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Catalog No. T2153   CAS 221244-14-0
Synonyms: PP1 Analog II, 1 nM-PP1

1 nM-PP1 is a cell-permeable PP1 analog that acts as a potent and selective inhibitor of mutant kinases over their wild-type progenitors.

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1-NM-PP1, CAS 221244-14-0
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Biological Description
Chemical Properties
Storage & Solubility Information
Description 1 nM-PP1 is a cell-permeable PP1 analog that acts as a potent and selective inhibitor of mutant kinases over their wild-type progenitors.
Targets&IC50 permeable protein kinase D (PKD):0.398 μM
In vitro 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 F91 g 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[1].
Kinase Assay Immunoblotting and immunoprecipitation, and kinase assays of immune complexes, are carried out. To measure Cdk1/cyclin B assembly, extracts (200 μg total protein) from cells in mitosis or G2 are pre-incubated with 2 μM 1-NM-PP1 or DMSO, then added 500 ng purified cyclin B1, amino-terminally tagged with hexahistidine and the Myc epitope, and an ATP-regenerating system. Where indicated, incubations are supplemented with 400 ng purified Csk1 or 600 ng wild-type or analog-sensitive, T-loop-phosphorylated Cdk7/cyclin H/Mat1 complex. After 90 min at room temperature, Myc-cyclin B and associated proteins are immunoprecipitated with anti-Myc antibodies and immune complexes are subjected to immunoblotting, with anti-Myc and anti-Cdk1 antibodies, and tested for histone H1 kinase activity[1].
Cell Research 1-NM-PP1 (1-NMPP1) is dissolved in DMSO and stored, and then diluted with appropriate media before use[1]. Wild-type or Cdk7as/as HCT116 cells are synchronized by incubation in serum-free medium for 48 h and released into medium containing 10% fetal calf serum. Synchronization with thymidine or nocodazole, and analysis of cell-cycle distribution by flow cytometry, are performed. Cell viability is measured by MTT assay[1].
Synonyms PP1 Analog II, 1 nM-PP1
Molecular Weight 331.41
Formula C20H21N5
CAS No. 221244-14-0


Powder: -20°C for 3 years

In solvent: -80°C for 2 years

Solubility Information

DMSO: 27.5 mg/mL

( < 1 mg/ml refers to the product slightly soluble or insoluble )

References and Literature

1. Larochelle S, et al. Requirements for Cdk7 in the assembly of Cdk1/cyclin B and activation of Cdk2 revealed by chemical genetics in human cells. Mol Cell. 2007 Mar 23;25(6):839-50.

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1-NM-PP1 221244-14-0 Angiogenesis Cell Cycle/Checkpoint Metabolism Tyrosine Kinase/Adaptors Src CDK Serine/threonin kinase inhibit Inhibitor 1-NM-PP-1 PP1 Analog II 1 nM-PP1 1NMPP1 1 NM PP1 inhibitor