PHA-793887
Based on 4 publication(s) in Google Scholar
PHA-793887 is a potent, ATP-competitive CDK inhibitor, can inhibit Cdk2, Cdk1, Cdk4, and Cdk9 with IC50s of 8 nM, 60 nM, 62 nM and 138 nM, respectively, and also inhibits glycogen synthase kinase 3β with an IC50 of 79 nM.
For research use only. We do not sell to patients.
- Purity: 99.25%
- CAS No.: 718630-59-2
- Formula: C19H31N5O2
- Molecular Weight:361.48
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) PHA-793887
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Biological Activity
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Cdk5/p25 5 nM (IC50) |
cdk2/cyclin A 8 nM (IC50) |
CDK2/cyclinE 8 nM (IC50) |
CDK7/cyclin H 10 nM (IC50) |
Cdk1/cyclin B 60 nM (IC50) |
Cdk4/cyclin D1 62 nM (IC50) |
CDK9/cyclinT1 138 nM (IC50) |
GSK-3β 79 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A2780 | IC50 |
0.09 μM
Compound: 31
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Antiproliferative activity against human A2780 cells after 72 hrs by fluorescence assay
Antiproliferative activity against human A2780 cells after 72 hrs by fluorescence assay
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[PMID: 20153204] |
| A-375 | IC50 |
0.396 μM
Compound: 31
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Antiproliferative activity against human A375 cells after 72 hrs by SRB assay
Antiproliferative activity against human A375 cells after 72 hrs by SRB assay
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[PMID: 20153204] |
| BXPC-3 | IC50 |
3.444 μM
Compound: 31
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Antiproliferative activity against human BxPC3 cells after 72 hrs by SRB assay
Antiproliferative activity against human BxPC3 cells after 72 hrs by SRB assay
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[PMID: 20153204] |
| COLO 205 | IC50 |
0.188 μM
Compound: 31
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Antiproliferative activity against human COLO205 cells after 72 hrs by SRB assay
Antiproliferative activity against human COLO205 cells after 72 hrs by SRB assay
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[PMID: 20153204] |
| DU-145 | IC50 |
0.303 μM
Compound: 31
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Antiproliferative activity against human DU145 cells after 72 hrs by SRB assay
Antiproliferative activity against human DU145 cells after 72 hrs by SRB assay
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[PMID: 20153204] |
| HCT-116 | IC50 |
0.163 μM
Compound: 31
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Antiproliferative activity against human HCT116 cells after 72 hrs by SRB assay
Antiproliferative activity against human HCT116 cells after 72 hrs by SRB assay
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[PMID: 20153204] |
| MCF7 | IC50 |
1.284 μM
Compound: 31
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Antiproliferative activity against human MCF7 cells after 72 hrs by SRB assay
Antiproliferative activity against human MCF7 cells after 72 hrs by SRB assay
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[PMID: 20153204] |
| PC-3 | IC50 |
0.601 μM
Compound: 31
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Antiproliferative activity against human PC3 cells after 72 hrs by SRB assay
Antiproliferative activity against human PC3 cells after 72 hrs by SRB assay
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[PMID: 20153204] |
PHA-793887 partially inhibits Rb phosphorylation at 1 μM and almost completely at 3 μM, in A2780 tumor cell line. PHA-793887 (1 μM) partially inhibits phosphorylation of the Cdk2 substrates Rb and NPM in A2780 tumor cell line. PHA-793887 (6 μM) significantly inhibits Rb and NPM phosphorylation in MCF7 cell line[1]. PHA-793887 shows cytotoxic activities against leukemic cell lines in vitro, with IC50 ranging from 0.3 to 7 μM. In colony assays, PHA-793887 is highly cytotoxic for leukemia cell lines, with an IC50 <0.1 μM. PHA-793887 induces cell-cycle arrest, inhibits Rb and nucleophosmin phosphorylation, and modulates cyclin E and cdc6 expression at low doses of 0.2 to 1 μM and induces apoptosis at the highest dose of 5 μM. PHA-793887 is a novel inhibitor of several cdk, including cdk1, cdk2, cdk4, cdk5, cdk7, and cdk9 with IC50 in the 5 to 140 nM range[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 718630-59-2
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Appearance Solid
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Molecular Weight 361.48
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Formula C19H31N5O2
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Color White to yellow
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SMILES
CC(C)CC(NC1=NNC2=C1CN(C(C3CCN(C)CC3)=O)C2(C)C)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (4)
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Journal Impact Factor
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Most Recent
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Sci Transl Med
PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]2018 Jul 18;10(450):eaaq1093. PMID: 30021885 -
Sci Data
High-throughput drug screening identifies novel therapeutics for Low Grade Serous Ovarian Carcinoma. [Abstract]2024 Sep 19;11(1):1024. PMID: 39300112 -
Bioinform Biol Insights
Integrative Analysis for Identification of Therapeutic Targets and Prognostic Signatures in Non-Small Cell Lung Cancer. [Abstract]2022 Apr 6;16:11779322221088796. PMID: 35422618 -
Solvent & Solubility
DMSO : ≥ 50 mg/mL (138.32 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (6.92 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
Cytotoxicity assays are performed using the Alamar blue vital dye. For each cell line, preliminary dose−response curves are performed to establish the cell-concentration range, giving a linear relationship with fluorescence. For cell lines, 5,000 to 20,000 cells are plated in 200 μL complete medium in 96-well plates, in the presence or absence of increasing doses of drugs (0.01−10 μM). For ALL-2 and AML-PS leukemias 10 × 105 cells/well are plated in StemSpanSFEM medium and treated with the same range of drug concentrations. Peripheral blood mononuclear cells and cord blood CD34+ cells are plated 1 × 105 cells/well in presence or absence of 1 μg/mL phytohemagglutin or growth factor cocktail (50 ng/mL stem cell factor, 20 ng/mL each of granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, interleukin-3, interleukin-6, and 3 U/mL erythropoietin), respectively. In all cases, after 48 hours culture, 1/10 volume Alamar blue solution is added and incubated overnight. The plates are then read in a fluorimeter with excitation at 535 nm and emission at 590 nm. Cytotoxicity is calculated as percentage of fluorescence with respect to untreated control, after subtracting for background fluorescence in absence of cells.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
107 HL60 and K562 cells are inoculated subcutaneously in SCID mice. Animals are randomized in seven mice per group. PHA-793887 is administered at 20 mg/kg intravenous (IV) once a day, continuously for 10 days (from day 9 to day 18) in HL60 model and with a two 5-day cycles (from day 9 to day 13 and from day 17 to day 21) in K562-bearing mice. Glivec is orally administered for 9 consecutive days from day 9 onward in the K562 xenograft model. Tumor growth and net body weight are evaluated twice a week. The tumor weight is calculated according to the following formula: tumor weight = length (mm) × width2 (mm) /2. The effect of the anticancer treatment is determined as the delay in onset of an exponential growth of tumors. This delay (T − C value) is defined as the difference of median time (in days) required for the tumors of treatment (T) and control groups (C) to reach a predetermined size. Toxicity is evaluated on the basis of the body weight reduction.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (287 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[1]. Locatelli G, et al. Transcriptional analysis of an E2F gene signature as a biomarker of activity of the cyclin-dependent kinase inhibitor PHA-793887 in tumor and skin biopsies from a phase I clinical study. Mol Cancer Ther. 2010 May;9(5):1265-73. [Content Brief]
[2]. Massard C, et al. A first in man, phase I dose-escalation study of PHA-793887, an inhibitor of multiple cyclin-dependent kinases (CDK2, 1 and 4) reveals unexpected hepatotoxicity in patients with solid tumors. Cell Cycle. 2011 Mar 15;10(6):963-70. Epub 2011 Mar 15. [Content Brief]
[3]. Alzani R, et al. Therapeutic efficacy of the pan-cdk inhibitor PHA-793887 in vitro and in vivo in engraftment and high-burden leukemia models. Exp Hematol. 2010 Apr;38(4):259-269.e2. [Content Brief]
[4]. Brasca MG, et al. Optimization of 6,6-dimethyl pyrrolo[3,4-c]pyrazoles: Identification of PHA-793887, a potent CDK inhibitor suitable for intravenous dosing. Bioorg Med Chem. 2010 Mar 1;18(5):1844-53. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.7664 mL | 13.8320 mL | 27.6640 mL | 69.1601 mL |
| 5 mM | 0.5533 mL | 2.7664 mL | 5.5328 mL | 13.8320 mL | |
| 10 mM | 0.2766 mL | 1.3832 mL | 2.7664 mL | 6.9160 mL | |
| 15 mM | 0.1844 mL | 0.9221 mL | 1.8443 mL | 4.6107 mL | |
| 20 mM | 0.1383 mL | 0.6916 mL | 1.3832 mL | 3.4580 mL | |
| 25 mM | 0.1107 mL | 0.5533 mL | 1.1066 mL | 2.7664 mL | |
| 30 mM | 0.0922 mL | 0.4611 mL | 0.9221 mL | 2.3053 mL | |
| 40 mM | 0.0692 mL | 0.3458 mL | 0.6916 mL | 1.7290 mL | |
| 50 mM | 0.0553 mL | 0.2766 mL | 0.5533 mL | 1.3832 mL | |
| 60 mM | 0.0461 mL | 0.2305 mL | 0.4611 mL | 1.1527 mL | |
| 80 mM | 0.0346 mL | 0.1729 mL | 0.3458 mL | 0.8645 mL | |
| 100 mM | 0.0277 mL | 0.1383 mL | 0.2766 mL | 0.6916 mL |
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