BI-907828

BI-907828 is an inhibitor of the protein-protein interaction between p53 and murine double minute 2 (MDM2, IC50 = 2 nM in a cell-free assay). It is selective for the p53-MDM2 interaction over the p53-MDMX interaction (IC50 = 7,944 nM). BI-907828 selectively inhibits the proliferation of Colon-26 colon cancer cells, which express wild-type p53, over 4T1 breast and MC-38 colon cancer cells, which express mutant p53 (IC50s = 259, 5,579, and 9,782 nM, respectively). It inhibits the proliferation of SJSA-1 osteosarcoma cells, BJ human foreskin fibroblasts, and hTERT RPE-1 retinal pigment epithelial cells but only induces apoptosis in SJSA-1 cells. BI-907828 induces tumor regression in an SJSA-1 mouse xenograft model and patient-derived xenograft (PDX) models. InChI: InChI=1S/C31H25Cl2FN4O3/c1-14-17(29(39)40)8-9-18-23-12-24-28(38(23)36-27(14)18)25(19-3-2-4-21(33)26(19)34)31(37(24)13-15-5-6-15)20-10-7-16(32)11-22(20)35-30(31)41/h2-4,7-11,15,24-25,28H,5-6,12-13H2,1H3,(H,35,41)(H,39,40)/t24-,25-,28+,31+/m0/s1 InChIKey: AMTXDBGKYPDTTA-SJVQGLCSSA-N SMILES: OC(C1=C(C)C2=NN([C@@]([C@]3([H])C4)([H])[C@H](C5=C(C(Cl)=CC=C5)F)[C@@]6(C7=CC=C(Cl)C=C7NC6=O)N3CC8CC8)C4=C2C=C1)=O