The Development of BTK Inhibitors: A Five-Year Update

• Published in: Molecules (Basel, Switzerland) Vol. 26; no. 23; p. 7411
• Main Authors: Tasso, Bruno, Spallarossa, Andrea, Russo, Eleonora, Brullo, Chiara
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06-12-2021; MDPI
• Subjects: (ir)reversible inhibitors; Agammaglobulinaemia Tyrosine Kinase - antagonists & inhibitors; Agammaglobulinaemia Tyrosine Kinase - chemistry; Agammaglobulinaemia Tyrosine Kinase - classification; Agammaglobulinaemia Tyrosine Kinase - metabolism; Animals; Arthritis; Autoimmune diseases; Autoimmune Diseases - drug therapy; Autoimmune Diseases - metabolism; B-cell malignancies; B-Lymphocytes - metabolism; Binding sites; Bruton's tyrosine kinase; Bruton’s kinase; Cancer therapies; Chemical bonds; Chemical compounds; Coronaviruses; COVID-19; Edema; Enzymes; Humans; Inhibitors; Inhibitory Concentration 50; Kinases; Leukemia; Lymphoma; medicinal chemistry; Neoplasms - drug therapy; Neoplasms - metabolism; Pharmacology; Protein Kinase Inhibitors - therapeutic use; Protein-tyrosine kinase; Proteins; Review; Side effects; small molecules; Treatment Outcome; Tyrosine; China; (ir)reversible inhibitors; autoimmune diseases; Bruton’s kinase; medicinal chemistry; small molecules; B-cell malignancies
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26237411

Bruton's tyrosine kinase (BTK) represented, in the past ten years, an important target for the development of new therapeutic agents that could be useful for cancer and autoimmune disorders. To date, five compounds, able to block BTK in an irreversible manner, have been launched in the market, whereas many reversible BTK inhibitors (BTKIs), with reduced side effects that are more useful for long-term administration in autoimmune disorders, are under clinical investigation. Despite the presence in the literature of many articles and reviews, studies on BTK function and BTKIs are of great interest for pharmaceutical companies as well as academia. This review is focused on compounds that have appeared in the literature from 2017 that are able to block BTK in an irreversible or reversible manner; also, new promising tunable irreversible inhibitors, as well as PROTAC molecules, have been reported. This summary could improve the knowledge of the chemical diversity of BTKIs and provide information for future studies, particularly from the medicinal chemistry point of view. Data reported here are collected from different databases (Scifinder, Web of Science, Scopus, Google Scholar, and Pubmed) using "BTK" and "BTK inhibitors" as keywords.