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PHA-767491

In stock
Catalog No.
A3721
Cdc7/cdk9 inhibitor, potent, ATP-competitive
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$85.00
In stock
10mg
$65.00
In stock
50mg
$259.00
In stock

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Background

PHA-767491 is a small-molecule inhibitor of Cdc7 kinase with IC50 value of 10 nM [1].
In the process of DNA synthesis, Cdc7 kinase is critical to the activation of replication origins. It phosphorylates several subunits of mini chromosome maintenance proteins (MCMs), especially the Mcm2 at Ser40 and Ser53 sites, which constitute the replicative DNA helicase. Cdc7 is overexpressed in tumor cells and tumor specimens, therefore the Cdc7 inhibitors are developed as anticancer agents. As a small-molecule Cdc7 inhibitor, PHA-767491 exerted antitumor activity through a different mechanism than other drugs target DNA replication. PHA-767491 competed with ATP for binding to Cdc7 and showed an IC50 value of 10 nM in the presence of 1.5 μM ATP [1].
PHA-767491 is a selective inhibitor. It showed no inhibitory effect on 15 kinases when tested against a panel of 38 serine/theronine and tyrosine kinases. However, it inhibited cdk1, cdk2 and GSK-3β with 20-fold less potency. Besides that, PHA-767491 was found to have inhibitory effect on Cdk9 with IC50 value of 34 nM, which made it be regarded as a dual inhibitor of Cdk7/9 kinase. When treated to a panel of 61 human cell lines, PHA-767491 caused cell proliferation inhibition with an average IC50 value of 3.17μM. It killed cells both p53-positive and p53-negative. Among the exceptions, NHDF and MCF7 cells were resistant to PHA-767491. K562 cells were less sensitive to PHA-767491 [1].
In mice bearing implanted tumors derived from HL60 cell lines, administration of PHA-767491 at dose of 20 and 30 mg/kg twice a day reduced tumor volume dose-dependently. PHA-767491 administration also resulted in 50% tumor growth inhibition in xenograft models of A2780 ovary carcinoma, HCT-116 colon carcinoma or Mx-1 mammary adenocarcinoma [1].
Reference:
[1] Montagnoli A, Valsasina B, Croci V, et al. A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity. Nature chemical biology, 2008, 4(6): 357-365.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt213.24
Cas No.845714-00-3
FormulaC12H11N3O
SynonymsCAY10572;PHA767491;PHA 767491;CAY-10572;CAY 10572
Solubility≥10.65 mg/mL in DMSO, <2.33 mg/mL in EtOH, <2.23 mg/mL in H2O
Chemical Name2-pyridin-4-yl-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one
SDFDownload SDF
Canonical SMILESC1CNC(=O)C2=C1NC(=C2)C3=CC=NC=C3
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Biological Activity

Description PHA-767491 is a potent, ATP-competitive inhibitor of cdc7 and cdk9 with 10 nM and 34 nM, respectively.
Targets cdc7 cdk9        
IC50 10 nM 34 nM        

Quality Control

Chemical structure

PHA-767491