Discovery of a new inhibitor for the yth domain-containing m6a rna readers
AssigneeThe Trustees of Boston College
InventorsHuiqing Zhou, Chuan-Hui Wang
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Abstract
The present invention discloses a method for inhibiting a pan-YTH domain by contacting the pan-YTH domain with a small molecule pan-YTH domain inhibitor. Novel methods of locating the small molecule inhibitors are discussed for high-throughput screening (HTS). The small molecule pan-YTH domain inhibitor is designed to inhibit multiple YTH domains present in a YTH family of proteins that identify m6A-modified transcripts, thereby altering the post-transcriptional modification process.
Claims20
A method for inhibiting a pan-YTH domain by contacting the domain with a small molecule inhibitor comprising Formula 1:
- and/or a pharmaceutically acceptable salt thereof, hydrate and/or solvate thereof, tautomer thereof, and/or a prodrug thereof of Formula 1;
- wherein each independent occurrence of A and/or B is independently selected from and/or comprises one or more of the following substituents and/or a salt, tautomer, hydrate and/or solvate thereof:
- wherein each independent occurrence of is a linker to Formula 1 and represents an attachment to an atom as indicated in Formula 1 and includes or is a combination of a single bond (−), a bond to a nitrogen, a bond to a carbon, a bond to an oxygen (—O—), a double bond (=), a triple bond (≡) or (—C2H2—), a bond to C—C, a bond to C—N, —(CH2)n—, wherein independently each n=0, 1, 2, 3, 4, 5, 6, 7, 8, or 9;
- or a combination thereof.
A method for identifying pan-YTH domain inhibitors, the method comprising the steps of
- (1) contacting an YTH domain of the YTHDF1 protein and FAM-labeled m6A RNA with a candidate inhibitor;
- and
- (2) executing FP HTS (fluorescence polarization, high-throughput screening) on the candidate inhibitor;
- whereby a potential inhibition provided by the candidate is indicated.
A method of treating a disease or disorder, comprising:
- contacting a pan-YTH domain in a subject with a small molecule pan-YTH domain inhibitor, wherein the small molecule pan-YTH domain inhibitor is capable of inhibiting multiple YTH domains found in a YTH family of proteins that recognize m6A-modified transcripts, thereby changing a post-transcriptional modification process.
Dependencies are inferred from the claim text.