METTL-3 inhibitor STC-15

An orally bioavailable methyltransferase-like protein 3 (METTL-3) inhibitor, with potential antineoplastic activity. Upon oral administration, METTL-3 inhibitor STC-15 targets, binds to and blocks the activity of METTL-3, thereby depleting N-6-methyladenosine (m6A) depositions by METTL3 from certain mRNA transcripts. This leads to the formation of double-stranded RNA, the activation of RNA sensors and the upregulation of expression of genes associated with innate immunity, such as interferon (IFN). This causes upregulation of cytokines and the expression of interferon stimulated genes (ISG). This abrogates the METTL-3-mediated inhibition of certain immune cell functions and causes activation of anti-tumor immune responses, primarily the activation of cytotoxic T lymphocytes in the tumor microenvironment (TME). In addition, by depleting m6A depositions by METTL3 on certain mRNA transcripts, STC-15 negatively affects the stability and translation of certain mRNAs leading to a decrease of the expression of certain tumor-associated and anti-apoptotic genes. STC-15 also inhibits the function of leukemia stem cells. METTL-3, an RNA methyltransferase, plays a key role in the initiation and progression of many types of cancer. It is responsible for the deposition of m6A modification on mRNA and long non-coding RNA (lncRNA) targets to regulate their stability, splicing, transport and translation.