"目录号: HY-13942
1-NM-PP1 抑制突变型Cdk7，IC50约为 50 nM。
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生物活性
Description
1-NM-PP1 inhibitsCdk7recovered from the mutant, but not the wild-type cells with an IC50of ~50 nM with either substrate.
IC50& Target
CDK7[1]
In Vitro
Cdk7 fromCdk7as/asorCdk7+/+cells is immunoprecipitated and tested its kinase activity towards both a Pol II CTD-containing fusion protein (GST-CTD) and human Cdk2. Cdk7 recovered from the mutant, but not the wild-type, cells is inhibited by 1-NM-PP1 (1-NMPP1), with an IC50of ~50 nM with either substrate. Replacement of wild-type Cdk7 withCdk7as/asalso rendered growth of HCT116 cells sensitive to 1-NM-PP1. In the absence of 1-NM-PP1, the wild-type andCdk7as/ascells had population doubling times of ~17.9 and ~20.2 h, respectively, with similar cell-cycle distributions in asynchronous culture, indicating minimal impairment of Cdk7 function by the F91G mutation per se. The homozygousCdk7as/ascells are sensitive to 1-NM-PP1, however, with an IC50~100 nM measured by cell viability (MTT) assays performed after 96 h of 1-NM-PP1 exposure. In contrast, wild-type HCT116 cells are resistant to 10 μM 1-NM-PP1. Addition of 10 μM 1-NM-PP1 retards G1/S progression by the mutant but not the wild-type cells. When added simultaneously with serum to theCdk7as/ascells, 1-NM-PP1 prevents any progression into S phase in the next 15 h. After 24 h, there is evidence of progression into S-phase by a fraction ofCdk7as/ascells released from serum starvation directly into medium containing 1-NM-PP1, while a fraction remained in G1. The addition of 1-NM-PP1 3 h or 6 h after serum addition delays S-phase entry by ~7 h or by ~3 h, respectively[1].
References
