YM458

YM458 is a potent EZH2 and BRD4 dual inhibitor with IC₅₀ s of 490 nM and 34 nM, respectively. YM458 inhibits cell proliferation and colony formation and induces cell cycle arrest and apoptosis in solid cancer cells. YM458 can be used for researching anticancer ^[1].

In Vivo, YM458 (60 mg/kg; IP; every other day, for 38 days) prevents tumor growth with inhibitory rates of 38.6% in AsPC-1 cells and 62.3% in A549 cells^[1]. Pharmacokinetic Parameters of YM458 in Female BALB/c mice^[1]. IP (80 mg/kg) PO (80 mg/kg) t1/2 (h) 3.81 4.16 Tmax (h) 1 1 Cmax (ng/mL) 27126.3 4383.6 AUC0-24 (ng/mL·h) 273220.1 13509.1 CL (mL/min/kg) 4.88 F (%) 4.94

In Vitro, YM458 (compound D7) (0-30 μM; 6 days) has antiproliferative activities against AsPC-1 cells with an IC₅₀ of 0.69 ± 0.16 μM; and (1 μM; 72 hours) significantly decreases the degree of H3K27me3 and c-Myc in AsPC-1^[1]. YM458 (0-30 μM; 4 or 6 days) inhibits cell proliferation on a broad range of solid cancer cells, and significantly suppresses proliferation of A549 lung cancer cells and HCT116 colorectal cancer cells at 1 μM^[1]. YM458 (0.05-0.4 μM; 12-20 days) inhibits colony formation of AsPC-1, HCT116, and A549 cancer cells in a dose-dependent manner^[1].

References:
[1]. Guo Z, et al. Design and Synthesis of Dual EZH2/BRD4 Inhibitors to Target Solid Tumors. J Med Chem. 2022;65(9):6573-6592.