EPZ015666

EPZ015666 (GSK3235025) is an orally available inhibitor of protein arginine methyltransferase-5 (PRMT5), which is involved in diverse cellular processes, including tumorigenesis, and its overexpression is observed in cell lines and primary patient samples derived from lymphomas, particularly mantle cell lymphoma (MCL).EPZ015666 showed dose-dependent antitumor activity in multiplein vitroandin vivomantle cell lymphoma (MCL) models with treatment of MCL cell lines leading to inhibition of SmD3 me

Protein arginine methyltransferases (PRMTs) target nuclear and cytoplasmic substrates and can alter protein actions and gene expression. PRMT5, which can methylate histones H2A, H3, and H4, ribonucleoproteins, and other proteins, is upregulated in several human cancers, including lymphomas. Moreover, suppression of PRMT5 expression induces lymphoma cell death. EPZ015666 is a potent, orally bioavailable inhibitor of PRMT5 (Ki = 5 nM). It displays more than 20,000-fold selectivity for PRMT5 over other PMTs. EPZ015666 acts by blocking the association of PRMT5 with methylosome protein 50, which is necessary for the formation of an active methyltransferase complex. EPZ015666 (100 mg/kg twice daily) blocks the growth of mantle cell lymphoma Z-138 xenografts, without significant body weight loss, in mice.[Cayman Chemical]

Molecular Weight:383.4
XLogP3:0.8
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:7
Rotatable Bond Count:7
Exact Mass:383.19573968
Monoisotopic Mass:383.19573968
Topological Polar Surface Area:99.6
Heavy Atom Count:28
Complexity:518
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes