Preferred Label : PRMT5 Inhibitor SKL27969;
NCIt synonyms : Protein Arginine Methyltransferase 5 Inhibitor SKL27969;
NCIt definition : A central nervous system (CNS)-penetrant, orally bioavailable small molecule inhibitor
of protein arginine methyltransferase 5 (PRMT5), with potential antiproliferative
and antineoplastic activities. Upon oral administration, PRMT5 inhibitor SKL27969
selectively binds to PRMT5 and inhibits its function. By inhibiting its methyltransferase
activity, levels of both monomethylated and dimethylated arginine residues in histones
H2A, H3 and H4 are decreased. This modulates the expression of genes involved in several
cellular processes, including cellular proliferation. This may increase the expression
of antiproliferative genes and/or decrease the expression of genes that promote cell
proliferation, which may lead to decreased growth of rapidly proliferating cells,
including cancer cells. PRMT5, a type II methyltransferase that catalyzes the formation
of both omega-N monomethylarginine (MMA) and symmetric dimethylarginine (sDMA) on
histones and a variety of other protein substrates involved in signal transduction
and cellular transcription, is overexpressed in several neoplasms. Elevated levels
are associated with decreased patient survival. Methylthioadenosine phosphorylase
(MTAP) is deleted in certain cancer cells leading to an accumulation of methylthioadenosine
(MTA). As MTA inhibits PRMT5, MTAP-null cancer cells are specifically sensitive to
PRMT5 inhibitors.;
Molecule name : SKL 27969; SKL-27969;
NCI Metathesaurus CUI : CL1907328;
Origin ID : C200044;
concept_is_in_subset
- has_target
