Discovery of Potent and Exquisitely Selective Inhibitors of Kinase CK1 with Tunable Isoform Selectivity

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F23%3A00079773" target="_blank" >RIV/00159816:_____/23:00079773 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14310/23:00130385

Result on the web

<a href="https://onlinelibrary.wiley.com/doi/10.1002/anie.202217532" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1002/anie.202217532</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/anie.202217532" target="_blank" >10.1002/anie.202217532</a>

Result language

angličtina

Original language name

Discovery of Potent and Exquisitely Selective Inhibitors of Kinase CK1 with Tunable Isoform Selectivity

Original language description

Casein kinases 1 (CK1) are key signaling molecules that have emerged recently as attractive therapeutic targets in particular for the treatment of hematological malignancies. Herein, we report the identification of a new class of potent and highly selective inhibitors of CK1 alpha, delta and epsilon. Based on their optimal in vitro and in vivo profiles and their exclusive selectivity, MU1250, MU1500 and MU1742 were selected as quality chemical probes for those CK1 isoforms. At proper concentrations, MU1250 and MU1500 allow for specific targeting of CK1 delta or dual inhibition of CK1 delta/epsilon in cells. The compound MU1742 also efficiently inhibits CK1 alpha and, to our knowledge, represents the first potent and highly selective inhibitor of this enzyme. In addition, we demonstrate that the central 1H-pyrrolo[2,3-b]pyridine-imidazole pharmacophore can be used as the basis of highly selective inhibitors of other therapeutically relevant protein kinases, e.g. p38 alpha, as exemplified by the compound MU1299.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

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Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Angewandte Chemie-International Edition

ISSN

1433-7851

e-ISSN

1521-3773

Volume of the periodical

62

Issue of the periodical within the volume

11

Country of publishing house

DE - GERMANY

Number of pages

7

Pages from-to

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UT code for WoS article

000924089800001

EID of the result in the Scopus database

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