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

• Main Authors: Ahmed Elkamhawy, Eslam M. H. Ali, Kyeong Lee
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2021-01-01
• Series: Journal of Enzyme Inhibition and Medicinal Chemistry
• Subjects: lck inhibitors; structure-activity relationship (sar); src family kinase; lymphocyte-specific protein tyrosine kinase (lck); molecular modelling
• Online Access: http://dx.doi.org/10.1080/14756366.2021.1937143

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.