PHA-767491

SKU: orb1300981

Description

PHA-767491 is a potent, ATP-competitive dual inhibitor of Cdc7 and CDK9 kinases, exhibiting IC50 values of 10 nM and 34 nM, respectively. It is widely used in biochemical and cellular research to investigate DNA replication stress, transcription, and oncology-related pathways in both in vitro and in vivo models.

Research Area

Metabolism Research

Key Properties

• CAS Number: 845714-00-3
• MW: 213.24
• Purity: >99.99% (May vary between batches)
• Formula: C₁₂H₁₁N₃O
• SMILES: O=C1C=2C=C(NC2CCN1)C=3C=CN=CC3
• Target: Cholecystokinin Receptor,CDK,GSK-3
• Solubility: DMSO:40 mg/mL (187.58 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  Chk2:1100 nM|CDK1:250 nM|CDK5:460 nM|MK2:470 nM|CDC7:10 nM|GSK-3β:220 nM|PLK1:980 nM|CDK9:34 nM|CDK2:240 nM
• In Vivo:
  PHA-767491 inhibits cell proliferation in two cell lines, achieving IC50 values of 0.64 μM in HCC1954 cells and 1.3 μM in Colo-205 cells. Additionally, PHA-767491 (2 μM) completely abolishes Mcm2 phosphorylation in HCC1954 cells within 24 hours. In combination with 5-FU, PHA-767491 exhibits enhanced cytotoxic effects in HCC cells, inducing significant apoptosis characterized by increased activation of caspase-3 and poly (ADP-ribose) polymerase fragmentation. It directly counteracts 5-FU-induced phosphorylation of Chk1 and reduces the expression of the anti-apoptotic protein, myeloid cell leukemia sequence 1 (Mcl-1). Furthermore, PHA-767491 (0-10 μM) reduces the viability of glioblastoma cells in a time- and dose-dependent manner, with IC50 values around 2.5 μM in U87-MG and U251-MG cells.
• In Vitro:
  PHA-767491 reduces Chk1 phosphorylation and increases in situ apoptosis in tumor tissues from nude mouse HCC xenograft slices.
• Cell Research:
  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.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Cyclin dependent kinase, CAY10572, CAY-10572, CAY 10572, Cdc7, CDK1, CDK, CDK2, CDK9, inhibit, GSK3, GSK-3β, Inhibitor, PHA767491, PHA-767491, PHA 767491

Compound Identifiers

PubChem CID

11715767