Discovery of METTL3 Small Molecule Inhibitors by Virtual Screening of Natural Products.

ABSTRACT: N⁶-Methyladenosine (m⁶A) is the most prevalent mRNA modification in mammalian cells that is mainly catalyzed by the methyltransferase complex of methyltransferase-like 3 and methyltransferase-like 14 (METTL3-METTL14). Many lines of evidence suggest that METTL3 plays important roles in several diseases such as cancers and viral infection. In the present study, 1,042 natural products from commercially available sources were chosen to establish a screening library, and docking-based high-throughput screening was performed to discover potential METTL3 inhibitors. The selected compounds were then further validated by an in vitro methyltransferase inhibition assay in which m⁶A content was determined by LC-MS/MS. A cellular assay of the inhibition of m

SUBMITTER: Du Y 

PROVIDER: S-EPMC9093036 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature