Kinase Inhibitors Involved in the Regulation of Autophagy: Molecular Concepts and Clinical Implications

• Published in: Current medicinal chemistry Vol. 30; no. 13; p. 1502
• Main Authors: Al-Huseini, Isehaq, Sirasanagandla, Srinivasa Rao, Babu, Kondaveeti Suresh, Sofin, Ramakrishna Gopala Sumesh, Das, Srijit
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2023
• Subjects: Autophagy - drug effects; Autophagy - immunology; Glycogen Synthase Kinase 3 - antagonists & inhibitors; Glycogen Synthase Kinase 3 - metabolism; Humans; Immunity, Innate; Protein Kinase Inhibitors - pharmacology; Signal Transduction; cellular degradation; molecular concepts; kinase inhibitors; signaling pathways; drug delivery; Autophagy
• ISSN: 1875-533X
• DOI: 10.2174/0929867329666220117114306

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 unwanted 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 elimination of various microbial pathogens. The process of autophagy has both positive and negative effects, and this pertains to any specific disease or its stage of progression. Autophagy 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-induced 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 autophagy by targeting specific kinases may form the mainstay of treatment of many diseases and lead the road to future drug discovery.