Home Cell Cycle CDK inhibitor - Apoptosis related activator PHA-793887 For research use only.

PHA-793887

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.

PHA-793887 Chemical Structure

PHA-793887 Chemical Structure

CAS No. 718630-59-2

Purity & Quality Control

Batch: S148701 DMSO]72 mg/mL]false]Ethanol]72 mg/mL]false]Water]Insoluble]false Purity: 99.64%
99.64

PHA-793887 Related Products

Signaling Pathway

CDK Signaling Pathways

CDK Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human A2780 cells Proliferation assay 72 h Antiproliferative activity against human A2780 cells after 72 hrs by fluorescence assay, IC50=0.09 μM 20153204
human HCT116 cells Proliferation assay 72 h Antiproliferative activity against human HCT116 cells after 72 hrs by SRB assay, IC50=0.163 μM 20153204
human COLO205 cells Proliferation assay 72 h Antiproliferative activity against human COLO205 cells after 72 hrs by SRB assay, IC50=0.188 μM 20153204
human C-433 cells Proliferation assay 72 h Antiproliferative activity against human C-433 cells after 72 hrs by SRB assay, IC50=0.285 μM 20153204
human DU145 cells Proliferation assay 72 h Antiproliferative activity against human DU145 cells after 72 hrs by SRB assay, IC50=0.303 μM 20153204
human A375 cells Proliferation assay 72 h Antiproliferative activity against human A375 cells after 72 hrs by SRB assay, IC50=0.396 μM 20153204
human PC3 cells Proliferation assay 72 h Antiproliferative activity against human PC3 cells after 72 hrs by SRB assay, IC50=0.601 μM 20153204
human MCF7 cells Proliferation assay 72 h Antiproliferative activity against human MCF7 cells after 72 hrs by SRB assay, IC50=1.284 μM 20153204
human BxPC3 cells Proliferation assay 72 h Antiproliferative activity against human BxPC3 cells after 72 hrs by SRB assay, IC50=3.444 μM 20153204
human A2780 cells Function assay 3 μM Inhibition of CDK in human A2780 cells assessed as accumulation of hypophosphorylated form of retinoblastoma protein at 3 uM by immunohistochemistry 20153204
Click to View More Cell Line Experimental Data

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.
Features Multi-CDK inhibitor.
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)		 Click to View More Targets
5 nM 8 nM 8 nM 10 nM 60 nM
In vitro
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]
Kinase Assay 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 Research 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
In Vivo
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]
Animal Research 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

Chemical Information & Solubility

Molecular Weight 361.48 Formula

C19H31N5O2
CAS No. 718630-59-2 SDF Download PHA-793887 SDF
Smiles CC(C)CC(=O)NC1=NNC2=C1CN(C2(C)C)C(=O)C3CCN(CC3)C
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 72 mg/mL ( (199.18 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 72 mg/mL

Water : Insoluble


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