Tyrosine Kinase Receptors and Their Pharmacology: A Comprehensive Review of Mechanisms, Inhibitors, and Therapeutic Applications

Abstract

Receptor tyrosine kinases (RTKs) constitute one of the most important classes of cell-surface enzymes governing proliferation, migration, survival and metabolism in multicellular organisms. Aberrant signalling through these receptors is now recognised as a unifying molecular feature of cancer, fibrosis, metabolic disorders and chronic inflammation. Over the last three decades small-molecule kinase inhibitors and monoclonal antibodies directed at RTKs have become cornerstone agents of modern precision medicine. The present review summarises the biology of the major RTK families, the molecular mechanism of action of clinically important inhibitors, the structural basis of inhibitor binding, and the spectrum of diseases in which these drugs are deployed. Special emphasis is placed on the molecular pharmacology of imatinib, gefitinib, erlotinib, osimertinib, lapatinib, neratinib, trastuzumab, bevacizumab, sunitinib, sorafenib, crizotinib, ceritinib, alectinib, brigatinib, capmatinib, selpercatinib, pralsetinib, larotrectinib, entrectinib, erdafitinib, pemigatinib, ruxolitinib, tofacitinib, nintedanib and vemurafenib. Approximately 8,600 words are distributed across twenty sections, each of roughly 430 words, following the structure described below.