
    "strict": 27,
    "broad": 41
  },
  "ruleOfFive": {
    "allApproved": {
      "n": 2104,
      "alertPct": 13.4
    },
    "broad": {
      "n": 173,
      "alert": 30,
      "alertPct": 17.3
    },
    "broadWithoutBetaLactams": {
      "n": 101,
      "alert": 10
    },
    "strict": {
      "n": 36,
      "alert": 7,
      "alertPct": 19.4
    },
    "strictMedianMw": 454.49
  },
  "window2012To2021": {
    "allApproved": 302,
    "strict": 17,
    "broad": 27
  },
  "warheadPatternHits": {
    "acrylamide": 21,
    "propiolamide / butynamide": 2,
    "cyanoacrylamide": 2,
    "terminal enone or acrylate": 1,
    "vinyl sulfone or sulfonamide": 0,
    "fumarate ester": 3,
    "alpha-halo ketone or amide": 0,
    "nitrile": 13,
    "boronic acid or oxaborole": 5,
    "aldehyde": 2,
    "epoxide": 2,
    "aziridine": 2,
    "beta-lactam": 73,
    "beta-lactone": 2,
    "diazabicyclooctane (N-sulfooxy urea)": 3,
    "sulfonyl halide": 0,
    "disulfide": 5,
    "thiol": 2,
    "2-haloethylamine": 13,
    "alkyl sulfonate": 2,
    "nitrosourea": 3,
    "triazene": 1,
    "hydrazine": 5,
    "propargylamine": 5,
    "cyclopropylamine": 3,
    "aryl carbamate": 7,
    "aryl ester (acyl donor)": 6,
    "phosphate or phosphonate ester with leaving group": 8,
    "sulfinyl benzimidazole": 0,
    "thienopyridine": 3,
    "ketoamide or trifluoromethyl ketone": 5,
    "quinone": 1,
    "isothiocyanate": 0,
    "nitroso": 5
  }
}