845714-00-3 Usage
Description
PHA 767491 hydrochloride is a potent and selective ATP-competitive dual inhibitor of Cdc7 kinase and Cdk9, playing a crucial role in the regulation of the cell cycle and transcriptional processes.
Uses
Used in Oncologic Therapeutics:
PHA 767491 hydrochloride is used as an oncologic therapeutic agent for the treatment of various cancers. It inhibits Cdc7 kinase, leading to a blockade of DNA synthesis in human cell lines and funneling tumor cells into the apoptotic pathway in a p53-independent manner. This pharmacological inhibition can be an effective strategy for developing oncologic therapeutics.
Used in Cell Cycle Regulation:
PHA 767491 hydrochloride is used as a cell cycle regulator, as it blocks DNA synthesis and affects the phosphorylation of the replicative DNA helicase at Cdc7-dependent phosphory sites. This action inhibits cell proliferation in a variety of human cell lines.
Used in Transcription Regulation:
PHA 767491 hydrochloride is used as a transcription regulator, as it inhibits Cdk9, a kinase involved in the phosphorylation of RNA polymerase II and in transcriptional regulation of gene expression. This inhibition can have significant effects on cellular processes and gene expression.
Used in Research Applications:
PHA 767491 hydrochloride is used as a research tool for studying the roles of Cdc7 kinase and Cdk9 in various biological processes. Its potent inhibitory effects on these kinases make it a valuable compound for investigating their functions and potential therapeutic targets in different diseases, including cancer.
Biological Activity
Potent, ATP-competitive dual cdc7/cdk9 inhibitor (IC 50 values are 10 and 34 nM respectively) that prevents initiation of DNA replication. Inhibits cell proliferation in a variety of human cell lines (IC 50 ~ 0.86 - 5.87 μ M) and induces apoptosis in a p53-independent manner in vivo . Also inhibits mitogen-activated protein kinase-activated protein kinase-2 (MK-2) (IC 50 = 171 nM).
Check Digit Verification of cas no
The CAS Registry Mumber 845714-00-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,4,5,7,1 and 4 respectively; the second part has 2 digits, 0 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 845714-00:
(8*8)+(7*4)+(6*5)+(5*7)+(4*1)+(3*4)+(2*0)+(1*0)=173
173 % 10 = 3
So 845714-00-3 is a valid CAS Registry Number.
InChI:InChI=1/C12H11N3O.ClH/c16-12-9-7-11(8-1-4-13-5-2-8)15-10(9)3-6-14-12;/h1-2,4-5,7,15H,3,6H2,(H,14,16);1H
845714-00-3Relevant articles and documents
Development of dihydropyrrolopyridinone-based PKN2/PRK2 chemical tools to enable drug discovery
Elkins, Jonathan M.,Fala, Angela M.,Ficu, Mihaela P.,Massirer, Katlin B.,Pennicott, Lewis E.,Reuillon, Tristan D.,Scott, Fiona,Takarada, Jessica E.,Ward, Simon E.,Cou?ago, Rafael M.
supporting information, (2022/02/05)
The Protein Kinase N proteins (PKN1, PKN2 and PKN3) are Rho GTPase effectors. They are involved in several biological processes such as cytoskeleton organization, cell mobility, adhesion, and cell cycle. Recently PKNs have been reported as essential for s
Pyrrolopyridine inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2)
Anderson, David R.,Meyers, Marvin J.,Vernier, William F.,Mahoney, Matthew W.,Kurumbail, Ravi G.,Caspers, Nicole,Poda, Gennadiy I.,Schindler, John F.,Reitz, David B.,Mourey, Robert J.
, p. 2647 - 2654 (2008/02/04)
A new class of potent kinase inhibitors selective for mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2 or MK-2) for the treatment of rheumatoid arthritis has been prepared and evaluated. These inhibitors have IC50 values as low as 10 nM against the target and have good selectivity profiles against a number of kinases including CDK2, ERK, JNK, and p38. These MK-2 inhibitors have been shown to suppress TNFα production in U397 cells and to be efficacious in an acute inflammation model. The structure-activity relationships of this series, the selectivity for MK-2 and their activity in both in vitro and in vivo models are discussed. The observed selectivity is discussed with the aid of an MK-2/inhibitor crystal structure.
