The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.
The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.
Patent No.:
Date of Patent:
Jul. 03, 2018
Filed:
Jan. 23, 2017
The Scripps Research Institute, La Jolla, CA (US);
Matthew D. Disney, Jupiter, FL (US);
Biao Liu, East Amherst, NY (US);
Jessica L. Childs-Disney, Jupiter, FL (US);
Wang-Yong Yang, Palm Beach Gardens, FL (US);
The Scripps Research Institute, La Jolla, CA (US);
Abstract
The invention provides a series of bioactive small molecules that target expanded r(CGG) repeats, termed r(CGG), that causes Fragile X-associated Tremor Ataxia Syndrome (FXTAS). The compound was identified by using information on the chemotypes and RNA motifs that interact. Specifically, 9-hydroxy-5,11-dimethyl-2-(2-(piperidin-1-yl)ethyl)-6H-pyrido[4,3-b]carbazol-2-ium, binds the 5'CG/3′GC motifs in r(CGG)and disrupts a toxic r(CGG)-protein complex. Specifically, dimeric compounds incorporating two 9-hydroxyellipticine analog structures can even more potently bind the 5′CG/3′GC motifs in r(CGG)and disrupts a toxic r(CGG)-protein complex. Structure-activity relationships (SAR) studies determined that the alkylated pyridyl and phenolic side chains are important chemotypes that drive molecular recognition of r(CGG) repeats, such as r(CGG). Importantly, the compound is efficacious in FXTAS model cellular systems as evidenced by its ability to improve FXTAS-associated pre-mRNA splicing defects and to reduce the size and number of r(CGG)-protein aggregates.