| Identification | Back Directory | [Name]
2-Propen-1-one, 1-[6-[(4R)-4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl]-2-azaspiro[3.3]hept-2-yl]- | [CAS]
2653994-08-0 | [Synonyms]
JDQ-443
NVP-JDQ443
JDQ443?(NVP-JDQ443)
JDQ-443 (Synonyms: NVP-JDQ443)
2-Propen-1-one, 1-[6-[(4R)-4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl]-2-azaspiro[3.3]hept-2-yl]- | [Molecular Formula]
C29H28ClN7O | [MDL Number]
MFCD34578463 | [MOL File]
2653994-08-0.mol | [Molecular Weight]
526.04 |
| Chemical Properties | Back Directory | [Boiling point ]
737.3±60.0 °C(Predicted) | [density ]
1.46±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 250 mg/mL (475.26 mM; Need ultrasonic) | [form ]
Solid | [pka]
12.55±0.40(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
JDQ443 is a RAS GTPase family covalent inhibitor currently in phase II trial in patients with nonsmall cell lung cancer (NSCLC) harboring the KRASG12C mutation who have received at least one prior systemic therapy. | [General Description]
Class: non-kinase;
Treatment: KRAS(G12C) NSCLC;
Elimination half-life: 7 h | [in vivo]
Opnurasib (10-100 mg/kg, Orally, daily for 14 days) shows antitumor activity in KRAS G12C-mutated CDX models[2].
Opnurasib (Orally, 100 mg/kg, daily (JDQ443) + 7.5 mg/kg, twice daily (TNO155), for 36 days) shows greater cell growth inhibition or cell killing compared with single-agent JDQ443 when combined with TNO155[2].
Opnurasib generates categorical antitumor responses in PDX models of NSCLC and colorectal tumors that are improved by combination treatment with other agents[2]. | Animal Model: | KRAS G12C tumor-bearing nude mice (MIA PaCa-2 (PDAC); NCIH2122, LU99, HCC44, NCI-H2030 (NSCLC); and KYSE410 (esophageal cancer))[2] | | Dosage: | 10, 30, 100 mg/kg | | Administration: | Orally, daily for 14 days | | Result: | Inhibited the growth of all models in a dose-dependent manner. |
| Animal Model: | Three KRAS G12C-mutated CDX models (LU99, NCI-H2030, and KYSE410)[2] | | Dosage: | 100 mg/kg (JDQ443) + 7.5 mg/kg (TNO155) | | Administration: | Orally, daily (JDQ443) or twice daily (TNO155), for 36 days | | Result: | Combined with TNO155, showed either greater tumor efficacy compared with each agent alone (H2030, KYSE410) or a delayed time to tumor progression (LU99). |
| [target]
Primary targets: KRAS(G12C) | [IC 50]
KRas G12C |
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