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描述 | Mutations in the CBP/EP300 bromodomain are linked to the onset of neurological disorders and lymphomas. CPI-637 is a selective and cell-active CBP/EP300 bromodomain inhibitor with IC50 values of 0.03±0.01, 0.051±0.004, 11.0±0.6μM for CBP, EP300, and BRD4 BD-1, respectively. The EC50 value of CPI-637 for CBP is 0.3±0.1μM. CPI-637 inhibited the expression of MYC, a transcription factor in human cancers, with an EC50 value of 0.60μM[2]. In mice inoculated with Q165P-mutant prostate cancer cells, combined treatment with CPI-637 (30mg/kg) and JQ1 (50mg/kg) five days a week for three consecutive weeks significantly reduced tumor volume and suppressed the phosphorylation of AKT, the expression of androgen receptor and its downstream target genes[3]. | ||
作用机制 | CPI-637 is a selective benzodiazepinone CBP/EP300 bromodomain inhibitor. The benzodiazepinone core of CPI-637 recapitulated the key hydrogen bonding interactions with the indazole substituents filling space above Pro1110 and the Pro/Arg cleft[2]. |
实验方案 | |||
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1mg | 5mg | 10mg | |
1 mM 5 mM 10 mM |
2.59mL 0.52mL 0.26mL |
12.94mL 2.59mL 1.29mL |
25.88mL 5.18mL 2.59mL |
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