PHA-793887

Catalog No.S1487 Batch:S148701

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Technical Data

Formula

C19H31N5O2
Molecular Weight 361.48 CAS No. 718630-59-2
Solubility (25°C)* In vitro DMSO 72 mg/mL (199.18 mM)
Ethanol 72 mg/mL (199.18 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
30%propylene glycol 5%Tween80 65%D5W
15.0mg/ml Taking the 1 mL working solution as an example, add 300 μL of 50 mg/ml clarified propylene glycol stock solution to 50 μL of Tween 80, mix evenly to clarify it; then continue to add 650 μL of D5W to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description PHA-793887 is a novel and potent inhibitor of CDK2, CDK5 and CDK7 with IC50 of 8 nM, 5 nM and 10 nM. It is greater than 6-fold more selective for CDK2, 5, and 7 than CDK1, 4, and 9. PHA-793887 induces cell-cycle arrest and apoptosis. Phase 1.
Targets
CDK5/p25 [1]
(Cell-free assay)		 CDK2/CyclinA [1]
(Cell-free assay)		 CDK2/CyclinE [1]
(Cell-free assay)		 CDK7/CyclinH [1]
(Cell-free assay)		 CDK1/CyclinB [1]
(Cell-free assay)		 View More
5 nM 8 nM 8 nM 10 nM 60 nM
In vitro PHA-793887 has low activity against CDK1, CDK4, CDK9 and GSK3β with IC50 of 60 nM, 62 nM, 138 nM and 79 nM, respectively. PHA-793887 inhibits cell proliferation of many tumor cell lines, including A2780, HCT-116, COLO-205, C-433, DU-145, A375, PC3, MCF-7, and BX-PC3, with IC50 of 88 nM–3.4 μM. PHA-793887 (1 μM) shows a decrease in the S phase, a subsequent increase of the G1 phase and a slight accumulation of G2/M phase in A2780 cells. PHA-793887 (3 μM) significantly increases G2/M phase and reduces DNA synthsis. [1] PHA-793887 is cytotoxic for leukemic cell lines, including K562, KU812, KCL22, and TOM1, with IC50 of 0.3–7 μM, but it is not cytotoxic for normal unstimulated peripheral blood mononuclear cells or CD34+ hematopoietic stem cells. In colony assays, PHA-793887 shows very high activity against leukemia cell lines with IC50 less than 0.1 μM. PHA-793887 induces cell-cycle arrest, inhibits Rb and nucleophosmin phosphorylation, and modulates cyclin E and cdc6 expression at 0.2−1 μM and induces apoptosis at 5 μM. [2]
In vivo PHA-793887 (10–30 mg/kg) shows good efficacy in the human ovarian A2780, colon HCT-116, and pancreatic BX-PC3 carcinoma xenograft models. [1] PHA-793887 (20 mg/kg) is effective in xenograft models of K562 and HL60 cells, primary leukemic disseminated model, and a high-burden disseminated ALL-2 model derived from a relapsed Philadelphia-positive acute lymphoid leukemia patient. [2]
Features Multi-CDK inhibitor.

Protocol (from reference)

Kinase Assay:[3]
  • CDK Kinase Assay

    The biochemical activity of compounds is determined by incubation with specific enzymes and substrates, followed by quantitation of the phosphorylated product. PHA-793887 (1.5 nM–10 μM) is incubated for 30−90 min at room temperature in the presence of ATP/33P-γ-ATP mix, substrate, and the specific enzyme (0.7−100 nM) in a final volume of 30 μL of kinase buffer, using 96 U bottom plates. After incubation, the reaction is stopped and the phosphorylated substrate is separated from nonincorporated radioactive ATP using SPA beads, Dowex resin, or Multiscreen phosphocellulose filter as follows: (1) For SPA Assays. The reaction is stopped by the addition of 100 μL of PBS + 32 mM EDTA + 0.1% Triton X-100 + 500 μM ATP, containing 1 mg of streptavidin-coated SPA beads. After 20 min of incubation for substrate capture, 100 μL of the reaction mixture is transferred into Optiplate 96-well plates containing 100 μL of 5 M CsCl, left to stand for 4 hours to allow stratification of beads to the top of the plate, and counted using TopCount to measure substrate-incorporated phosphate. (2) For Dowex Resin Assay. An amount of 150 μL of resin/formate, pH 3.00, is added to stop the reaction and capture unreacted 33P-γ-ATP, separating it from the phosphorylated substrate in solution. After 60 min of rest, 50 μL of supernatant is transferred to Optiplate 96-well plates. After the additon of 150 μL of Microscint 40, the radioactivity is counted in the TopCount. (3) For Multiscreen Assay. The reaction is stopped with the addition of 10 μL of EDTA (150 mM). An amount of 100 μL is transferred to a MultiScreen plate to allow substrate binding to phosphocellulose filter. Plates are then washed three times with 100 μL of H2PO4 (75 mM) filtered by a MultiScreen filtration system, and dried. After the additon of 100 μL of Microscint 0, radioactivity is counted in the TopCount. IC50 values are obtained by nonlinear regression analysis.

Cell Assay:[1]
  • Cell lines

    A2780 cells

  • Concentrations

    0.1 nM-1 μM, dissolved in DMSO

  • Incubation Time

    72 hours

  • Method

    Cells are seeded into 96- or 384-wells plates at final concentration ranging from 1 × 104 to 3 × 104 per cm2. After 24 hours, cells are treated using serial dilution of PHA-793887. At 72 hours after the treatment, the amount of cells are evaluated using the CellTiter-Glo assay. IC50 values are calculated using a sygmoidal fitt
Animal Study:[1]
  • Animal Models

    Mouse xenograft models of human ovarian A2780, colon HCT-116 and pancreatic BX-PC3 carcinoma

  • Dosages

    10, 20, and 30 mg/kg

  • Administration

    Intravenous injection once daily

Customer Product Validation

Data from [Data independently produced by Mol Cancer Ther, 2014, 13(3), 662-74]

,

Data from [Data independently produced by , , Acta Pharmacol Sin, 2017, 38(8):1104-1119]

Selleck's PHA-793887 has been cited by 15 publications

Identification and subsequent validation of transcriptomic signature associated with metabolic status in endometrial cancer [ Sci Rep, 2023, 13(1):13763] PubMed: 37612452
Identification and subsequent validation of transcriptomic signature associated with metabolic status in endometrial cancer [ Sci Rep, 2023, 13(1):13763] PubMed: 37612452
Sigma non-opioid receptor 1 is a potential therapeutic target for long QT syndrome [ Nat Cardiovasc Res, 2022, 1(2):142-156] PubMed: 36051854
Predicting heterogeneity in clone-specific therapeutic vulnerabilities using single-cell transcriptomic signatures [ Genome Med, 2021, 13(1):189] PubMed: 34915921
The Global Phosphorylation Landscape of SARS-CoV-2 Infection [ Cell, 2020, 182(3):685-712.e19] PubMed: 32645325
The Global Phosphorylation Landscape of SARS-CoV-2 Infection [ Cell, 2020, 182(3):685-712.e19] PubMed: 32645325
Dynamic Phosphorylation and Dephosphorylation of Cyclase-Associated Protein 1 by Antagonistic Signaling through Cyclin-Dependent Kinase 5 and cAMP Are Critical for the Protein Functions in Actin Filament Disassembly and Cell Adhesion. [ Mol Cell Biol, 2020, 40(4)] PubMed: 31791978
The TRAPP complex mediates secretion arrest induced by stress granule assembly. [ EMBO J, 2019, 38(19):e101704] PubMed: 31429971
Cell cycle-dependent phosphorylation of PRPS1 fuels nucleotide synthesis and promotes tumorigenesis [ Cancer Res, 2019, 10.1158/0008-5472.CAN-18-2486] PubMed: 31253668
MultiBacMam Bimolecular Fluorescence Complementation (BiFC) tool-kit identifies new small-molecule inhibitors of the CDK5-p25 protein-protein interaction (PPI) [ Sci Rep, 2018, 8(1):5083] PubMed: 29572554

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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