1NM-PP1

Research use only, not for human use.

1NM-PP1(PP1 Analog II) is a cell-permeable PP1 analog that acts as a potent and selective inhibitor of mutant kinases over their wild-type progenitors(IC50=28 uM vSrc; 4.2 nM v-Src-as1 I338G).

1NM-PP1(PP1 Analog II) is a cell-permeable PP1 analog that acts as a potent and selective inhibitor of mutant kinases over their wild-type progenitors(IC50=28 uM vSrc; 4.2 nM v-Src-as1 I338G).

Cdk7 from Cdk7as/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 IC50 of ~50 nM with either substrate. Replacement of wild-type Cdk7 with Cdk7as/as also rendered growth of HCT116 cells sensitive to 1-NM-PP1. In the absence of 1-NM-PP1, the wild-type andCdk7as/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 Cdk7as/as cells 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 the Cdk7as/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 Cdk7as/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.

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PP1 Analog II

Angiogenesis

CDK

CDK7

Cancer

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221244-14-0

331.41

C20H21N5

>98% (HPLC)

DMSO: 10 mM

NC1=C2C(N(C(C)(C)C)N=C2CC3=C4C=CC=CC4=CC=C3)=NC=N1

1-(tert-butyl)-3-(naphthalen-1-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

(-20℃)

With Ice Pack

≥ 2 years