Description
BI-2865 is a none-covalent pan-KRAS Inhibitor. BI-2865 blocked nucleotide exchange to prevent the activation of wild-type KRAS and a broad range of KRAS mutants, including G12A/C/D/F/V/S, G13C/D, V14I, L19F, Q22K, D33E, Q61H, K117N and A146V/T. Inhibition of downstream signaling and proliferation was restricted to cancer cells harboring mutant KRAS, and drug treatment suppressed KRAS mutant tumor growth in mice without having a detrimental effect on animal weight.
Uses
BI-2865 is a none-covalent pan-KRAS Inhibitor. BI-2865 binds to WT, G12C, G12D, G12V and G13D mutant KRAS with KDs of 6.9, 4.5, 32, 26, 4.3 nM respectively. BI-2865 inhibits the proliferation of G12C, G12D or G12V mutant KRAS expressing BaF3 cells (mean IC50: roughly 140 nM)[1].
Biological Activity
BI-2865 is a non-covalent pan-KRAS inhibitor that binds to KRAS WT, G12C, G12D, G12V, and G13D mutants with Kd values of 6.9 nM, 4.5 nM, 32 nM, 26 nM, and 4.3 nM, respectively. It can be used in studies related to KRAS mutant tumors.
in vitro
BI-2865 is a derivative with a prolinol substituent and a pyrimidine linker. BI-2865 has direct ionic interaction with E62 and a water-mediated hydrogen bond network with the side chain of R68 and the main chain carbonyl of Q61.
BI-2865 (5 days) inhibits the proliferation of G12C, G12D, or G12V mutant KRAS expressing BaF3 cells in the presence of IL-13, with a mean IC50 of roughly 140?nM.
References
[1] Kim D, et al. Pan-KRAS inhibitor disables oncogenic signalling and tumour growth. Nature. 2023 May 31. DOI:
10.1038/s41586-023-06123-3
