Generic placeholder image

Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Targeting Serine / Threonine Protein Kinase B / Akt and Cell-cycle Checkpoint Kinases for Treating Cancer

Author(s): Qun Li and Gui-Dong Zhu

Volume 2, Issue 9, 2002

Page: [939 - 971] Pages: 33

DOI: 10.2174/1568026023393318

Price: $65


Over the past decade, protein kinases have emerged as a group of molecular targets with the potential to be “cancer-specific”, allowing the selective targeting of cancer cells versus normal cells. These selective anticancer drugs would eliminate the cytotoxic side effects that are associated with conventional cancer chemotherapy. This article will focus on two emerging and less-explored protein serine / threonine kinase targets: PKB / Akt and checkpoint kinase 1 (Chk1). Protein kinase B / Akts are a group of serine / threonine kinases that are overexpressed in a variety of human tumors. An Akt inhibitor would target the imbalance of pro-versus anti-apoptosis regulation in cancerous as compared to healthy cells. Thus, a greater therapeutic window than conventional cytotoxic chemotherapy is expected. Cell-cycle checkpoints have become attractive targets since some of them, such as the G1 / S checkpoint, are defective in most tumor cells. Inhibition of one or more of the remaining checkpoint(s) could make cancerous cells more sensitive than healthy cells toward DNA damaging agents or radiation therapy. Among the checkpoint kinases, Chk1 appears to be an attractive molecular target. Chk1 blocks the activation of the Cdc2-cyclin B kinase complex, and hence entry into mitosis, by disrupting the translocation of the phosphatase Cdc25C from the cyotoplasm to the nucleus. A limited number of small molecule inhibitors in this emerging field and their mode of action will be reviewed.

Keywords: protein kinase, treating cancer, anti-apoptosis, cancer chemotherapy, combinatorial approach, n-terminal pleckstrin homology, caffeine, cell-based assay

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy