New horizons in drug discovery of lymphocyte-specific protein tyrosine kinase (Lck) inhibitors: a decade review (2011–2021) focussing on structure–activity relationship (SAR) and docking insights. (1st January 2021)

• Record Type: Journal Article
• Authors: Elkamhawy, Ahmed; Ali, Eslam M. H.; Lee, Kyeong
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 36:Number 1(2021)
• Page Start: 1572
• Page End: 1600
• Publication Date: 2021-01-01
• Subjects: Lck inhibitors -- structure-activity relationship (SAR) -- Src family kinase -- lymphocyte-specific protein tyrosine kinase (Lck) -- molecular modelling; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2021.1937143
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: Lymphocyte-specific protein tyrosine kinase (Lck), a non-receptor Src family kinase, has a vital role in various cellular processes such as cell cycle control, cell adhesion, motility, proliferation, and differentiation. Lck is reported as a key factor regulating the functions of T-cell including the initiation of TCR signalling, T-cell development, in addition to T-cell homeostasis. Alteration in expression and activity of Lck results in numerous disorders such as cancer, asthma, diabetes, rheumatoid arthritis, atherosclerosis, and neuronal diseases. Accordingly, Lck has emerged as a novel target against different diseases. Herein, we amass the research efforts in literature and pharmaceutical patents during the last decade to develop new Lck inhibitors. Additionally, structure-activity relationship studies (SAR) and docking models of these new inhibitors within the active site of Lck were demonstrated offering deep insights into their different binding modes in a step towards the identification of more potent, selective, and safe Lck inhibitors.