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PHA 767491 hydrochloride
ATP-competitive cyclin-dependent kinase (cdk) inhibitor (reported IC50 values are 0.034 - 0.75, 0.24 - 1.2, 0.25 - 1.1 and 0.46 - 1 μM for cdk9, cdk2, cdk1 and cdk5, respectively). Also inhibits mitogen-activated protein kinase-activated protein kinase-2 (MK2; IC50 = 171 nM). Prevents initiation of DNA replication. Inhibits cell proliferation in a variety of human cell lines and induces apoptosis in a p53-independent manner in vivo.
|Storage||Desiccate at RT|
The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.
|Solvent||Max Conc. mg/mL||Max Conc. mM|
Preparing Stock Solutions
The following data is based on the product molecular weight 249.7. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||4 mL||20.02 mL||40.05 mL|
|5 mM||0.8 mL||4 mL||8.01 mL|
|10 mM||0.4 mL||2 mL||4 mL|
|50 mM||0.08 mL||0.4 mL||0.8 mL|
References are publications that support the biological activity of the product.
Anderson et al (2007) Pyrrolopyridine inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2). J.Med.Chem. 50 2647 PMID: 17480064
Jackson (2008) Stopping replication, at the beginning. Nature Chem.Biol. 4 331
Montagnoli et al (2008) A cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumour activity. Nature Chem.Biol. 4 357
Jorda et al (2018) How selective are pharmacological inhibitors of cell-cycle-regulating cyclin-dependent kinases? J.Med.Chem. 61 9105 PMID: 30234987
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5 Citations for PHA 767491 hydrochloride
Citations are publications that use Tocris products. Selected citations for PHA 767491 hydrochloride include:
FitzGerald et al (2014) A high through-put screen for small molecules modulating MCM2 phosphorylation identifies Ryuvidine as an inducer of the DNA damage response. PLoS One 9 e98891 PMID: 24902048
Wu et al (2016) DDK dependent regulation of TOP2A at centromeres revealed by a chemical genetics approach. Nucleic Acids Res 44 8786 PMID: 27407105
Bartley et al (2016) Mammalian FMRP S499 Is Phosphorylated by CK2 and Promotes Secondary Phosphorylation of FMRP. Eneuro 3 PMID: 27957526
Liachko et al (2013) CDC7 inhibition blocks pathological TDP-43 phosphorylation and neurodegeneration. Ann Neurol 74 39 PMID: 23424178
Gardner et al (2011) Geminin overexpression prevents the completion of topoisomerase IIα chromosome decatenation, leading to aneuploidy in human mammary epithelial cells. Breast Cancer Res 13 R53 PMID: 21595939
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Literature in this Area
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Cell Cycle & DNA Damage Repair Poster
In normal cells, each stage of the cell cycle is tightly regulated, however in cancer cells many genes and proteins that are involved in the regulation of the cell cycle are mutated or over expressed. Adapted from the 2015 Cancer Product Guide, Edition 3, this poster summarizes the stages of the cell cycle and DNA repair. It also highlights strategies for enhancing replicative stress in cancer cells to force mitotic catastrophe and cell death.