adagrasib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
Ras protein inhibitors 5694 2326521-71-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • adagrasib
  • krazati
  • MRTX849
Adagrasib is an irreversible inhibitor of KRAS G12C that covalently binds to the mutant cysteine in KRAS G12C and locks the mutant KRAS protein in its inactive state that prevents downstream signaling without affecting wild-type KRAS protein. Adagrasib inhibits tumor cell growth and viability in cells harboring KRAS G12C mutations and results in tumor regression in KRAS G12C-mutated tumor xenograft models with minimal off-target activity.
  • Molecular weight: 604.13
  • Formula: C32H35ClFN7O2
  • CLOGP: 5.82
  • LIPINSKI: 1
  • HAC: 9
  • HDO: 0
  • TPSA: 88.83
  • ALOGS: -4.72
  • ROTB: 7
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.652 High 0.88
caco2-efflux Caco-2 efflux ratio (BA/AB) 6.761 High 0.88
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 9.638 10^-6 cm/s High 0.88
dh-clint Dog hepatocyte intrinsic clearance 12.246 uL/min/10^6 cells High 0.88
dppb Dog plasma protein binding (% unbound) 1.900 % High 0.88
fcs-ppb Fetal calf serum protein binding (% unbound) 8.340 % High 0.88
herg hERG pIC50 5.714 pIC50 High 0.88
hh-clint Human hepatocyte intrinsic clearance 9.226 uL/min/10^6 cells High 0.88
hlm-clint Human liver microsomal intrinsic clearance 68.077 uL/min/mg protein High 0.88
hppb Human plasma protein binding (% unbound) 2.490 % High 0.88
kinase-safety-class ACVR2B,BRAF,CAMK2D,EGFR,EIF2AK3,ERBB2,GRK2,ITK,MAPK10,MET,PDK1,PDK2,PDK4 13
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 13.122 High 0.88
mh-clint Mouse hepatocyte intrinsic clearance 48.641 High 0.88
mppb Mouse plasma protein binding (% unbound) 1.460 High 0.88
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 50.933 High 0.88
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 4.530 % High 0.88
rat-kpuu-brain Rat brain Kpuu 0.006 % High 1
rh-clint Rat hepatocyte intrinsic clearance 20.559 uL/min/10^6 cells High 0.88
rh-fuinc Rat hepatocyte fraction unbound in incubation 6.200 % High 0.88
rppb Rat plasma protein binding (% unbound) 2.110 % High 0.88
solubility-dd Solubility at pH 7.4 in DMSO 63.533 uM High 0.88

Approvals:

DateAgencyCompanyOrphan
Dec. 12, 2022 FDA MIRATI THERAPEUTICS, INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Death 178.58 83.52 66 297 456485 90171599

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Death 99.76 39.30 52 242 471133 42149908

FDA Adverse Event Reporting System (Geriatric)

None

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01XX77 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Other antineoplastic agents
MeSH PA D000970 Antineoplastic Agents

Related Drugs by ATC class:

L01XX Other antineoplastic agents 33 drugs
afliberceptaltretamineamsacrineanagrelidearsenic trioxideasparaginasebelzutifancalaspargase pegolcelecoxibdarinaparsindenileukin diftitoxeflornithine show all 33 →

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer indication 254637007 DOID:3908




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
200MG KRAZATI BRISTOL N216340 Dec. 12, 2022 RX TABLET ORAL 10689377 May 17, 2037 TREATMENT, IN COMBINATION WITH CETUXIMAB, OF ADULT PATIENTS WITH KRAS G12C-MUTED LOCALLY ADVANCED OR METASTATIC COLORECTAL CANCER, PER FDA APPROVED TEST, WHERE PRIOR TREATMENT WITH FLUOROPYRIMIDINE-, OXALIPLATIN-, AND IRINOTECAN-BASED CHEMOTHERAPY
200MG KRAZATI BRISTOL N216340 Dec. 12, 2022 RX TABLET ORAL 10689377 May 17, 2037 TREATMENT OF ADULT PATIENTS WITH KRAS G12C-MUTATED LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC), AS DETERMINED BY AN FDA APPROVED TEST, WHO HAVE RECEIVED AT LEAST ONE PRIOR SYSTEMIC THERAPY
200MG KRAZATI BRISTOL N216340 Dec. 12, 2022 RX TABLET ORAL 12336995 Feb. 5, 2041 TREATMENT, IN COMBINATION WITH CETUXIMAB, OF ADULT PATIENTS WITH KRAS G12C-MUTED LOCALLY ADVANCED OR METASTATIC COLORECTAL CANCER, PER FDA APPROVED TEST, WHERE PRIOR TREATMENT WITH FLUOROPYRIMIDINE-, OXALIPLATIN-, AND IRINOTECAN-BASED CHEMOTHERAPY

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
200MG KRAZATI BRISTOL N216340 Dec. 12, 2022 RX TABLET ORAL Dec. 12, 2027 NEW CHEMICAL ENTITY
200MG KRAZATI BRISTOL N216340 Dec. 12, 2022 RX TABLET ORAL Dec. 12, 2029 TREATMENT OF ADULT PATIENTS WITH KRAS G12C-MUTATED LOCALLY ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC), AS DETERMINED BY AN FDA-APPROVED TEST, WHO HAVE RECEIVED AT LEAST ONE PRIOR SYSTEMIC THERAPY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
GTPase KRas Enzyme INHIBITOR IC50 7.85 SCIENTIFIC LITERATURE DRUG LABEL

External reference:

IDSource
CHEMBL4594350 ChEMBL_ID
C000718190 MESH_SUPPLEMENTAL_RECORD_UI
10888 IUPHAR_LIGAND_ID
DB15568 DRUGBANK_ID
4041908 VANDF
C5544276 UMLSCUI
CHEBI:233309 CHEBI
A1B7W PDB_CHEM_ID
11519 INN_ID
D12301 KEGG_DRUG
138611145 PUBCHEM_CID
364307 MMSL
41146 MMSL
d09956 MMSL
019248 NDDF
8EOO6HQF8Y UNII
2625882 RXNORM
8EOO6HQF8Y INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
KRAZATI HUMAN PRESCRIPTION DRUG LABEL 1 80739-812 TABLET, COATED 200 mg ORAL NDA 29 sections