PHA-767491 hydrochloride

SKU: orb1300328

Description

PHA-767491 hydrochloride is a potent and selective ATP-competitive dual inhibitor of Cdc7 and CDK9 kinases, with IC50 values of 10 nM and 34 nM, respectively. It exhibits significant selectivity over related kinases and has been utilized in vitro and in vivo to study cell cycle progression, transcription, and oncology research.

Research Area

Metabolism Research

Key Properties

• CAS Number: 942425-68-5
• MW: 249.69
• Purity: 99.92% (May vary between batches)
• Formula: C₁₂H₁₂ClN₃O
• SMILES: Cl.O=C1NCCc2[nH]c(cc12)-c1ccncc1
• Target: Apoptosis,CDK,GSK-3
• Solubility: DMSO:4.62 mg/mL (18.5 mM);H2O:25 mg/mL (100.12 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (4 mM)

Bioactivity

• Target IC50:
  MK2:470 nM|Chk2:1100 nM|CDK1:250 nM|CDC7:10 nM|CDK5:460 nM|PLK1:980 nM|GSK-3β:220 nM|CDK2:240 nM|CDK9:34 nM
• In Vivo:
  PHA-767491 decreases Chk1 phosphorylation and enhances apoptosis directly within sections of tumor tissues from HCC xenografts in nude mice.
• In Vitro:
  PHA-767491 inhibits proliferation of HCC1954 cells (IC50: 0.64 μM) and Colo-205 cells (IC50: 1.3 μM). PHA-767491 is effective DDK inhibitors in vitro (IC50: 18.6 nM). PHA-767491 (2 μM) completely abolishes Mcm2 phosphorylation by 24 hours in HCC1954 cells . 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 line . PHA-767491 (0-10 μM) time- and dose-dependently decreases glioblastoma cell viability (IC50: about 2.5 μM) for U87-MG and U251-MG cells.
• 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

Apoptosis, CAY 10572, CAY 10572 Hydrochloride, CAY10572, CAY-10572, CAY10572 HCl, CAY10572 Hydrochloride, CAY-10572 hydrochloride, Cdc7, Cdk9, CDK, Cdk1, Cdk2, GSK-3β, GSK3, PHA 767491, PHA767491, PHA-767491, PHA767491 HCl, PHA-767491 HCl, PHA-767491 Hydrochloride

Compound Identifiers

PubChem CID

11715766