Protein kinases as targets for developing anticancer agents from marine organisms

Biochim Biophys Acta Gen Subj. 2021 Jan;1865(1):129759. doi: 10.1016/j.bbagen.2020.129759. Epub 2020 Oct 8.

Abstract

Protein kinases play a fundamental role in the intracellular transduction because of their ability to phosphorylate plethora of proteins. Over the past three decades, numerous protein kinase inhibitors have been identified and are being used clinically successfully. The biodiversity of marine organisms provides a rich source for the discovery and development of novel anticancer agents in the treatment of human malignancies and a lot of bioactive ingredients from marine organisms display anticancer effects by affecting the protein kinases-mediated pathways. In the present mini-review, anticancer compounds from marine source were reviewed and discussed in context of their targeted pathways associated with protein kinases and the progress of these compounds as anticancer agents in recent five years were emphasized. The molecular entities and their modes of actions were presented. We focused on protein kinases-mediated signaling pathways including PI3K/Akt/mTOR, p38 MAPK, and EGFR. The marine compounds targeting special pathways of protein kinases were highlighted. We have also discussed the existing challenges and prospects related to design and development of novel protein kinase inhibitors from marine sources.

Keywords: Anticancer activity; EGFR; Marine organisms; P13K/Akt/mTOR; Protein kinase inhibitors; p38 MAPK.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Aquatic Organisms
  • Biological Products / chemistry*
  • Biological Products / pharmacology*
  • Biological Products / therapeutic use
  • Drug Discovery
  • ErbB Receptors / metabolism
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antineoplastic Agents
  • Biological Products
  • Protein Kinase Inhibitors
  • ErbB Receptors
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • p38 Mitogen-Activated Protein Kinases