Small Molecule Kinase Inhibitor Drugs (1995–2021): Medical Indication, Pharmacology, and Synthesis

Abstract

The central role of dysregulated kinase activity inthe etiology of progressive disorders, including cancer, has fosteredincremental efforts on drug discovery programs over the past 40years. As a result, kinase inhibitors are today one of the mostimportant classes of drugs. The FDA approved 73 small moleculekinase inhibitor drugs until September 2021, and additionalinhibitors were approved by other regulatory agencies during thattime. To complement the published literature on clinical kinaseinhibitors, we have prepared a review that recaps this large data setinto an accessible format for the medicinal chemistry community.Along with the therapeutic and pharmacological properties of eachkinase inhibitor approved across the world until 2020, we provide the synthesis routes originally used during the discovery phase,many of which were only available in patent applications. In the last section, we also provide an update on kinase inhibitor drugsapproved in 2021.