MCB-294

C18329-1mg

Ras

Apoptosis

O[C@] (C1) (C) CCCN1C2=NC (OC ([2H]) ([2H]) C3 (CCC4) N4C/C (C3) =C (F) /F) =NC5=C (F) C (C6=C (C (C#C) =C (F) C=C7) C7=CC (O) =C6) =NC=C52

C34H29D2F4N5O3

MCB-294 is a pan-KRAS inhibitor that targets both active (GTP-bound) and inactive (GDP-bound) KRAS states, exhibiting Kd values of about 1 pM and 10 nM, respectively. It shows preferential inhibition of KRAS over NRAS and HRAS. The compound inhibits proliferation of hTERT-HPNE cells harboring G12D, G12C, G12V, G12S, G13D, and wild-type KRAS variants, with IC50 values around 700 nM. MCB-294 triggers apoptosis in KRAS-mutated tumors and demonstrates activity against KRASG12C inhibitor-resistant cancer cells while modulating the tumor immune microenvironment. This compound serves as a research tool for pancreatic, colorectal, and lung cancer investigations.