(Rac)-Opnurasib  (Synonyms: (Rac)-JDQ-443; (Rac)-NVP-JDQ443)

(Rac)-Opnurasib ((Rac)-JDQ-443; (Rac)-NVP-JDQ443) is the levorotomer of Opnurasib (HY-139612). Opnurasib is an orally active, potent, selective, and covalent KRAS G12C inhibitor (extracted from patent WO2021120890A1). Opnurasib shows antitumor activity^[1][2].

Opnurasib traps the GDP-bound inactive conformation of KRAS^[1].
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^[2].
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^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

526.03

C₂₉H₂₈ClN₇O

2653201-38-6

O=C(N1CC2(CC(C2)N3N=C(C(C4=C5C=NNC5=CC(C)=C4Cl)=C3C)C6=CC=C7C(C=NN7C)=C6)C1)C=C

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. LIU BO, et al. PYRAZOLYL DERIVATIVES USEFUL AS ANTI-CANCER AGENTS. Patent WO2021120890A1.

  [2]. Weiss A, Lorthiois E, Barys L, et al. Discovery, Preclinical Characterization, and Early Clinical Activity of JDQ443, a Structurally Novel, Potent and Selective, Covalent Oral Inhibitor of KRASG12C. Cancer Discov. 2022;candisc.0158.2022.  [Content Brief]