MS023

Noncompetitive inhibitor of PRMT1, PRMT6, CARM1, PRMT8, PRMT3

Structure

Information

Protein target names: PRMT1, PRMT6, CARM1, PRMT8, PRMT3

Mechanism of action: Noncompetitive inhibitor

Recommended in-cell concentration:
5 nM - 2 uM

In Vitro Validations

Uniprot ID: Q99873
Target Class: Epigenetic
Target SubClass: Protein methyltransferase
Potency: Ki
Potency Value: 11 nM
Potency Assay: Potency was quantified in several in vitro assays including scintillation proximity assay and ITC.
PDB ID for probe-target interaction (3D structure): --
Structure-activity relationship: Yes.
Target aliases:
Protein arginine N-methyltransferase 1, IR1B4, HRM ...

DOI Reference: 10.1021/acschembio.5b00839

In Cell Validations

In Vivo Data

No in Vivo Validations

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SERP ratings and comments


SERP Ratings

In Cell Rating

(last updated: 31 May 2016 )

SERP Ratings

In Cell Rating

(last updated: 7 Jun 2016 )

SERP Ratings

In Cell Rating

SERP Comments:

MS023 is a potent and non-selective inhibitor of Type-1 PRMT's and is structurally related to the PRMT6 inhibitor EPZ020411. MS023 binding to PRMT6 has been confirmed using orthogonal assays, including DSF (at high concentrations) and ITC. MS023 does not inhibit a panel of 25 PKMTs (protein lysine methyltransferases), and DNMTs (DNA methyltransferases) and three histone lysine demethylases (IC50<100nM). Inhibition of PRMT1 and PRMT6 with M023 translates to inhibition of asymmetric dimethylation of H4R3 (in MCF7 cells) and H3R2 (in HEK293 cells)(IC50<100nM). Pan-inhibition of Type 1 PRMT's with M023 translates to inhibition of global mono- and asymmetric dimethylation of arginine residues in MCF7 and HEK293 cells. MS023 did not have a major influence in cell viability (8 cell lines) after 96h, at concentrations up to 10µM, except for HEK293 cells. No ADME of physicochemical information on MS023 is available. MS023 (and its inactive analogue MS094) should be used in-cell based assays to interrogate the pharmacological consequences of non-selective PRMT inhibition.

(last updated: 7 Jun 2016 )