38940-11-3

GPR52 is an orphan G protein-coupled receptor (GPCR) that has been recently implicated as a potential drug target of Huntington's disease (HD), an incurable monogenic neurodegenerative disorder. In this research, we found that striatal knockdown of GPR52 reduces mHTT levels in adult HdhQ140 mice, validating GPR52 as an HD target. In addition, we discovered a highly potent and specific GPR52 antagonist Comp-43 with an IC50 value of 0.63 μM by a structure-activity relationship (SAR) study. Further studies showed that Comp-43 reduces mHTT levels by targeting GPR52 and promotes survival of mouse primary striatal neurons. Moreover, in vivo study showed that Comp-43 not only reduces mHTT levels but also rescues HD-related phenotypes in HdhQ140 mice. Taken together, our study confirms that inhibition of GPR52 is a promising strategy for HD therapy, and the GPR52 antagonist Comp-43 might serve as a lead compound for further investigation.

Alnustone-like compounds are promising inhibitors for estrogen receptor α (ER- α) , which is a novel cancer therapeutic target. Therefore, 10 alnustone-like compounds with substituents at the phenyl rings were synthesized by condensation of 4-phenyl-2-butanones and cinnamaldehydes via in situ enamination. The compounds displayed either protective activity or inhibited cell growth and proliferation of human breast cancer cells. Molecular docking studies indicated that the synthesized compounds interact with ER- α efficiently. In this work, the protective and inhibitive roles of the synthesized compounds were related to their functional groups and to their binding mode of action on ER- α protein. The compounds are potential drug candidates as ER- α antagonists.

An efficient synthesis of physiologically interesting diarylheptanoids has been carried out through direct C-acylation using diethyl phosphorocyanidate (DEPC) followed by Grignard reactions with aldehydes.Keywords - diarylheptanoid; C-acylation; diethyl p

Four new diarylheptanoids ha