Uses
(S)-JDQ-443 is an isomer of JDQ-443 (HY-139612). JDQ-443 is an orally active, potent, selective, and covalent KRAS G12C inhibitor (extracted from patent WO2021120890A1). JDQ-443 shows antitumor activity[1][2].
in vivo
JDQ443 (10-100 mg/kg, Orally, daily for 14 days) shows antitumor activity and inhibits the growth of tumor in a dose-dependent manner in KRAS G12C-mutated CDX models[2].
JDQ443 (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].
JDQ443 generates categorical antitumor responses in PDX models of NSCLC and colorectal tumors that are improved by combination treatment with other agents[2].
References
[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. DOI:
10.1158/2159-8290.CD-22-0158
![2-Propen-1-one, 1-[6-[(4S)-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]- Structure](https://www.chemicalbook.com/CAS/20211123/GIF/2653994-10-4.gif)