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Sotorasib

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Also known as AMG-510AMG510Kras g12c inhibitor 9Kras mutant-targeting amg 510LumakrasLumykras(R)-38(S)-AMG-510CT-AMG510AMG-510AMG510SOTORASIB (AMG510) RACEMATE

Summary

Sotorasib (CHEMBL4535757) is an approved small-molecule antineoplastic agent (ATC L01XX73) targeting KRAS; indicated across 7 conditions including neoplasm and non-small cell lung carcinoma; with CIViC clinical evidence for 13 variant-indication associations (e.g. KRAS G12C in lung non-small cell carcinoma).

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: L01XX73
  • Targets: 1 (KRAS)
  • Indications: 7 conditions
  • Clinical trials: 50
  • Precision-oncology evidence (CIViC): 13 variant–indication associations
  • Chemistry: 560.6 Da · C30H30F2N6O3

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL4535757
NameSotorasib
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID137278711
ChEBICHEBI:178199
ATCL01XX73
Molecular formulaC30H30F2N6O3
Molecular weight560.6
InChIKeyNXQKSXLFSAEQCZ-SFHVURJKSA-N

SMILES: C[C@H]1CN(CCN1C2=NC(=O)N(C3=NC(=C(C=C32)F)C4=C(C=CC=C4F)O)C5=C(C=CN=C5C(C)C)C)C(=O)C=C

IUPAC name: 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-propan-2-yl-3-pyridinyl)-4-[(2S)-2-methyl-4-prop-2-enoylpiperazin-1-yl]pyrido[2,3-d]pyrimidin-2-one

ChEBI definition: A pyridopyrimidine that is pyrido[2,3-d]pyrimidin-2(1H)-one substituted by 4-methyl-2-(propan-2-yl)pyridin-3-yl, (2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl, fluoro and 2-fluoro-6-hydroxyphenyl groups at positions 1, 4, 6 and 7, respectively. It is approved for the treatment of patients with non-small cell lung cancer having KRASG12C mutations.

Pharmacological roles (ChEBI): antineoplastic agent.

Also known as: AMG-510, AMG510, Kras g12c inhibitor 9, Kras mutant-targeting amg 510, Lumakras, Lumykras, Sotorasib, (R)-38, SOTORASIB, KRAS MUTANT-TARGETING AMG 510, LUMYKRAS, LUMAKRAS

Patent coverage: 1,693 distinct patent families (3,916 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 3,698 (94%) 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
KRASKRASInhibition52.4%P01116

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: GTPase KRas, SOS1-KRAS.

Bioactivity

ChEMBL activities: 6 potent at pChembl ≥ 5 of 8 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
KRAS8.02IC509.66nMCHEMBL_ACT_24886991
KRAS7.8IC5015.8nMCHEMBL_ACT_24970334
KRAS7.61IC5024.5nMCHEMBL_ACT_28708121
KRAS7.52IC5030nMCHEMBL_ACT_22760403
KRAS7.17IC5068nMCHEMBL_ACT_19057944
KRAS5.12IC507500nMCHEMBL_ACT_29055486

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

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

7 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
neoplasm4MONDO:0005070EFO:0000616
non-small cell lung carcinoma4MONDO:0005233EFO:0003060
colorectal neoplasm3MONDO:0005335MONDO:0005575
lung neoplasm2MONDO:0021117MONDO:0008903
ovarian carcinoma2MONDO:0005140EFO:0001075
liver disorder1MONDO:0005154EFO:0001421
exocrine pancreatic carcinoma1MONDO:0005192EFO:0002618

Clinical trials

Total trials: 50.

Phase distribution

PhaseTrials
PHASE217
PHASE117
PHASE1/PHASE28
PHASE34
Not specified2
PHASE41
EARLY_PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT06314763PHASE4COMPLETEDRivaroxaban Sotorasib Interaction Study
NCT05920356PHASE3RECRUITINGA Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
NCT06252649PHASE3RECRUITINGStudy of Sotorasib, Panitumumab and FOLFIRI Versus FOLFIRI With or Without Bevacizumab-awwb in Treatment-naïve Participants With Metastatic Colorectal Cancer With KRAS p.G12C Mutation
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
NCT05198934PHASE3COMPLETEDSotorasib and Panitumumab Versus Investigator’s Choice for Participants With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation
NCT03600883PHASE1/PHASE2ACTIVE_NOT_RECRUITINGA Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of Sotorasib (AMG 510) in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreaK 100)
NCT04092673PHASE1/PHASE2RECRUITINGStudy of eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies
NCT04625647PHASE2ACTIVE_NOT_RECRUITINGTesting the Use of Targeted Treatment (AMG 510) for KRAS G12C Mutated Advanced Non-squamous Non-small Cell Lung Cancer (A Lung-MAP Treatment Trial)
NCT05074810PHASE1/PHASE2ACTIVE_NOT_RECRUITINGPhase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients
NCT05398094PHASE2RECRUITINGClinical Trial of AMG510 in Stage III Unresectable NSCLC KRAS p.G12C Patients and Ineligible for Chemo-radiotherapy
NCT05564377PHASE2RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Patients With Locally Advanced or Advanced Solid Tumors, The ComboMATCH Screening Trial
NCT05638295PHASE2ACTIVE_NOT_RECRUITINGTesting the Use of AMG 510 (Sotorasib) and Panitumumab as a Targeted Treatment for KRAS G12C Mutant Solid Tumor Cancers (A ComboMATCH Treatment Trial)
NCT05845450PHASE2RECRUITINGPre-operative Targeted Treatments in Molecularly Selected Resectable Colorectal Cancer (UNICORN)
NCT06582771PHASE2RECRUITINGA Study of Sotorasib in People With Non-Small Cell Lung Cancer
NCT07012031PHASE1/PHASE2RECRUITINGSotorasib in Combination With Trastuzumab Deruxtecan for the Treatment of Locally Advanced and Metastatic Non-small Cell Lung Cancer With a KRAS G12C Mutation
NCT07172919PHASE2RECRUITINGA Rollover Study Evaluating Sotorasib With or Without Panitumumab in Participants With KRAS p.G12C Mutation
NCT07543172PHASE2NOT_YET_RECRUITINGCIMAvax-EGF With KRAS G12C Inhibitor for the Treatment of Advanced, KRAS G12C Mutated Non Small Cell Lung Cancer
NCT07563738PHASE1/PHASE2RECRUITINGA 2-part Phase 1/2 Open-label Trial on ODM-212
NCT04720976PHASE1/PHASE2COMPLETEDJAB-3312 Based Combination Therapy in Adult Patients With Advanced Solid Tumors
NCT04933695PHASE2COMPLETEDA Study of Sotorasib (AMG 510) in Participants With Stage IV NSCLC Whose Tumors Harbor a KRAS p.G12C Mutation in Need of First-line Treatment
NCT05054725PHASE2COMPLETEDCombination Study of RMC-4630 and Sotorasib for NSCLC Subjects With KRASG12C Mutation After Failure of Prior Standard Therapies
NCT05251038PHASE1/PHASE2WITHDRAWNStudy of Sotorasib Combined With Chemotherapy for Second Line Treatment of Pancreas Cancer
NCT05311709PHASE2UNKNOWNSotorasib in Advanced KRASG12C-mutated Non-small Cell Lung Cancer Patients With Comorbidities
NCT05313009PHASE1/PHASE2TERMINATEDTarlox and Sotorasib in Patients With KRAS G12C Mutations
NCT05400577PHASE2WITHDRAWNSotorasib in KRAS G12C Mutated, Resectable, Stage Ib-IIIA NSCLC
NCT05451056PHASE2UNKNOWNAn Open-label, Phase 2trial of Sotorasib in KRAS G12C-mutant Non-small-cell Lung Cancer(NSCLC) Patients and a Translational Study to Find Acquired Resistance Mechanism to Sotorasib
NCT05815186PHASE2WITHDRAWNLadarixin With Sotorasib in Advanced NSCLC - Phase II
NCT05993455PHASE2UNKNOWNA Phase 2 Basket Trial in Which Patients With Advanced Solid Tumors Carrying the KRAS G12C mUtation Receive Treatment With a Combination of Sotorasib and Panitumumab
NCT06068153PHASE2WITHDRAWNAMG510 (sotorasib) Plus Lenvatinib As Second-line Treatment in Patients with KRASG12C Mutant, Metastatic NSCLC
NCT06333678PHASE2COMPLETEDA Study Comparing Sotorasib With Durvalumab in People With Non-Small Cell Lung Cancer (NSCLC)
NCT04185883PHASE1ACTIVE_NOT_RECRUITINGSotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)
NCT05815173PHASE1RECRUITINGLadarixin With Sotorasib in Advanced NSCLC
NCT06249282PHASE1RECRUITINGCarfilzomib in Combination With Sotorasib for the Treatment of Patients With KRAS G12C Mutated Advanced or Metastatic Non-small Cell Lung Cancer
NCT06333951PHASE1ACTIVE_NOT_RECRUITINGAnvumetostat Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol) (MTAPESTRY 104).
NCT06804824PHASE1RECRUITINGA First-in-Human (FIH) Study to Evaluate the Safety and Tolerability of VVD-159642 in Participants With Advanced Solid Tumors
NCT06807619PHASE1RECRUITINGA Study of Sotorasib in People With Brain Tumors
NCT06892054PHASE1RECRUITINGSotorasib Combined With First-line Chemotherapy for Advanced Pancreatic Adenocarcinoma
NCT04887064PHASE1COMPLETEDPharmacokinetics of Sotorasib in Healthy Participants and Participants With Moderate or Severe Hepatic Impairment
NCT04892017PHASE1TERMINATEDStudy of Inlexisertib (DCC-3116) in Participants With RAS/MAPK Pathway Mutant Solid Tumors
NCT04959981PHASE1COMPLETEDA Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Advanced NSCLC

Clinical evidence (CIViC)

Variant × indication × effect (13 predictive associations from 17 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
KRAS G12CLung Non-small Cell CarcinomaSensitivity/ResponseSotorasibCIViC AEID9431 +4
KRAS G12CColorectal CancerSensitivity/ResponseSotorasib + PanitumumabCIViC AEID12264
KRAS G12CSolid Tumors, AdvancedSensitivity/ResponseSotorasibCIViC BEID10110
KRAS G12CPancreatic CancerSensitivity/ResponseSotorasibCIViC BEID11680
KRAS G12CCancerSensitivity/ResponseSotorasibCIViC BEID8068
KRAS G12CLung Non-small Cell CarcinomaSensitivity/ResponseSotorasib + AdagrasibCIViC DEID11521
KRAS G12CLung Non-small Cell CarcinomaSensitivity/ResponseSotorasib + AfatinibCIViC DEID9960
KRAS G12CLung Non-small Cell CarcinomaSensitivity/ResponseSotorasib + ErlotinibCIViC DEID9961
KRAS G12CLung Non-small Cell CarcinomaSensitivity/ResponseRMC-4550 + SotorasibCIViC DEID9962
KRAS G12CLung Non-small Cell CarcinomaSensitivity/ResponseSotorasib + TrametinibCIViC DEID9963
KRAS G12CLung Non-small Cell CarcinomaSensitivity/ResponseSotorasib + AMG511CIViC DEID9964
KRAS G12CLung Non-small Cell CarcinomaSensitivity/ResponseSotorasib + CarboplatinCIViC DEID9965
KRAS G12CCancerARS-1620 + Vociprotafib + SotorasibCIViC DEID8039

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
ADAGRASIBChEMBL + PubChemPhase 4 (approved)KRAS
LONAFARNIBChEMBL + 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
v1.1.2
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