KRAS G12D inhibitor 22 (compound 6) is a KRAS mutation inhibitor with high antitumor activity (IC50 < 100 nM), excellent selectivity, and low toxicity. It is applicable in breast cancer research.

KRas (G12D):<100 nM

KRAS G12D inhibitor 22 effectively inhibits the growth of AGS cells (0.08-20 μM; 72 h) with an IC50 of less than 500 nM. It shows significant inhibitory activity against the KRAS G12D protein with an IC50 of less than 100 nM. Additionally, KRAS G12D inhibitor 22 demonstrates superior antiproliferative activity on ASPC-1 and AGS cells compared to MRTX1133, while offering better selectivity for other Kras G12C mutant cell lines.

After a single administration of KRAS G12D inhibitor 22 (3, 5 mg/kg; i.v. and i.p.; 0-24 h), the compound reaches effective concentrations for inhibiting tumor cell growth and demonstrates favorable bioavailability in SD rats.