Discovery of Tricyclic Pyranochromenone as Novel Bruton's Tyrosine Kinase Inhibitors with in Vivo Antirheumatic Activity.

ABSTRACT: Bruton's tyrosine kinase (BTK) is an attractive target for treating patients with B cell malignancies and autoimmune diseases. Many BTK inhibitors have been identified; however, like other kinase inhibitors, they lack diversity in their core structures. Therefore, it is important to secure a novel scaffold that occupies the adenine-binding site of BTK. We screened an in-house library of natural products and their analogs via a biochemical assay to identify a novel scaffold for targeting BTK. A pyranochromenone scaffold, derived from a natural active component decursin, was found to be effective at targeting BTK and was selected for further optimization. A series of pyranochromenone analogs was synthesized through the modification of pyranochromenone at the C7 position. Pyranochromenone com

SUBMITTER: Cho H 

PROVIDER: S-EPMC7663272 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature