17827-60-0Relevant articles and documents
GPR52 Antagonist Reduces Huntingtin Levels and Ameliorates Huntington's Disease-Related Phenotypes
Wang, Congcong,Zhang, Yu-Fang,Guo, Shimeng,Zhao, Quan,Zeng, Yanping,Xie, Zhicheng,Xie, Xin,Lu, Boxun,Hu, Youhong
, p. 941 - 957 (2020/11/30)
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.
MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
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Paragraph 0092, (2014/10/04)
Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
Secondary metabolites from the Gorgonian Echinomuraceae splendens (Thomson & Simson)
Parameswaran,Naik,Govenkar
, p. 1093 - 1096 (2007/10/03)
Two xanthine derivatives, caffeine (1, 3, 7-trimethylxanthine) 1 and its 2-O-methyl analog (Δ1, O2- methyl theobromine) 2, N-methyl-pyrazole-5-carboxylic acid 3 and a tetrahydroxy sterol, 1β, 3β, 5α, 6β-tetrahydroxycholestane 4 have been isolated from the methanol extract of the gorgonian Echinomuraceae spendens (Thomson & Simson). These compounds have been purified on silica gel and Sephadex LH-20 columns and their structures elucidated by spectroscopic studies. This is the first report of the occurrence of compounds 2 and 3 in nature. Caffeine exhibits mild antifouling activity against marine fouling organisms while its O-methyl analog 2 is inactive.