4-氨基1-叔丁基-3-(1-萘甲基)吡唑并[3,4-D]嘧啶
中文名称:
4-氨基1-叔丁基-3-(1-萘甲基)吡唑并[3,4-D]嘧啶
中文同义词:
4-氨基1-叔丁基-3-(1-萘甲基)吡唑并[3,4-D]嘧啶;突变型CDK7抑制剂(1-NM-PP1)
英文名称:
1 NM-PP1
英文同义词:
4-AMINO-1-TERT-BUTYL-3-(1-NAPHTHYLMETHYL)PYRAZOLO[3,4-D]PYRIMIDINE;4-AMINO-1-TERT-BUYTL-3-(1-NAPHTHYLMETHYL)PYRAZOLO[3,4-D]PYRIMIDINE;1 NM-PP1;MUTANT KINASES INHIBITOR II;PP1 ANALOG II;1-(1,1-Dimethylethyl)-3-(1-naphthalenylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine;1-tert-Butyl-3-(naphthalen-1-ylmethyl)-1H-pyrazolo[3,4-D]pyrimidin-4-amine;Chebi:52309
CAS号:
221244-14-0
分子式:
C20H21N5
分子量:
331.41
EINECS号:
相关类别:
细胞生物学试剂;小分子抑制剂，天然产物;小分子抑制剂;Inhibitors;Bases Related Reagents;Intermediates Fine Chemicals;Nucleotides;Pharmaceuticals;Tyrosine Kinase Inhibitors;API
Mol文件:
221244-14-0.mol
熔点
175-176°C
沸点
545.7±45.0 °C(Predicted)
密度
1.25±0.1 g/cm3(Predicted)
储存条件
Keep in dark place,Sealed in dry,Store in freezer, under -20°C
形态
White solid
酸度系数(pKa)
4.50±0.30(Predicted)
生物活性
1-NM-PP1，细胞渗透性 PP1 类似物，是一种有效的 Src 家族激酶抑制剂，对 v-Src-as1 与 c-Fyn-as1 的 IC50 值分别为 4.3 nM、3.2 nM。
靶点
IC50: 4.3 nM (v-Src-as1), 3.2 nM (c-Fyn-as1), 28 μM (v-Src), 1 μM (c-Fyn), 3.4 μM (c-Abl), 29 μM (CDK2), 24 μM (CAMKII), 120 nM (cAbl-as2), 5 nM (CDK2-as1), 8 nM (CAMKII-as1)
体外研究
Cdk7 from Cdk7 as/as or Cdk7 +/+ 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 IC 50 of ~50 nM with either substrate. Replacement of wild-type Cdk7 with Cdk7 as/as also rendered growth of HCT116 cells sensitive to 1-NM-PP1. In the absence of 1-NM-PP1, the wild-type and Cdk7 as/as cells 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 homozygous Cdk7 as/as cells are sensitive to 1-NM-PP1, however, with an IC 50 ~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 the Cdk7 as/as cells, 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 of Cdk7 as/as cells 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.
