|Product Name||CH5183284||CAS No.||1265229-25-1|
|Molecular Weight||356.38||Molecular Formula||C20H16N6O|
CH5183284 is a selective and orally available FGFR1/2/3 inhibitor. The IC50 values of CH5183284 on the enzyme activity of FGFR1/2/3/4 were 9.3, 7.6, 22, and 290 nM, respectively. IC50 value: 9.3, 7.6, 22, and 290 nM (FGFR1/2/3/4) Target: FGFR in vitro: The binding affinity (Kd) of CH5183284 for FGFR1, FGFR2, FGFR3, FGFR4, and KDR was 20, 20, 25, 740, and 960 nM, respectively (using the DiscoveRx panel). CH5183284 selectively inhibits FGFR1, FGFR2, and FGFR3 but does not inhibit kinase insert domain receptor (KDR) or other kinases.  CH5183284 shows antiproliferative activity against FGFR3-BAIAP2L1-positive cells only, including the bladder cancer cell line SW780, Rat-2_F3-B cells, and NIH-3T3 cells expressing FGFR3-BAIAP2L1, but not against NIH-3T3 cells expressing EML4-ALK (3T3_EML4-ALK) or HT1376 cells harboring WT FGFR. CH5183284/Debio 1347 induces apoptosis in SW780 and Rat-2_F3-B cells and suppresses FRS and ERK phosphorylation.  in vivo: CH5183284 shows significant antitumor activity against xenografts with FGFR genetic alterations. CH5183284 suppresses p-FGFR for at least 7 hours in SNU-16 xenograft tissue, as well as the downstream signaling, as indicated by a reduction in p-FRS, p-ERK, and p-S6.  CH5183284/Debio 1347 shows antitumor activity in SW780 and Rat-2_F3-B xenograft models, but not in WT FGFR HT1376 xenograft tumors. The downstream signals are suppressed in Rat-2_F3-B xenograft tumors treated by CH5183284/Debio 1347.