Olomorasib
drug drugOn this page
Also known as LY-3537982Ly3537982
Summary
Olomorasib (CHEMBL6068410) is a phase-3 clinical-stage small molecule targeting KRAS; indicated across 1 condition including neoplasm.
At a glance
- Status: Max clinical phase 3 (not approved)
- Modality: Small molecule
- Targets: 1 (KRAS)
- Indications: 1 condition
- Clinical trials: 14
- Chemistry: 529 Da · C25H19ClF2N4O3S
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL6068410 |
| Name | Olomorasib |
| Type | Small molecule |
| Max phase | 3 |
| FDA approved | no |
| PubChem CID | 156472638 |
| Molecular formula | C25H19ClF2N4O3S |
| Molecular weight | 529 |
| InChIKey | OZUPICRWMLEFCS-LBPRGKRZSA-N |
SMILES: C=CC(=O)N1CCN2[C@H](C1)CCOC3=C(C(=C(C=C3C2=O)F)C4=C5C(=C(SC5=C(C=C4)F)N)C#N)Cl
IUPAC name: 4-[(13aS)-10-chloro-8-fluoro-6-oxo-2-prop-2-enoyl-1,3,4,12,13,13a-hexahydropyrazino[2,1-d][1,5]benzoxazocin-9-yl]-2-amino-7-fluoro-1-benzothiophene-3-carbonitrile
Also known as: LY-3537982, Ly3537982, LY3537982, Olomorasib, OLOMORASIB
Patent coverage: 12 distinct patent families (22 SureChEMBL compound mentions), from 1 matched compound structure(s). 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).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| KRAS | KRAS | Inhibition | 9.02 | 52.4% | P01116 |
Bioactivity
No ChEMBL bioactivity rows at pChembl ≥ 5 (expected for biologics / antibodies).
Target pathways
Aggregated over 1 target gene(s): KRAS.
Top Reactome pathways
71 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| SOS-mediated signalling | 1 | KRAS |
| Activation of RAS in B cells | 1 | KRAS |
| Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants | 1 | KRAS |
| SHC1 events in ERBB2 signaling | 1 | KRAS |
| SHC1 events in ERBB4 signaling | 1 | KRAS |
| Signaling by SCF-KIT | 1 | KRAS |
| Signalling to RAS | 1 | KRAS |
| p38MAPK events | 1 | KRAS |
| GRB2 events in EGFR signaling | 1 | KRAS |
| SHC1 events in EGFR signaling | 1 | KRAS |
| Downstream signal transduction | 1 | KRAS |
| GRB2 events in ERBB2 signaling | 1 | KRAS |
| Tie2 Signaling | 1 | KRAS |
| EGFR Transactivation by Gastrin | 1 | KRAS |
| DAP12 signaling | 1 | KRAS |
| SHC-related events triggered by IGF1R | 1 | KRAS |
| FCERI mediated MAPK activation | 1 | KRAS |
| NCAM signaling for neurite out-growth | 1 | KRAS |
| Ca2+ pathway | 1 | KRAS |
| Ras activation upon Ca2+ influx through NMDA receptor | 1 | KRAS |
| VEGFR2 mediated cell proliferation | 1 | KRAS |
| CD209 (DC-SIGN) signaling | 1 | KRAS |
| Constitutive Signaling by EGFRvIII | 1 | KRAS |
| SHC-mediated cascade:FGFR1 | 1 | KRAS |
| FRS-mediated FGFR1 signaling | 1 | KRAS |
| SHC-mediated cascade:FGFR2 | 1 | KRAS |
| FRS-mediated FGFR2 signaling | 1 | KRAS |
| SHC-mediated cascade:FGFR3 | 1 | KRAS |
| FRS-mediated FGFR3 signaling | 1 | KRAS |
| FRS-mediated FGFR4 signaling | 1 | KRAS |
| SHC-mediated cascade:FGFR4 | 1 | KRAS |
| Signaling by FGFR2 in disease | 1 | KRAS |
| Signaling by FGFR4 in disease | 1 | KRAS |
| Signaling by FGFR1 in disease | 1 | KRAS |
| Signaling by FGFR3 in disease | 1 | KRAS |
| Regulation of RAS by GAPs | 1 | KRAS |
| RAF activation | 1 | KRAS |
| RAF/MAP kinase cascade | 1 | KRAS |
| MAP2K and MAPK activation | 1 | KRAS |
| Negative regulation of MAPK pathway | 1 | KRAS |
| Signaling by moderate kinase activity BRAF mutants | 1 | KRAS |
| Signaling by high-kinase activity BRAF mutants | 1 | KRAS |
| Signaling by BRAF and RAF1 fusions | 1 | KRAS |
| RAS signaling downstream of NF1 loss-of-function variants | 1 | KRAS |
| Paradoxical activation of RAF signaling by kinase inactive BRAF | 1 | KRAS |
| Insulin receptor signalling cascade | 1 | KRAS |
| PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases | 1 | KRAS |
| MET activates RAS signaling | 1 | KRAS |
| RUNX3 regulates p14-ARF | 1 | KRAS |
| Activated NTRK2 signals through RAS | 1 | KRAS |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| MAPK cascade | 1 |
| liver development | 1 |
| Ras protein signal transduction | 1 |
| female pregnancy | 1 |
| visual learning | 1 |
| response to gravity | 1 |
| gene expression | 1 |
| positive regulation of gene expression | 1 |
| glial cell proliferation | 1 |
| Rac protein signal transduction | 1 |
| cytokine-mediated signaling pathway | 1 |
| forebrain astrocyte development | 1 |
| actin cytoskeleton organization | 1 |
| negative regulation of epithelial cell differentiation | 1 |
| regulation of synaptic transmission, GABAergic | 1 |
Indications & clinical
Indications
1 disease 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) | Phase | MONDO | EFO |
|---|---|---|---|
| neoplasm | 1 | MONDO:0005070 | EFO:0000616 |
Clinical trials
Total trials: 14.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE1 | 10 |
| PHASE3 | 2 |
| PHASE1/PHASE2 | 2 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT06119581 | PHASE3 | RECRUITING | A Study of First-Line Olomorasib (LY3537982) and Pembrolizumab With or Without Chemotherapy in Patients With Advanced KRAS G12C-Mutant Non-small Cell Lung Cancer |
| NCT06890598 | PHASE3 | RECRUITING | Study of Olomorasib (LY3537982) in Combination With Standard of Care in Participants With Resected or Unresectable KRAS G12C-mutant Non-Small Cell Lung Cancer |
| NCT04956640 | PHASE1/PHASE2 | ACTIVE_NOT_RECRUITING | Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C) |
| NCT07227025 | PHASE1/PHASE2 | RECRUITING | A Study of Amivantamab and Olomorasib Combination Therapy in Participants With Metastatic Non-Small Cell Lung Cancer |
| NCT05824858 | PHASE1 | COMPLETED | A Study of the Effect of Food on LY3537982 in Healthy Participants |
| NCT05860933 | PHASE1 | COMPLETED | A Study of the Effects of Itraconazole or Carbamazepine on LY3537982 in Healthy Participants |
| NCT05901311 | PHASE1 | COMPLETED | A Study of [14C]-LY3537982 in Healthy Participants |
| NCT06111521 | PHASE1 | COMPLETED | A Drug-Drug Interaction Study of LY3537982 on Midazolam, Digoxin, and Rosuvastatin in Healthy Participants |
| NCT06235983 | PHASE1 | COMPLETED | A Study of LY3537982 in Chinese Participants With Advanced Solid Tumors |
| NCT06719128 | PHASE1 | COMPLETED | A Study of Olomorasib (LY3537982) in Participants With Hepatic Impairment and Healthy Participants |
| NCT07044271 | PHASE1 | COMPLETED | A Study of Multiple Olomorasib (LY3537982) Capsules in Healthy Participants |
| NCT07124013 | PHASE1 | COMPLETED | A Study of Olomorasib (LY3537982) in Healthy Japanese Participants |
| NCT07137689 | PHASE1 | COMPLETED | A Study of LY3537982 in Participants With Kidney Problems Compared With Participants With Normal Kidney Function |
| NCT07439250 | PHASE1 | COMPLETED | A Study of Olomorasib (LY3537982) in Healthy Participants |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No PharmGKB pharmacogenomic data curated for this drug.
Related molecules
Related molecules
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.
8 molecules share ≥1 primary target. Top 8 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| ADAGRASIB | ChEMBL + PubChem | Phase 4 (approved) | KRAS |
| LONAFARNIB | ChEMBL + PubChem | Phase 4 (approved) | KRAS |
| SOTORASIB | ChEMBL + PubChem | Phase 4 (approved) | KRAS |
| DABRAFENIB | ChEMBL | Phase 4 (approved) | KRAS |
| VEMURAFENIB | ChEMBL | Phase 4 (approved) | KRAS |
| OPNURASIB | ChEMBL | Phase 3 | KRAS |
| DIVARASIB | ChEMBL | Phase 2 | KRAS |
| GLECIRASIB | ChEMBL | Phase 2 | KRAS |
Related Atlas pages
- Genes: KRAS
- Drugs: Adagrasib, Lonafarnib, Sotorasib, Dabrafenib, Vemurafenib, Opnurasib