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CDK4/6 inhibitors: a brief overview and prospective research directions

The discovery of cyclin-dependent kinases (CDK) and their mechanism in regulating the cell cycle process was considered a game-changer in cancer therapy. Cell cycle arrest and apoptosis were both triggered by their inhibition. The CDK4/6 complex acts as a checkpoint during the cell cycle transition...

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Autores principales: Adon, Tenzin, Shanmugarajan, Dhivya, Kumar, Honnavalli Yogish
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040853/
https://www.ncbi.nlm.nih.gov/pubmed/35479560
http://dx.doi.org/10.1039/d1ra03820f
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author Adon, Tenzin
Shanmugarajan, Dhivya
Kumar, Honnavalli Yogish
author_facet Adon, Tenzin
Shanmugarajan, Dhivya
Kumar, Honnavalli Yogish
author_sort Adon, Tenzin
collection PubMed
description The discovery of cyclin-dependent kinases (CDK) and their mechanism in regulating the cell cycle process was considered a game-changer in cancer therapy. Cell cycle arrest and apoptosis were both triggered by their inhibition. The CDK4/6 complex acts as a checkpoint during the cell cycle transition from cell growth (G1) to DNA synthesis (S) phase and its deregulation or overexpression induces abnormal cell proliferation and cancer development. Consequently, targeting CDK4/6 has been proposed as a paradigm shift in the anticancer approach. The design and development of effective CDK4/6 inhibitors are increasingly becoming a promising cancer therapy evident with approved drugs such as palbociclib, ribociclib, and abemaciclib, etc. In this article, we explore the biological importance of CDK4/6 in cancer therapy, the development of resistance to monotherapy, and a short overview of PROTAC (Proteolysis Targeting Chimera), a unique and pioneering technique for degrading CDK4/6 enzymes. Overall, our prime focus is to discuss novel CDK4/6 inhibitors with diverse chemical classes and their correlation with computational studies.
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spelling pubmed-90408532022-04-26 CDK4/6 inhibitors: a brief overview and prospective research directions Adon, Tenzin Shanmugarajan, Dhivya Kumar, Honnavalli Yogish RSC Adv Chemistry The discovery of cyclin-dependent kinases (CDK) and their mechanism in regulating the cell cycle process was considered a game-changer in cancer therapy. Cell cycle arrest and apoptosis were both triggered by their inhibition. The CDK4/6 complex acts as a checkpoint during the cell cycle transition from cell growth (G1) to DNA synthesis (S) phase and its deregulation or overexpression induces abnormal cell proliferation and cancer development. Consequently, targeting CDK4/6 has been proposed as a paradigm shift in the anticancer approach. The design and development of effective CDK4/6 inhibitors are increasingly becoming a promising cancer therapy evident with approved drugs such as palbociclib, ribociclib, and abemaciclib, etc. In this article, we explore the biological importance of CDK4/6 in cancer therapy, the development of resistance to monotherapy, and a short overview of PROTAC (Proteolysis Targeting Chimera), a unique and pioneering technique for degrading CDK4/6 enzymes. Overall, our prime focus is to discuss novel CDK4/6 inhibitors with diverse chemical classes and their correlation with computational studies. The Royal Society of Chemistry 2021-09-01 /pmc/articles/PMC9040853/ /pubmed/35479560 http://dx.doi.org/10.1039/d1ra03820f Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Adon, Tenzin
Shanmugarajan, Dhivya
Kumar, Honnavalli Yogish
CDK4/6 inhibitors: a brief overview and prospective research directions
title CDK4/6 inhibitors: a brief overview and prospective research directions
title_full CDK4/6 inhibitors: a brief overview and prospective research directions
title_fullStr CDK4/6 inhibitors: a brief overview and prospective research directions
title_full_unstemmed CDK4/6 inhibitors: a brief overview and prospective research directions
title_short CDK4/6 inhibitors: a brief overview and prospective research directions
title_sort cdk4/6 inhibitors: a brief overview and prospective research directions
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040853/
https://www.ncbi.nlm.nih.gov/pubmed/35479560
http://dx.doi.org/10.1039/d1ra03820f
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