Cyclin dependent kinase (CDK) inhibitors as anticancer drugs: Recent advances (2015-2019).

Abstract

Sustained proliferative capacity and gene dysregulation are hallmarks of cancer. In mammalian cells, cyclin-dependent kinases (CDKs) control critical cell cycle checkpoints and key transcriptional events in response to extracellular and intracellular signals leading to proliferation. Significant clinical activity for the treatment of hormone receptor positive metastatic breast cancer has been demonstrated by palbociclib, ribociclib and abemaciclib, dual CDK4/6 inhibitors recently FDA-approved. SY-1365, a CDK7 inhibitor has shown initial encouraging data in phase I for solid tumors treatment. These results have rejuvenated the CDKs research field. This review provides an overview of relevant advances on CDK inhibitor research since 2015 to 2019, with special emphasis on transcriptional CDK inhibitors, new emerging strategies such as target protein degradation and compounds under clinical evaluation.

• Authors: Concepción Sánchez-Martínez, María José Lallena, Sonia Gutiérrez Sanfeliciano, Alfonso de Dios
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 29 Issue 20 Pg. 126637 (10 15 2019) ISSN: 1464-3405 [Electronic] England
• PMID: 31477350 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Aminopyridines
• Antineoplastic Agents
• Benzimidazoles
• Indoles
• Piperazines
• Protein Kinase Inhibitors
• Purines
• Pyridines
• Pyrimidines
• Transcription Factors
• abemaciclib
• mevociclib
• Cyclin-Dependent Kinases
• palbociclib
• ribociclib

Topics

• Aminopyridines (chemistry, pharmacology)
• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Benzimidazoles (chemistry, pharmacology)
• Breast Neoplasms (drug therapy)
• Cell Cycle Checkpoints (drug effects)
• Cyclin-Dependent Kinases (antagonists & inhibitors)
• Drug Discovery
• Humans
• Indoles (chemistry, pharmacology)
• Piperazines (chemistry, pharmacology)
• Protein Kinase Inhibitors (chemistry, pharmacology)
• Purines (chemistry, pharmacology)
• Pyridines (chemistry, pharmacology)
• Pyrimidines (chemistry, pharmacology)
• Transcription Factors (metabolism)