BI-2865

• CAT Number: I041080
• CAS Number: 2937327-93-8
• Molecular Formula: C23H27N7O2S
• Molecular Weight: 465.57
• Purity: ≥95%
• Synonyms: (4S)-2-amino-4-methyl-4-[3-[4-[(1S)-1-[(2S)-1-methylpyrrolidin-2-yl]ethoxy]pyrimidin-2-yl]-1,2,4-oxadiazol-5-yl]-6,7-dihydro-5H-1-benzothiophene-3-carbonitrile
• InChI: InChI=1S/C23H27N7O2S/c1-13(15-6-5-11-30(15)3)31-17-8-10-26-20(27-17)21-28-22(32-29-21)23(2)9-4-7-16-18(23)14(12-24)19(25)33-16/h8,10,13,15H,4-7,9,11,25H2,1-3H3/t13-,15-,23-/m0/s1
• InChIKey: MIUFORKWYHBPRW-HMFCALDFSA-N
• SMILES: CC(C1CCCN1C)OC2=NC(=NC=C2)C3=NOC(=N3)C4(CCCC5=C4C(=C(S5)N)C#N)C

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].
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, as shown in Co-crystal structures of BI-2865 bound to KRAS[1].
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[1].

Reference

[1]. Kim D, et al. Pan-KRAS inhibitor disables oncogenic signalling and tumour growth. Nature. 2023 May 31.
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