| Identification | Back Directory | [Name]
INDEX NAME NOT YET ASSIGNED | [CAS]
2770108-93-3 | [Synonyms]
6H-Thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide, 4-(4-chlorophenyl)-N-[5-[[3′-[[[(1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]amino]carbonyl]-5′-[ethyl(tetrahydro-2H-pyran-4-yl)amino]-4′-methyl[1,1′-biphenyl]-4-yl]oxy]pentyl]-2,3,9-trimethyl-, (6S)- | [Molecular Formula]
C53H61ClN8O5S | [MOL File]
2770108-93-3.mol | [Molecular Weight]
957.62 |
| Hazard Information | Back Directory | [Uses]
YM458 is a potent EZH2 and BRD4 dual inhibitor with IC50s 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 |
| Animal Model: | BALB/c nude mice (injected with A549 or AsPC-1)[1] | | Dosage: | 60 mg/kg | | Administration: | IP; every other day, for 38 days | | Result: | Prevented tumor growth with inhibitory rates of 38.6% in AsPC-1 cells and 62.3% in A549 cells. |
| [IC 50]
EZH2; EZH2: 490 nM (IC50); BRD4: 34 nM (IC50) | [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. DOI:10.1021/acs.jmedchem.1c01876 |
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