NCIt definition : A small molecule inhibitor of histone methyltransferase with potential antineoplastic
activity. Upon intravenous administration, pinometostat specifically blocks the activity
of the histone lysine-methyltransferase DOT1L, thereby inhibiting the methylation
of nucleosomal histone H3 on lysine 79 (H3K79) that is bound to the mixed lineage
leukemia (MLL) fusion protein which targets genes and blocks the expression of leukemogenic
genes. This eventually leads to an induction of apoptosis in the leukemic cells bearing
the MLL gene translocations. DOT1L, a non-SET domain-containing histone methyltransferase,
specifically methylates H3K79 and plays a key role in normal cell differentiation
and in the development of leukemia with MLL gene rearrangement on chromosome 11 and
promotes the expression of leukemia-causing genes.;
Semantic type(s)