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Pharmacophore-based screening of diamidine small molecule inhibitors for protein arginine methyltransferases

Kun Qian, Chunli Yan, Hairui Su, Tran Dang, Bo Zhou, Zhenyu Wang, Xinyang Zhao, Ivaylo Ivanov, Meng‐Chiao Ho, Y. George Zheng

2020RSC Medicinal Chemistry13 citationsDOIOpen Access PDF

Abstract

of 2.6 μM for human PRMT1. Limited selectivity was observed over some other PRMT isoforms such as CARM1 and PRMT7. Molecular modeling and inhibition pattern studies suggest that K313 is a nonclassic noncompetitive inhibitor to PRMT1. K313 significantly inhibited cell proliferation and reduced the arginine asymmetric dimethylation level in the leukaemia cancer cells.

Topics & Concepts

PharmacophoreProtein arginine methyltransferase 5MethyltransferaseVirtual screeningArginineIC50MethylationSmall moleculeBiochemistryChemistryIndole testEnzymeEpigeneticsPharmacologyBiologyIn vitroAmino acidGeneCancer-related gene regulationEpigenetics and DNA Methylation