845714-00-3 Usage
Uses
Different sources of media describe the Uses of 845714-00-3 differently. You can refer to the following data:
1. Cdc7 kinase is a key regulator of the S-phase of the cell cycle. It is known to promote the activity of DNA replication origins in eukaryotic organisms. Inhibition of Cdc7 kinase causes blockade of DNA synthesis in human cell lines. Tumor cells are then funneled into the apoptotic pathway in a p53-independent manner. Pharmacological inhibition of Cdc7 kinase can be an effective strategy for the development of oncologic therapeutics useful for treatment of cancers. PHA 767491 HYDROCHLORIDE is a potent inhibitor of Cdc7 kinase with an IC50 value of 10 nM in the presence of 1.5 μM ATP. At 10 μM, PHA 767491 HYDROCHLORIDE induces apoptotic cell death in multiple cancer cell types. PHA 767491 HYDROCHLORIDE also inhibits Cdk9, a kinase involved in the phosphorylation of RNA polymerase II and in transcriptional regulation of gene expression, with an IC50 value of 34 nM.[Cayman Chemical]
2. PHA 767491 is a potent and selective ATP-competitive dual inhibitor cdc7/cdk9. It blocks DNA synthesis and affects the phosphorylation of the replicative DNA helicase at Cdc7-dependent phosphorylation sites. Inhibits cell proliferation in a variety of human cell lines and induces apoptosis in a p53-independent manner in vivo. Also inhibits mitogen-activated protein kinase-activated protein kinase-2 (MK-2).
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.
