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Pan KRas-IN-1 is a pan KRas inhibitor, can be used for agent resistance in cancer developed with KRas G12C inhibitors
In Vitro
Pan KRas-IN-1 (example 5) shows high binding capacity to KRas, with IC 50 s of <2 nM among different KRas isform, including G12D, G12V, G12R, G12A, G12S, G13D, Q61H, and WT. Pan KRas-IN-1 inhibits the phosphorylation of ERK downstream of KRas in different cells; AsPC-1 (G12D, IC 50 =9 nM), A549 (G12S, IC 50 =11 nM), HCT116 (G13D, IC 50 =23 nM), NCI-H358 (G12C, IC 50 =6 nM), NCI-H460 (Q61H, IC 50 =12 nM), NCI-H727 (G12V, IC 50 =29 nM), MKN1 (WT, IC 50 =32 nM), PSN-1 (G12R, IC 50 =681 nM). Pan KRas-IN-1 (0-3000 nM; 5 d) exhibits anti-proliferative activity against mutation of reststance to Adagrasib in mouse 3T3 fibroblasts, with IC 50 s 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). MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Form:Solid
IC50& Target:KRas G12D 9 nM (IC 50 ) KRas G12S 11 nM (IC 50 ) KRas G12C 6 nM (IC 50 ) KRas Q61H 12 mM (IC 50 ) KRas G12V 29 mM (IC 50 ) K-Ras WT 32 nM (IC 50 ) K-Ras G12R 681 nM (IC 50 ) K-Ras G13D 23 nM (IC 50 )