Kinase Inhibitors Involved in the Regulation of Autophagy: Molecular concepts and clinical implications

Isehaq Al-Huseini, Srinivasa Rao Sirasanagandla, Kondaveeti Suresh Babu, Ramakrishna Gopala Sumesh Sofin, Srijit Das*

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

All cells and intracellular components are remodeled and recycled in order to replace the old and damaged cells. Autophagy is a process by which damaged, and un-wanted cells are degraded in the lysosomes. There are three different types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy. Autophagy has an effect on adaptive and innate immunity, suppression of any tumour, and the elimina-tion of various microbial pathogens. The process of autophagy has both positive and neg-ative effects, and this pertains to any specific disease or its stage of progression. Autopha-gy involves various processes which are controlled by various signaling pathways, such as Jun N-terminal kinase, GSK3, ERK1, Leucine-rich repeat kinase 2, and PTEN-in-duced putative kinase 1 and parkin RBR E3. Protein kinases are also important for the regulation of autophagy as they regulate the process of autophagy either by activation or inhibition. The present review discusses the kinase catalyzed phosphorylated reactions, the kinase inhibitors, types of protein kinase inhibitors and their binding properties to protein kinase domains, the structures of active and inactive kinases, and the hydrophobic spine structures in active and inactive protein kinase domains. The intervention of au-tophagy by targeting specific kinases may form the mainstay of treatment of many diseases and lead the road to future drug discovery.

Original languageEnglish
Pages (from-to)1502-1528
Number of pages27
JournalCurrent Medicinal Chemistry
Volume30
Issue number13
Early online dateJan 17 2022
DOIs
Publication statusPublished - Apr 1 2023

Keywords

  • Autophagy
  • cellular degradation
  • drug delivery
  • kinase inhibitors
  • molecular concepts
  • signaling pathways

ASJC Scopus subject areas

  • Drug Discovery
  • Molecular Medicine
  • Biochemistry
  • Pharmacology
  • Organic Chemistry

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