AI Article Synopsis
- BTK is a key enzyme involved in B-cell disorders, and targeting it has been shown to help treat these conditions.
- Researchers developed a new series of BTK inhibitors using an imidazo[4,5-b]pyridine design, leading to a promising compound with high potency and selectivity.
- The lead compound showed strong inhibitory effects in human blood and effective results in a rat model, along with good pharmacokinetic properties.
Article Abstract
Bruton's tyrosine kinase (BTK) is a cytoplasmic, non-receptor tyrosine kinase member of the TEC family of tyrosine kinases. Pre-clinical and clinical data have shown that targeting BTK can be used for the treatment for B-cell disorders. Here we disclose the discovery of a novel imidazo[4,5-b]pyridine series of potent, selective reversible BTK inhibitors through a rational design approach. From a starting hit molecule 1, medicinal chemistry optimization led to the development of a lead compound 30, which exhibited 58 nM BTK inhibitory potency in human whole blood and high kinome selectivity. Additionally, the compound demonstrated favorable pharmacokinetics (PK), and showed potent dose-dependent efficacy in a rat CIA model.
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| http://dx.doi.org/10.1016/j.bmc.2021.116163 | DOI Listing |
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