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Optimization of novel reversible Bruton's tyrosine kinase inhibitors identified using Tethering-fragment-based screens. | LitMetric

AI Article Synopsis

Article Abstract

Since the approval of ibrutinib for the treatment of B-cell malignancies in 2012, numerous clinical trials have been reported using covalent inhibitors to target Bruton's tyrosine kinase (BTK) for oncology indications. However, a formidable challenge for the pharmaceutical industry has been the identification of reversible, selective, potent molecules for inhibition of BTK. Herein, we report application of Tethering-fragment-based screens to identify low molecular weight fragments which were further optimized to improve on-target potency and ADME properties leading to the discovery of reversible, selective, potent BTK inhibitors suitable for pre-clinical proof-of-concept studies.

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http://dx.doi.org/10.1016/j.bmc.2019.05.021DOI Listing

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