PHA-767491 hydrochloride
Based on 5 publication(s) in Google Scholar
PHA-767491 hydrochloride is a dual Cdc7/Cdk9 inhibitor, with IC50s of 10 nM and 34 nM, respectively.
For research use only. We do not sell to patients.
- Purity: 99.49%
- CAS No.: 942425-68-5
- Formula: C12H12ClN3O
- Molecular Weight:249.70
-
Storage:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biological Activity
-
Chemical Information
-
Solvent & Solubility
- Protocol
- Purity & Documentation
- References
-
Help & FAQs
-
Bioactive Compound Library Max
HY-L181
-
Bioactive Compound Library
HY-L001
-
Apoptosis Compound Library
HY-L003
-
Cell Cycle/DNA Damage Compound Library
HY-L004
-
Kinase Inhibitor Library
HY-L009
-
Anti-Cancer Compound Library
HY-L025
-
Anti-Aging Compound Library
HY-L034
-
Anti-Breast Cancer Compound Library
HY-L074
-
Anti-Blood Cancer Compound Library
HY-L079
-
Cancer Stem Cells Compound Library
HY-L135
-
Highly Selective Inhibitors Library
HY-L158
-
Highly Selective Activators Library
HY-L159
-
Cell Death Library
HY-L162
-
Serine/Threonine Kinase Inhibitor Library
HY-L164
-
Anti-Hematopathy Compound Library
HY-L171
-
Anti-Ovarian Cancer Compound Library
HY-L173
-
Multi-Target Compound Library
HY-L176
-
MCE Bioactive Compound Library
HY-L001V
-
Protein Kinase Compound Library
HY-L196
-
Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library
HY-L199
-
Cell Proliferation Compound Library
HY-L201
-
High-Throughput Bioactive Compound Library
HY-L205
-
Posttranslational Modification Library
HY-L226
-
High-Efficiency Gene Editing Compound Library
HY-L244
Publications Citing Use of MedChemExpress (MCE) PHA-767491 hydrochloride
More
Biological Activity
|
CDK9 34 nM (IC50) |
CDK2 240 nM (IC50) |
CDK1 250 nM (IC50) |
CDK5 460 nM (IC50) |
GSK3-β 220 nM (IC50) |
Mk2 470 nM (IC50) |
Plk1 980 nM (IC50) |
Chk2 1100 nM (IC50) |
PHA-767491 inhibits proliferation in both cell lines with an IC50 of 0.64 μM in HCC1954 cells and 1.3 μM in Colo-205 cells. PHA-767491 is effective DDK inhibitors in vitro, with IC50 values of 18.6 nM. PHA-767491 (2 μM) completely abolishes Mcm2 phosphorylation by 24 hours in HCC1954 cells[1].
PHA-767491 in combination with 5-FU exhibits much stronger cytotoxicity and induces significant apoptosis manifested by remarkably increased caspase 3 activation and poly(ADP-Ribose) polymerase fragmentation in HCC cells. PHA-767491 directly counteracts the 5-FU-induced phosphorylation of Chk1 and decreases the expression of the anti-apoptotic protein myeloid leukemia cell 1ine[2].
PHA-767491 (0-10 μM) decreases glioblastoma cell viability in a time- and dose-dependent fashion, with IC50 of approximately 2.5 μM for U87-MG and U251-MG cells. PHA-767491 hydrochloride induces apoptosis in glioblastoma cells, suppresses glioblastoma cell proliferation, cell migration and cell invasion[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
-
CAS No. 942425-68-5
-
Appearance Solid
-
Molecular Weight 249.70
-
Formula C12H12ClN3O
-
Color Light yellow to yellow
-
SMILES
O=C1C2=C(NC(C3=CC=NC=C3)=C2)CCN1.[H]Cl
-
Synonyms
CAY-10572 hydrochloride
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Publications (5)
-
Journal Impact Factor
-
Most Recent
-
Autophagy
CDK9 inhibition blocks the initiation of PINK1-PRKN-mediated mitophagy by regulating the SIRT1-FOXO3-BNIP3 axis and enhances the therapeutic effects involving mitochondrial dysfunction in hepatocellular carcinoma. [Abstract]2022 Aug;18(8):1879-1897. PMID: 34890308 -
Nat Commun
CDK9 recruits HUWE1 to degrade RARα and offers therapeutic opportunities for cutaneous T-cell lymphoma. [Abstract]2024 Dec 5;15(1):10594. PMID: 39632829 -
Acta Pharmacol Sin
Novel CDK9 inhibitor oroxylin A promotes wild-type P53 stability and prevents hepatocellular carcinoma progression by disrupting both MDM2 and SIRT1 signaling. [Abstract]2022 Apr;43(4):1033-1045. PMID: 34188177 -
Sci Rep
2021 Mar 8;11(1):5374. PMID: 33686114 -
Genes Genomics
2026 Jun;48(6):817-829. PMID: 41954877
Solvent & Solubility
H2O : 50 mg/mL (200.24 mM; Need ultrasonic)
DMSO : 17.33 mg/mL (69.40 mM; Need ultrasonic and warming; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
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, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
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 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 1 mg/mL (4.00 mM); Clear solution
This protocol yields a clear solution of ≥ 1 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (10.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 1 mg/mL (4.00 mM); Clear solution
This protocol yields a clear solution of ≥ 1 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (10.0 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.
For the following dissolution methods, please prepare the working solution directly:
It is recommended to prepare fresh solutions and use them promptly within a short period of time.
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: PBS
Solubility: 50 mg/mL (200.24 mM); Clear solution; Need ultrasonic
Please enter the basic information of animal experiments:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Working solution concentration: 0.22 mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
Protocol
20 ng of purified human DDK is pre-incubated with increasing concentrations of each DDK inhibitor for 5 min. Then 10 µCi (γ)-32P ATP and 1.5 µM cold ATP are added in a buffer containing 50 mM Tris-HCl (pH 7.5), 10 mM MgCl2, and 1 mM DTT and incubated for 30 min at 30°C. The proteins are denatured in 1X Laemmli buffer at 100°C followed by SDS-PAGE and autoradiography on HyBlot CL film. Auto-phosphorylation of DDK is used as an indicator of its kinase activity. 32P-labeled bands are quantified using ImageJ and the IC50 values are calculated using GraphPad.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
For assays in 96 well plates 2500 cells are plated per well. After 24 hours, cells are treated with small molecule inhibitors and incubated for 72 hours at 37°C. Subsequently the cells are lysed and the ATP content is measured as an indicator of metabolically active cells using the CellTiter-Glo assay. IC50 values are calculated using the GraphPad software. For assays in six well plates, 100,000 cells are plated per well. After 24 hours, cells are treated with small molecule inhibitors and incubated for varying time points. Cells are trypsinized and a suspension is made in 5 mL of phosphate buffered saline. 30 µL of this suspension is mixed with 30 µL of CellTiter-Glo reagent followed by a 10-minute incubation at room temperature. Luminescence is measured using EnVision 2104 Multilabel Reader and BioTek Synergy Neo Microplate Reader.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
-
Data Sheet (280 KB)
-
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)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
-
Handling Instructions (2659 KB)
References
[1]. Sasi NK, et al. The potent Cdc7-Dbf4 (DDK) kinase inhibitor XL413 has limited activity in many cancer cell lines and discovery of potential new DDK inhibitor scaffolds. PLoS One. 2014 Nov 20;9(11):e113300. [Content Brief]
[2]. Li W, et al. Dual Inhibition of Cdc7 and Cdk9 by PHA-767491 Suppresses Hepatocarcinoma Synergistically with 5-Fluorouracil. Curr Cancer Drug Targets. 2015;15(3):196-204. [Content Brief]
[3]. Erbayraktar Z, et al. Cell division cycle 7-kinase inhibitor PHA-767491 hydrochloride suppresses glioblastoma growth and invasiveness. Cancer Cell Int. 2016 Nov 18;16:88. [Content Brief]
[4]. Montagnoli A, et al. A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity. Nat Chem Biol. 2008 Jun;4(6):357-65. [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, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO / H2O | 1 mM | 4.0048 mL | 20.0240 mL | 40.0481 mL | 100.1201 mL |
| 5 mM | 0.8010 mL | 4.0048 mL | 8.0096 mL | 20.0240 mL | |
| 10 mM | 0.4005 mL | 2.0024 mL | 4.0048 mL | 10.0120 mL | |
| 15 mM | 0.2670 mL | 1.3349 mL | 2.6699 mL | 6.6747 mL | |
| 20 mM | 0.2002 mL | 1.0012 mL | 2.0024 mL | 5.0060 mL | |
| 25 mM | 0.1602 mL | 0.8010 mL | 1.6019 mL | 4.0048 mL | |
| 30 mM | 0.1335 mL | 0.6675 mL | 1.3349 mL | 3.3373 mL | |
| 40 mM | 0.1001 mL | 0.5006 mL | 1.0012 mL | 2.5030 mL | |
| 50 mM | 0.0801 mL | 0.4005 mL | 0.8010 mL | 2.0024 mL | |
| 60 mM | 0.0667 mL | 0.3337 mL | 0.6675 mL | 1.6687 mL | |
| H2O | 80 mM | 0.0501 mL | 0.2503 mL | 0.5006 mL | 1.2515 mL |
| 100 mM | 0.0400 mL | 0.2002 mL | 0.4005 mL | 1.0012 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
PHA-767491 hydrochloride Related Classifications
HY-13461A Related Classifications
Powered by Bioz