Abstract

Post-transcriptional modifications of RNA have emerged as
important regulators of RNA stability and function, involved in processes such as translation and RNA turnover. Recently, it has been implicated that these modifications and their corresponding enzymes can promote the development and progression of cancer. METTL3 is an RNA methyltransferase which is responsible for the deposition of N-6-methyladenosine (m6A) on mRNA targets such as SP1, to
modulate their stability and expression. METTL3 was identified as an essential gene for the growth of AML cells and proposed as a novel target for cancer therapy (Barbieri 2017). Here we demonstrate the in vitro and in vivo characterization of novel small molecule inhibitors of METTL3, which summarise the genetic validation of METTL3 as a novel cancer target, using a pharmacological audit trail.