YM281

YM281 is a potent EZH2 inhibitor. YM281 induces cell apoptosis and cell cycle arrest at the G0/G1 phase. YM281 shows antitumor effects in vivo. YM281 has the potential for the research of lymphoma[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Histone Methyltransferase

YM281 (compound V2) (0-6 µM; 0-48 h) decreases the EZH2 protein level and the PRC2 (polycomb repressive complex 2) complex through the VHL (vonHippel−Lindau)-dependent ubiquitin-proteasome system[1]. YM281 (0-10 µM; 24 h) shows anticancer effects in lymphoma cells[1]. YM281 (0-5 µM) induces cell apoptosis and cell cycle arrest at the G0/G1 phase[1]. YM281 (0-5 µM; 24 h) increases the activity of caspase-3 and -7 and meanwhile reduces the cell viability in primary lymphoma cells[1]. Western Blot Analysis[1] Cell Line: SU-DHL-2, 22Rv1 cells Concentration: 0-6 µM Incubation Time: 0-48 h Result: Abrogated both the EZH2 protein level and the H3K27me3 degree in a concentration-dependent manner in 24 h, had no significant effect on the protein level of EZH1,and significantly increased the expression of EZH2 ubiquitination. Cell Viability Assay[1] Cell Line: SU-DHL-2, SU-DHL-4, SU-DHL-6 cells Concentration: 0-10 µM Incubation Time: 24 h Result: Induced nearly complete cell viability inhibition. Cell Cycle Analysis[1] Cell Line: SU-DHL-6 cells Concentration: 1, 3, 5 µM Incubation Time: 24 h Result: Induced cell cycle arrest at the G0/G1 phase and a profound sub-G1 population increasein a concentration-dependent manner. Apoptosis Analysis[1] Cell Line: SU-DHL-6 cells Concentration: 0-5 µM Incubation Time: 48 h Result: Significantly increased the expression of cleaved caspase-3 and PARP.

YM281 (80, 100 mg/kg; i.v.; 6 times for 3 weeks) shows antitumor effects and significantly reduces the expression of EZH2 protein and H3K27me3 levels[1]. Animal Model: Balb/c nude mice (SU-DHL-6 xenograft model)[1] Dosage: 80 mg/kg Administration: I.v.; 6 times for 3 weeks Result: Remarkably suppressed the tumor volume and significantly reduced the EZH2 protein and H3K27me3 levels. Animal Model: Balb/c nude mice (Jeko-1 xenograft model)[1] Dosage: 100 mg/kg Administration: I.v.; 6 times for 3 weeks Result: Shows anti-tumor effects with the significantly reduced the expression of EZH2 protein and H3K27me3 levels.

[1]. Tu Y,et al. Design, Synthesis, and Evaluation of VHL-Based EZH2 Degraders to Enhance Therapeutic Activity against Lymphoma. J Med Chem. 2021 Jul 22;64(14):10167-10184.