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Opnurasib

產品活性：Opnurasib (JDQ-443) (NVP-JDQ443) 是一種口服有效和選擇性的共價 KRAS G12C 抑制劑。Opnurasib 具有抗腫瘤活性。

研究領域：GPCR/G Protein  |  Cell Cycle/DNA Damage

作用靶點：Ras  |  PERK

In Vitro: 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.

In Vivo: 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.

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