622864-54-4 Usage
Description
PD 407824 is an inhibitor of the checkpoint kinases Chk1 and WEE1 (IC50s = 47 and 97 nM, respectively). It is selective for Chk1 and WEE1 over PKC (IC50 = 3.4 μM), Cdk4 (IC50 = 3.75 μM), as well as c-Src and the PDGF and FGF receptors (IC50s = >50 μM for all), and other Cdks (IC50s = >50 μM). PD 407824 sensitizes SK-OV-3 and OVCAR-3 ovarian cancer cells, as well as cisplatin-resistant A2780cis cells, to cisplatin when used at a concentration of 0.5 μM. It also sensitizes C2C12 myoblasts to bone morphogenic protein 4 (BMP4) and, when used in combination with BMP4, inhibits myotube formation and induces myoblasts to differentiate into mature osteoblasts. PD 407824, in combination with BMP4, induces human embryonic stem cells to differentiate into cells with mesoderm or cytotrophoblast stem cell lineages.
Uses
Different sources of media describe the Uses of 622864-54-4 differently. You can refer to the following data:
1. PD-407824 is a Wee1/Chk1 inhibitor useful as cancer treatments.
2. PD-407824 has been used as a wee-1 inhibitor to study its effects on Xenopus laevis embryos. It has also been used as a checkpoint-1 (Chk-1) inhibitor to study its effects on the sensitivity of head and neck squamous carcinoma cells to gemcitabine.
Biological Activity
Selective inhibitor of checkpoint kinases Chk1 and Wee1 (IC 50 values are 47 and 97 nM respectively). Displays selectivity over a range of other protein kinases; IC 50 values are 3.4, 3.75, > 5, > 50, > 50 and > 50 μ M for PKC, CDK4, other CDKs, c-Src, PDGFR and FGFR respectively.
Biochem/physiol Actions
PD-407824 is a Wee1/Chk1 inhibitor.
Check Digit Verification of cas no
The CAS Registry Mumber 622864-54-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 6,2,2,8,6 and 4 respectively; the second part has 2 digits, 5 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 622864-54:
(8*6)+(7*2)+(6*2)+(5*8)+(4*6)+(3*4)+(2*5)+(1*4)=164
164 % 10 = 4
So 622864-54-4 is a valid CAS Registry Number.
InChI:InChI=1/C20H12N2O3/c23-11-6-7-14-13(8-11)16-15(21-14)9-12(10-4-2-1-3-5-10)17-18(16)20(25)22-19(17)24/h1-9,21,23H,(H,22,24,25)
622864-54-4Relevant articles and documents
4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione inhibitors of the checkpoint kinase Wee1. structure-activity relationships for chromophore modification and phenyl ring substitution
Palmer, Brian D.,Thompson, Andrew M.,Booth, R. John,Dobrusin, Ellen M.,Kraker, Alan J.,Lee, Ho H.,Lunney, Elizabeth A.,Mitchell, Lorna H.,Ortwine, Daniel F.,Smaill, Jeff B.,Swan, Leesa M.,Denny, William A.
, p. 4896 - 4911 (2007/10/03)
High-throughput screening has identified a novel class of inhibitors of the checkpoint kinase Wee1, which have potential for use in cancer chemotherapy. These inhibitors are based on a 4-phenylpyrrolo[3,4-c]-carbazole-1,3(2H,6H)- dione template and have been shown by X-ray crystallography to bind at the ATP site of the enzyme. An extensive study of the effects of substitution around this template has been carried out, which has identified substituents which lead to improvements in potency and selectivity for Wee1. While retention of the maleimide ring and pendant 4-phenyl group is necessary for potency, replacement of the carbazole nitrogen by oxygen is well tolerated and results in improved Wee1 selectivity against the related checkpoint kinase Chk1. Wee1 potency and selectivity are also enhanced by the incorporation of lipophilic functionality at the 2′-position of the 4-phenyl ring, and Wee1 selectivity against Chk1 is favored by C3-C5 alkyl substitution of the carbazole nitrogen. These studies provide a basis for the design of active analogues of the pyrrolocarbazole lead with improved physical properties.
