| Identification | Back Directory | [Name]
Benzamide, 4-[[(4R)-5-(cyclohexylmethyl)-4-ethyl-4,5-dihydro-1-methyl[1,2,4]triazolo[4,3-f]pteridin-7-yl]amino]-3-methoxy-N-(1-methyl-4-piperidinyl)- | [CAS]
2412707-81-2 | [Synonyms]
PLK1/BRD4-IN-1
Benzamide, 4-[[(4R)-5-(cyclohexylmethyl)-4-ethyl-4,5-dihydro-1-methyl[1,2,4]triazolo[4,3-f]pteridin-7-yl]amino]-3-methoxy-N-(1-methyl-4-piperidinyl)- | [Molecular Formula]
C31H43N9O2 | [MOL File]
2412707-81-2.mol | [Molecular Weight]
573.73 |
| Hazard Information | Back Directory | [Uses]
WNY0824 (PLK1/BRD4-IN-1) is an orally active dual inhibitor of PLK1 and BET protein families, with IC50 values ??of 22, 402.5, 150.7, 103.9, and 311.9 nmol/L for PLK1, BRD2, BRD3, BRD4, and BRDT, respectively. WNY0824 induces cell cycle arrest and apoptosis by inhibiting AR- and MYC-mediated transcriptional processes. In addition, WNY0824 also inhibits tumor growth in Enzalutamide (HY-70002) resistant CRPC xenograft tumor models[1][2]. | [in vivo]
| Animal Model: | Five weeks old male NOD-SCID mice[1]. | | Dosage: | 60 mg/kg/d | | Administration: | Oral gavage, 18 days; tumor xenograft models were established by subcutaneously injecting 100 μL of 1×108 cell/mL MV4-11 cell suspension into NOD-SCID mice. | | Result: | Resulted in a significant decrease in average tumor size, with 66% tumor growth inhibition, and didn’t obviously affect the body weight of mice. |
| [IC 50]
PLK1: 22 nM (IC50); BRD2: 402.5 nM (IC50); BRD3: 150.7 nM (IC50); BRD4: 103.9 nM (IC50); BRDT: 311.9 nM (IC50) | [References]
[1] Ning-Yu Wang, et al. Design, synthesis, and biological evaluation of 4,5-dihydro-[1,2,4]triazolo[4,3-f]pteridine derivatives as novel dual-PLK1/BRD4 inhibitors. Eur J Med Chem. 2020 Apr 1;191:112152. DOI:10.1016/j.ejmech.2020.112152
[2] Ying Xu, et al. "Novel dual BET and PLK1 inhibitor WNY0824 exerts potent antitumor effects in CRPC by inhibiting transcription factor function and inducing mitotic abnormality." Molecular Cancer Therapeutics 19.6 (2020): 1221-1231. DOI:10.1158/1535-7163.MCT-19-0578 |
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