KRAS inhibitor-10 (WO2021005165 A1, compound 11) is a potent and selective inhibitor of RAS proteins, with a specific focus on KRAS proteins. This orally active anti-cancer agent demonstrates strong efficacy in cancer research, specifically in pancreatic cancer, breast cancer, multiple myeloma, leukemia, and lung cancer. KRAS inhibitor-10 is classified as a tetrahydroisoquinoline compound. Its inhibitory properties provide valuable insights and potential therapeutic applications in the field of oncology [1].

KRAS inhibitor-10 (0.1-50 μμ; 72 hours) has antiproliferative effects in KRas mutant tumor cells, KRAS inhibitor-10 is against A549 (lung carcinoma cell line bearing KRasG12S oncogenic mutation), H358 (non-small cell lung cancer line bearing KRasG12C oncogenic mutation), PANC-1 (epithelioid carcinoma of the pancreas cell line bearing KRasG12D oncogenic mutation) and RPMI (myeloma cell line bearing KRasG12A oncogenic mutation) cell proliferation with IC50 values of 0.2 μM, 0.2 μM, 0.1 μM and 0.8 μM, respectively[1].KRAS inhibitor-10 (0-1 μM, 7 days) is against cell viability in a 3D CellTiter-GloTM cell viability assay for NIH-H358 cell, the IC50 value is 0.413 μM[1].

KRAS inhibitor-10 (oral administration; 20 mg/kg; BID; 27 days) is safe and tolerate for the bearing mice. KRAS inhibitor-10 demonstrates significant oral anti-tumor activities in vivo. And the tumor growth inhibition (TGI) value is 48.22% for KRAS inhibitor-10[1].