Abstract / Summary
SETD2 is a histone methyltransferase and is the only enzyme known to be capable of trimethylation of histone 3 lysine 36 (H3K36me2 → H3K36me3). SETD2 can also methylate non-histone proteins and is important in transcriptional regulation, RNA splicing, DNA damage repair and B cell development and differentiation [ 1 , 2 ]. SETD2 inhibition has been shown to reduce the proliferation of Multiple Myeloma (MM) and Diffuse Large B-cell Lymphoma (DLBCL) cell lines and reduce tumour burden in cell line-derived xenograft models [ 1 ]. The SETD2 inhibitor EZM0414 was initially granted fast-track FDA designation and investigated in a phase 1 clinical trial in patients with relapsed/refractory MM and DLBCL (NCT05121103), but this study terminated early due to business decisions.