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Ref Type Journal Article
PMID (34529443)
Authors Kawahata W, Asami T, Kiyoi T, Irie T, Kashimoto S, Furuichi H, Sawa M
Title Discovery of AS-1763: A Potent, Selective, Noncovalent, and Orally Available Inhibitor of Bruton's Tyrosine Kinase.
Journal Vol Issue Date Pages Journal Short Title
Journal of medicinal chemistry 64 19 2021 Oct 14 14129-14141 J Med Chem
URL
Abstract Text Although Bruton's tyrosine kinase (BTK) has been recognized as a validated drug target for the treatment of B-cell malignances, the emergence of clinical resistance to the first-generation covalent BTK inhibitors is becoming a serious concern. As a part of our effort to develop noncovalent BTK inhibitors, a series of novel pyrrolopyrimidines was identified as noncovalent inhibitors of both the wild-type and C481S mutant BTKs. Subsequent lead optimization led to the identification of an orally available, potent, and selective BTK inhibitor 13f (AS-1763) as a next-generation noncovalent BTK inhibitor. With significant efficacies in vivo tumor xenograft models, AS-1763 has advanced to phase 1 clinical trials.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
AS-1763 AS-1763 1 1
Drug Name Trade Name Synonyms Drug Classes Drug Description
AS-1763 AS 1763|AS1763|BN 102|BN-102|BN102|docirbrutinib BTK inhibitor 39 AS-1763 inhibits BTK, which potentially decreases tumor cell growth (PMID: 34529443).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BTK C481S diffuse large B-cell lymphoma activated B-cell type sensitive AS-1763 Preclinical - Cell line xenograft Actionable In a preclinical study, AS-1763 inhibited proliferation of an activated B cell-like (ABC) diffuse large B-cell lymphoma cell line expressing BTK C481S in culture and inhibited tumor growth in a cell line xenograft model (PMID: 34529443). 34529443