Pan KRas-IN-1

Pan KRas-IN-1 is a pan KRas inhibitor, can be used for drug resistance in cancer developed with KRas G12C inhibitors[1].

Research Areas >> Cancer

Signaling Pathways >> GPCR/G Protein >> Ras

KRas G12D:9 nM (IC50)

KRas G12S:11 nM (IC50)

KRas G12C:6 nM (IC50)

KRas Q61H:12 mM (IC50)

KRas G12V:29 mM (IC50)

K-Ras WT:32 nM (IC50)

K-Ras G12R:681 nM (IC50)

K-Ras G13D:23 nM (IC50)

Pan KRas-IN-1 (example 5) shows high binding capacity to KRas, with IC50s of <2 nM among different KRas isform, including G12D, G12V, G12R, G12A, G12S, G13D, Q61H, and WT[1]. Pan KRas-IN-1 inhibits the phosphorylation of ERK downstream of KRas in different cells; AsPC-1 (G12D, IC50=9 nM), A549 (G12S, IC50=11 nM), HCT116 (G13D, IC50=23 nM), NCI-H358 (G12C, IC50=6 nM), NCI-H460 (Q61H, IC50=12 nM), NCI-H727 (G12V, IC50=29 nM), MKN1 (WT, IC50=32 nM), PSN-1 (G12R, IC50=681 nM)[1]. Pan KRas-IN-1 (0-3000 nM; 5 d) exhibits anti-proliferative activity against mutation of reststance to Adagrasib (HY-130149, MRTX849) in mouse 3T3 fibroblasts, with IC50s of 32 nM (G12A), 28.1 nM (G12C), 20.25 nM (G12D), 1742 nM (G12R), 94 nM (G12V), 50 nM (G12W), 610 nM (G13D), 58 nM (Q61H)[1].

[1]. Wang Xiaolun, et al. Preparation of azaquinazoline pan-KRas inhibitors: World Intellectual Property Organization, WO2022132200[P]. 2022-06-23.