Identification of a rhodanine derivative BML-260 as a potent stimulator of UCP1 expression.

ABSTRACT: Identification of proper agents to increase or activate UCP1⁺ cells in adipose tissues remains a potent therapeutic strategy to combat obesity. Screening systems for UCP1 activators have been previously established and allow for unbiased discovery of effective compound(s). Methods: A previously established Ucp1-2A-GFP reporter system was applied to a chemical library containing 33 phosphatase inhibitors. Compounds that can significantly activate UCP1 expression were further tested in vivo in mouse adipose tissues. Possible underlying mechanism was explored via RNA profiling, CMAP analysis, CRISPR targeting as well as inhibitor treatments. Results: We identified BML-260, a known potent inhibitor of the dual-specific phosphatase JSP-1, that significantl

SUBMITTER: Feng Z 

PROVIDER: S-EPMC6587176 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature