pan-kras-in-4

Pan-KRAS-IN-4 (compound 5) is a potent KRAS inhibitor, demonstrating IC50 values of 0.37 nM for Kras G12C and 0.19 nM for Kras G12V [1].

AMG410 is a non-covalent, dual-modality KRAS inhibitor effective against both GDP (OFF) and GTP (ON) binding, with Kd (GDP) of 1 nM and Kd (GTP) of 22 nM, capable of blocking KRAS independently of the cell cycle. AMG410 does not affect HRAS and NRAS2, and exhibits high potency against KRAS G12D, G12V, G12C, G13D, and other mutants, with an IC₅₀ of 1–4 nM. It induces tumour regression and reduces phosphorylated ERK levels in KRAS-mutant cancer models.

AMG410 diTFA is a non-covalent selective pan-KRAS inhibitor with IC50 values of 1-4 nM for KRAS G12D, KRAS G12V, and KRAS G13D. It exhibits over 100-fold selectivity for HRAS and NRAS. AMG410 diTFA is a dual inhibitor of both GTP (active) and GDP (inactive) states, with Kd values of 1 nM for the GDP state and 22 nM for the GTP state. The compound effectively blocks KRAS signaling without dependence on the cycling state and inhibits the proliferation of tumor cells with wild-type KRAS amplification. It is applicable for research in colorectal, pancreatic, and lung cancers.