Pyrazolo[4,3-d]pyrimidine Bioisostere of Roscovitine: Evaluation of a Novel Selective Inhibitor of Cyclin-Dependent Kinases with Antiproliferative Activity

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F11%3A10222088" target="_blank" >RIV/61989592:15110/11:10222088 - isvavai.cz</a>
Alternative codes found
RIV/61388971:_____/11:00368592 RIV/61989592:15310/11:10222088 RIV/61389030:_____/11:00368592
Result on the web
<a href="http://dx.doi.org/10.1021/jm200064p" target="_blank" >http://dx.doi.org/10.1021/jm200064p</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/jm200064p" target="_blank" >10.1021/jm200064p</a>

Result language
angličtina
Original language name
Pyrazolo[4,3-d]pyrimidine Bioisostere of Roscovitine: Evaluation of a Novel Selective Inhibitor of Cyclin-Dependent Kinases with Antiproliferative Activity
Original language description
Inhibition of cyclin-dependent kinases (CDKs) with small molecules has been suggested as a strategy for treatment of cancer, based on deregulation of CDKs commonly found in many types of human tumors. Here, a new potent CDK2 inhibitor with pyrazolo[4,3-d]pyrimidine scaffold has been synthesized, characterized, and evaluated in cellular and biochemical assays. 7-Benzylamino-5(R)-[2-(hydroxymethyl)-propyl]amino-3-isopropyl-1(2)H-pyrazolo[4,3-d]pyrimidine, compound 7, was prepared as a bioisostere of the well-known CDK inhibitor roscovitine. An X-ray crystal structure of compound 7 bound to CDK2 has been determined, revealing a binding mode similar to that of roscovitine. Protein kinase selectivity profile of compound 7 and its biological arrest, dephosphorylation of the retinoblastoma protein, accumulation of the tumor suppressor protein p53, induction of apoptosis, inhibition of homologous recombination) are consistent with CDK inhibition as a primary mode of action.
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CE - Biochemistry
OECD FORD branch
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Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)

Publication year
2011
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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