Small-molecule inhibitors of METTL3, the major human epitranscriptomic writer
| Title | Small-molecule inhibitors of METTL3, the major human epitranscriptomic writer |
| Publication Type | Journal Article |
| Year of Publication | 2020 |
| Authors | Bedi R.K, Huang D., Eberle S.A, Wiedmer L., Śledź P., Caflisch A. |
| Journal | ChemMedChem |
| Volume | 15 |
| Issue | 9 |
| Pagination | 744-748 |
| Date Published | 2020 Mar 11 |
| Type of Article | Research Article |
| Keywords | epitranscriptomics, m6A writer, small molecule binding, Virtual Screening, X-ray crystallography |
| Abstract | The RNA methylase METTL3 catalyzes the transfer of a methyl group from the cofactor S-adenosyl-L-methionine (SAM) to the N6 atom of adenine. We have screened a library of 4000 analogues and derivatives of the adenosine moiety of SAM by high-throughput docking into METTL3. Two series of adenine derivatives were identified in silico, and the binding mode of six of the predicted inhibitors was validated by protein crystallography. Two compounds, one for each series, show good ligand efficiency. We propose a route for their further development into potent and selective inhibitors of METTL3. |
| DOI | 10.1002/cmdc.202000011 |
| pubindex | 0253 |
| Alternate Journal | ChemMedChem |
| PubMed ID | 32159918 |
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