Opnurasib
drugOn this page
Also known as Jdq 443Jdq-443JDQ443Nvp-jdq-443
Summary
Opnurasib (CHEMBL5077861) is a phase-3 clinical-stage small molecule targeting KRAS; indicated across 4 conditions including non-small cell lung carcinoma and neoplasm.
At a glance
- Status: Max clinical phase 3 (not approved)
- Modality: Small molecule
- Targets: 1 (KRAS)
- Indications: 4 conditions
- Clinical trials: 8
- Chemistry: 526 Da · C29H28ClN7O
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL5077861 |
| Name | Opnurasib |
| Type | Small molecule |
| Max phase | 3 |
| FDA approved | no |
| PubChem CID | 156501355 |
| Molecular formula | C29H28ClN7O |
| Molecular weight | 526 |
| InChIKey | AZUYLZMQTIKGSC-UHFFFAOYSA-N |
SMILES: CC1=CC2=C(C=NN2)C(=C1Cl)C3=C(N(N=C3C4=CC5=C(C=C4)N(N=C5)C)C6CC7(C6)CN(C7)C(=O)C=C)C
IUPAC name: 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one
Also known as: Jdq 443, Jdq-443, JDQ443, Nvp-jdq-443, Opnurasib, OPNURASIB
Patent coverage: 203 distinct patent families (480 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 432 (90%) 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).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| KRAS | KRAS | Inhibition | 7.77 | 52.4% | P01116 |
Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: GTPase KRas, Cytochrome P450 2C9, Cytochrome P450 3A4.
Bioactivity
ChEMBL activities: 8 potent at pChembl ≥ 5 of 8 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| KRAS | 8 | IC50 | 10 | nM | CHEMBL_ACT_29078136 |
| KRAS | 7.77 | IC50 | 17 | nM | CHEMBL_ACT_24345411 |
| KRAS | 7.77 | IC50 | 17 | nM | CHEMBL_ACT_29050103 |
| KRAS | 7.7 | IC50 | 20 | nM | CHEMBL_ACT_25016555 |
| KRAS | 6.35 | IC50 | 444 | nM | CHEMBL_ACT_24345412 |
| KRAS | 6.35 | IC50 | 444 | nM | CHEMBL_ACT_29050106 |
| CYP2C9 | 5.43 | IC50 | 3740 | nM | CHEMBL_ACT_25016660 |
| CYP3A4 | 5.21 | IC50 | 6230 | nM | CHEMBL_ACT_25016658 |
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 |
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
4 indications (0 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).
| Indication | Trial phase | MONDO | EFO |
|---|---|---|---|
| non-small cell lung carcinoma | 3 | MONDO:0005233 | EFO:0003060 |
| neoplasm | 2 | MONDO:0005070 | EFO:0000616 |
| small cell lung carcinoma | 1 | MONDO:0008433 | EFO:0000702 |
| viral infectious disease | 1 | MONDO:0005108 | EFO:0000763 |
Clinical trials
Total trials: 8.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE1/PHASE2 | 3 |
| PHASE2 | 3 |
| PHASE3 | 1 |
| PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT05132075 | PHASE3 | ACTIVE_NOT_RECRUITING | Study of JDQ443 in Comparison With Docetaxel in Participants With Locally Advanced or Metastatic KRAS G12C Mutant Non-small Cell Lung Cancer |
| NCT04699188 | PHASE1/PHASE2 | ACTIVE_NOT_RECRUITING | Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation |
| NCT05358249 | PHASE1/PHASE2 | ACTIVE_NOT_RECRUITING | Platform Study of JDQ443 in Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation |
| NCT05445843 | PHASE2 | ACTIVE_NOT_RECRUITING | Study of Efficacy and Safety of JDQ443 Single-agent as First-line Treatment for Patients With Locally Advanced or Metastatic KRAS G12C- Mutated Non-small Cell Lung Cancer With a PD-L1 Expression < 1% or a PD-L1 Expression ≥ 1% and an STK11 Co-mutation. |
| NCT05714891 | PHASE2 | ACTIVE_NOT_RECRUITING | Neoadjuvant Platform Trial in Non-Small Cell Lung Cancer |
| NCT07468071 | PHASE1/PHASE2 | NOT_YET_RECRUITING | Rollover Study for Participants Who Have Been Treated With and Are Continuing to Benefit From Opnurasib as a Single Agent or in Combination With Other Study Treatments |
| NCT05999357 | PHASE2 | WITHDRAWN | JDQ443 for KRAS G12C NSCLC Brain Metastases |
| NCT05329623 | PHASE1 | COMPLETED | A Phase 1 Study to Evaluate the Pharmacokinetics of JDQ443 in Participants With Hepatic Impairment Compared to Matched Healthy Control 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.
7 molecules share ≥1 primary target. Top 7 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 |
| DIVARASIB | ChEMBL | Phase 2 | KRAS |
| GLECIRASIB | ChEMBL | Phase 2 | KRAS |
Related Atlas pages
- Genes: KRAS
- Diseases: non-small cell lung carcinoma
- Drugs: Adagrasib, Lonafarnib, Sotorasib, Dabrafenib, Vemurafenib