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Adagrasib

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Also known as Kras g12c inhibitor mrtx849KrazatiMrtx-849Mrtx849COMPOUND 20ADAGRASIB (MRTX849)

Summary

Adagrasib (CHEMBL4594350) is an approved small molecule (ATC L01XX77) targeting KRAS; indicated across 6 conditions including non-small cell lung carcinoma and neoplasm; with CIViC clinical evidence for 3 variant-indication associations (e.g. KRAS G12C in colorectal cancer).

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: L01XX77
  • Targets: 1 (KRAS)
  • Indications: 6 conditions
  • Clinical trials: 35
  • Precision-oncology evidence (CIViC): 3 variant–indication associations
  • Chemistry: 604.1 Da · C32H35ClFN7O2

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL4594350
NameAdagrasib
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID138611145
ATCL01XX77
Molecular formulaC32H35ClFN7O2
Molecular weight604.1
InChIKeyPEMUGDMSUDYLHU-ZEQRLZLVSA-N

SMILES: CN1CCC[C@H]1COC2=NC3=C(CCN(C3)C4=CC=CC5=C4C(=CC=C5)Cl)C(=N2)N6CCN([C@H](C6)CC#N)C(=O)C(=C)F

IUPAC name: 2-[(2S)-4-[7-(8-chloronaphthalen-1-yl)-2-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]-1-(2-fluoroprop-2-enoyl)piperazin-2-yl]acetonitrile

Also known as: Adagrasib, Kras g12c inhibitor mrtx849, Krazati, Mrtx-849, MRTX-849, Mrtx849, MRTX849, COMPOUND 20, ADAGRASIB, KRAZATI, KRAS G12C INHIBITOR MRTX849, ADAGRASIB (MRTX849)

Patent coverage: 1,244 distinct patent families (2,814 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 2,618 (93%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
KRASKRASInhibition5.4352.4%P01116

Broader ChEMBL bioactivity targets: 4 (assay-derived). Sample: GTPase KRas, CDK7/Cyclin H/MNAT1, von Hippel-Lindau disease tumor suppressor/GTPase KRas, SOS1-KRAS.

Bioactivity

ChEMBL activities: 16 potent at pChembl ≥ 5 of 16 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
CDK78.89IC501.3nMCHEMBL_ACT_24703132
KRAS8.3IC505nMCHEMBL_ACT_20638316
KRAS8.3IC505nMCHEMBL_ACT_26123572
KRAS8IC5010nMCHEMBL_ACT_22760405
KRAS8EC5010nMCHEMBL_ACT_24861639
KRAS8IC5010nMCHEMBL_ACT_29055481
KRAS7.85IC5014nMCHEMBL_ACT_20638198
KRAS6.89IC50130nMCHEMBL_ACT_25706479
KRAS6.88IC50133nMCHEMBL_ACT_29202757
KRAS6.6EC50250nMCHEMBL_ACT_24958961
KRAS6.6EC50250nMCHEMBL_ACT_24958962
KRAS6.6EC50250nMCHEMBL_ACT_24958963
KRAS6.6EC50250nMCHEMBL_ACT_24958964
KRAS6.6EC50250nMCHEMBL_ACT_24958965
KRAS5.43Ki3700nMCHEMBL_ACT_20638324
KRAS5.43Ki3700nMCHEMBL_ACT_24842017

Target pathways

Aggregated over 1 target gene(s): KRAS.

Top Reactome pathways

71 total, by targets touching each:

PathwayTargetsGenes
SOS-mediated signalling1KRAS
Activation of RAS in B cells1KRAS
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants1KRAS
SHC1 events in ERBB2 signaling1KRAS
SHC1 events in ERBB4 signaling1KRAS
Signaling by SCF-KIT1KRAS
Signalling to RAS1KRAS
p38MAPK events1KRAS
GRB2 events in EGFR signaling1KRAS
SHC1 events in EGFR signaling1KRAS
Downstream signal transduction1KRAS
GRB2 events in ERBB2 signaling1KRAS
Tie2 Signaling1KRAS
EGFR Transactivation by Gastrin1KRAS
DAP12 signaling1KRAS
SHC-related events triggered by IGF1R1KRAS
FCERI mediated MAPK activation1KRAS
NCAM signaling for neurite out-growth1KRAS
Ca2+ pathway1KRAS
Ras activation upon Ca2+ influx through NMDA receptor1KRAS
VEGFR2 mediated cell proliferation1KRAS
CD209 (DC-SIGN) signaling1KRAS
Constitutive Signaling by EGFRvIII1KRAS
SHC-mediated cascade:FGFR11KRAS
FRS-mediated FGFR1 signaling1KRAS
SHC-mediated cascade:FGFR21KRAS
FRS-mediated FGFR2 signaling1KRAS
SHC-mediated cascade:FGFR31KRAS
FRS-mediated FGFR3 signaling1KRAS
FRS-mediated FGFR4 signaling1KRAS
SHC-mediated cascade:FGFR41KRAS
Signaling by FGFR2 in disease1KRAS
Signaling by FGFR4 in disease1KRAS
Signaling by FGFR1 in disease1KRAS
Signaling by FGFR3 in disease1KRAS
Regulation of RAS by GAPs1KRAS
RAF activation1KRAS
RAF/MAP kinase cascade1KRAS
MAP2K and MAPK activation1KRAS
Negative regulation of MAPK pathway1KRAS
Signaling by moderate kinase activity BRAF mutants1KRAS
Signaling by high-kinase activity BRAF mutants1KRAS
Signaling by BRAF and RAF1 fusions1KRAS
RAS signaling downstream of NF1 loss-of-function variants1KRAS
Paradoxical activation of RAF signaling by kinase inactive BRAF1KRAS
Insulin receptor signalling cascade1KRAS
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases1KRAS
MET activates RAS signaling1KRAS
RUNX3 regulates p14-ARF1KRAS
Activated NTRK2 signals through RAS1KRAS

Dominant GO biological processes

GO termTargets
MAPK cascade1
liver development1
Ras protein signal transduction1
female pregnancy1
visual learning1
response to gravity1
gene expression1
positive regulation of gene expression1
glial cell proliferation1
Rac protein signal transduction1
cytokine-mediated signaling pathway1
forebrain astrocyte development1
actin cytoskeleton organization1
negative regulation of epithelial cell differentiation1
regulation of synaptic transmission, GABAergic1

Indications & clinical

Indications

2 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

IndicationPhaseMONDOEFO
non-small cell lung carcinoma4MONDO:0005233EFO:0003060
neoplasm4MONDO:0005070EFO:0000616

4 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)PhaseMONDOEFO
metastatic neoplasm1MONDO:0024883EFO:0009709
lung neoplasm1MONDO:0021117MONDO:0008903
malignant pancreatic neoplasm1MONDO:0009831EFO:1000359
colorectal neoplasm1MONDO:0005335MONDO:0005575

Clinical trials

Total trials: 35.

Phase distribution

PhaseTrials
PHASE116
PHASE28
PHASE34
PHASE1/PHASE24
PHASE2/PHASE31
EARLY_PHASE11
Not specified1

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04613596PHASE2/PHASE3RECRUITINGPhase 2 Trial of Adagrasib Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination in Patients With a KRAS G12C Mutation KRYSTAL-7
NCT04685135PHASE3ACTIVE_NOT_RECRUITINGPhase 3 Study of MRTX849 (Adagrasib) vs Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation
NCT04793958PHASE3ACTIVE_NOT_RECRUITINGPhase 3 Study of MRTX849 With Cetuximab vs Chemotherapy in Patients With Advanced Colorectal Cancer With KRAS G12C Mutation (KRYSTAL-10)
NCT06497556PHASE3ACTIVE_NOT_RECRUITINGA Study Evaluating the Efficacy and Safety of Divarasib Versus Sotorasib or Adagrasib in Participants With Previously Treated KRAS G12C-positive Advanced or Metastatic Non-Small Cell Lung Cancer
NCT06875310PHASE3RECRUITINGA Study of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4)
NCT03785249PHASE1/PHASE2ACTIVE_NOT_RECRUITINGPhase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1
NCT03994796PHASE2ACTIVE_NOT_RECRUITINGGenetic Testing in Guiding Treatment for Patients With Brain Metastases
NCT05673187PHASE2ACTIVE_NOT_RECRUITINGAdagrasib in Patients With KRASG12C-mutant NSCLC Who Are Elderly or Have Poor Performance Status
NCT05853575PHASE2ACTIVE_NOT_RECRUITINGTrial of Two Adagrasib Dosing Regimens in NSCLC With KRAS G12C Mutation (KRYSTAL 21)
NCT06248606PHASE2RECRUITINGAdagrasib + SRS for Patients With Metastatic KRAS G12C-mutated NSCLC With Untreated Brain Metastases
NCT06412198PHASE1/PHASE2RECRUITINGA Multicenter Phase 1b/2 Study of Adagrasib, Cetuximab, and Cemiplimab for Metastatic Colorectal Cancer Harboring KRAS G12C Mutations
NCT07288034PHASE2RECRUITINGImmunotherapy Biomarkers to Predict First-line PD(L)1-based Immunotherapy Response and Selection of Second-line Treatment in Stage IIIB-IV Non-small Cell Lung Cancer, IMMUNO-BIOMAP Trial
NCT07415031PHASE2RECRUITINGA Solid Tumor Study for Long Term Treatment of Cancer Patients Who Participated in Adagrasib Studies
NCT07543172PHASE2NOT_YET_RECRUITINGCIMAvax-EGF With KRAS G12C Inhibitor for the Treatment of Advanced, KRAS G12C Mutated Non Small Cell Lung Cancer
NCT04418661PHASE1/PHASE2TERMINATEDSafety and Efficacy Study of Vociprotafib (SAR442720) in Combination With Other Agents in Advanced Malignancies
NCT05472623PHASE2WITHDRAWNNeoadjuvant KRAS G12C Directed Therapy With Adagrasib (MRTX849) With or Without Nivolumab
NCT06024174PHASE1/PHASE2TERMINATEDA Study of BMS-986466 With Adagrasib With or Without Cetuximab in Participants With Kirsten Rat Sarcoma Virus Glycine 12 to Cysteine (KRAS G12C)-Mutant Solid Tumors
NCT05722327PHASE1ACTIVE_NOT_RECRUITINGPhase I Trial of Adagrasib (MRTX849) in Combination With Cetuximab and Irinotecan in Patients With Colorectal Cancer
NCT06026410PHASE1RECRUITINGKO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors
NCT06764771PHASE1ACTIVE_NOT_RECRUITINGA Study of BMS-986488 as Monotherapy and Combination Therapy in Participants With Advanced Malignant Tumors
NCT07382726PHASE1NOT_YET_RECRUITINGPhase 1 Study Of Izalontamab Brengitecan + Adagrasib In NSCLC - The IZA-A Trial
NCT04330664PHASE1COMPLETEDAdagrasib in Combination With TNO155 in Patients With Cancer (KRYSTAL 2)
NCT04975256PHASE1TERMINATEDAdagrasib in Combination With BI 1701963 in Patients With Cancer (KRYSTAL 14)
NCT05178888PHASE1COMPLETEDAdagrasib in Combination With Palbociclib in Patients With Advanced Solid Tumors (KRYSTAL-16)
NCT05263986PHASE1UNKNOWNThe Clinical Trial to Evaluate the Pharmacokinetics and Safety of MRTX849 in Patients With Advanced Solid Tumors
NCT05578092PHASE1TERMINATEDA Phase 1 Study of MRTX0902 in Solid Tumors With Mutations in the KRAS MAPK Pathway
NCT05634525PHASE1WITHDRAWNPhase Ib Trial of the KRASG12C Inhibitor Adagrasib (MRTX849) in KRAS G12C Mutant Metastatic Pancreatic Cancer Patients
NCT05840510PHASE1TERMINATEDAdagrasib in Combination With Nab-Sirolimus in Patients With Advanced Solid Tumors and Non-Small Cell Lung Cancer With a KRAS G12C Mutation (KRYSTAL -19)
NCT05848843PHASE1WITHDRAWNA Phase I Study of Adagrasib and Durvalumab for Treatment of Advanced Non-small Cell Lung Cancers and Gastro-intestinal Cancers Harboring KRAS G12C Mutations
NCT05924152PHASE1COMPLETEDA PK Study to Assess the Drug-drug Interaction of a BCRP Inhibitor on Adagrasib
NCT06039384PHASE1TERMINATEDA Study of INCB099280 in Combination With Adagrasib in Adults With Advanced Solid Tumors Harboring a KRASG12C Mutation
NCT06130254PHASE1TERMINATEDPhase Ib Trial of the KRAS G12C Inhibitor Adagrasib (MRTX849) in Combination With the PARP Inhibitor Olaparib in Patients With KRAS G12C Mutated Advanced Solid Tumors, With a Focus on Gynecological, Breast, Pancreatic and KEAP1 Mutated Non-small Cell Lung Cancers
NCT06801418PHASE1COMPLETEDBioequivalence Study Between Adagrasib Reference Tablets and High Drug Load Tablets
NCT07318389EARLY_PHASE1NOT_YET_RECRUITINGASCEND-CRC: Profiling and Targeting Dynamic Tumor Resistance in Patients With Metastatic Colorectal Cancer
NCT05162443Not specifiedAPPROVED_FOR_MARKETINGExpanded Access of Adagrasib (MRTX849) in Patients With Advanced Solid Tumors Who Have a KRAS G12C Mutation

Clinical evidence (CIViC)

Variant × indication × effect (3 predictive associations from 3 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
KRAS G12CColorectal CancerSensitivity/ResponseCetuximab + AdagrasibCIViC AEID12063
KRAS G12CLung Non-small Cell CarcinomaSensitivity/ResponseSotorasib + AdagrasibCIViC DEID11521
KRAS G12CSolid TumorSensitivity/ResponseAdagrasibCIViC DEID7572

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

7 molecules share ≥1 primary target. Top 7 by shared-target count:

MoleculeSourceStatusShared targets
LONAFARNIBChEMBL + PubChemPhase 4 (approved)KRAS
SOTORASIBChEMBL + PubChemPhase 4 (approved)KRAS
DABRAFENIBChEMBLPhase 4 (approved)KRAS
VEMURAFENIBChEMBLPhase 4 (approved)KRAS
OPNURASIBChEMBLPhase 3KRAS
DIVARASIBChEMBLPhase 2KRAS
GLECIRASIBChEMBLPhase 2KRAS

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.4
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot