Opnurasib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Opnurasib (JDQ-443) (NVP-JDQ443) 是一种口服有效和选择性的共价 KRAS G12C 抑制剂。Opnurasib 具有抗肿瘤活性。

Opnurasib (JDQ-443) (NVP-JDQ443) is an orally active, potent, selective, and covalent KRAS G12C inhibitor (extracted from patent WO2021120890A1). Opnurasib shows antitumor activity.

Opnurasib (NVP-JDQ443) traps the GDP-bound inactive conformation of KRAS.?Opnurasib promotes dose-dependent reductions of phosphorylated ERK (pERK) levels and the proliferation of the KRASG12C-mutated cell lines NCI-H358 and NCI-H2122, with IC50 values of 0.018 and 0.063 μM, respectively.?Opnurasib covalently and selectively binds and inhibits GDP-bound KRASG12C with low reversible binding affinity to the RAS switch II pocket, and also inhibits proliferation of KRASG12C-mutated and KRAS G12C/H95, G12C/R68S, and G12C/Y96 double-mutant cell lines.Western Blot Analysis Cell Line:Ba/F3 cells Concentration:0, 0.3, 1 μM Incubation Time:30 min, 4 h Result:Inhibited signaling (pERK) and proliferation of the KRAS G12C/H95 double mutants G12C/H95R and G12C/H95Q.

Opnurasib (10-100 mg/kg, Orally, daily for 14 days) shows antitumor activity in KRAS G12C-mutated CDX models. 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. Opnurasib generates categorical antitumor responses in PDX models of NSCLC and colorectal tumors that are improved by combination treatment with other agents.Animal Model:KRAS G12C tumor-bearing nude mice (MIA PaCa-2 (PDAC); NCIH2122, LU99, HCC44, NCI-H2030 (NSCLC); and KYSE410 (esophageal cancer))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) 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).

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Others

Other Targets

Kras

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2653994-08-0

526.03

C29H28ClN7O

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 80 mg/mL (152.08 mM; 超声助溶 )

Cc1c(c(nn1C1CC2(C1)CN(C2)C(=O)C=C)-c1ccc2n(C)ncc2c1)-c1c(Cl)c(C)cc2[nH]ncc12

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(-20℃)

With Ice Pack

≥ 2 years