MS023

Reagent Authentication Certificate:

Chemical Probes Portal MS023.pdf

Protein target name:

PRMT1, PRMT3, PRMT4, PRMT6, PRMT8

Mechanism of action:

Noncompetitive inhibitor

Recommended Concentration for use in cells:

5 nM - 2 uM

Probe Availability

Tocris (MS 023 dihyrochloride)

MedChem Express (1831110-54-3)

MilliporeSigma (1831110-54-3)

Cayman (MS023 hydrochloride)

Probe Information

Target and Probe Information

Target Details

Target class:

Epigenetics

Subclass:

Protein methyltransferase

HUGO ID:

HGNC:5187 HGNC:30163 HGNC:23393 HGNC:18241 HGNC:5188

Entrez gene ID:

3276 10196 10498 55170 56341

UNIPROT ID:

Q99873 Q96LA8 Q86X55 Q9NR22 O60678

Target alias:

HRMT1L6

Probe Details

Chemical Probes Portal ID:

CPP63

Probe alias:

GTPL8955

PubChem CID:

92136227

SMILES string:

CC(C)OC1=CC=C(C=C1)C2=CNC=C2CN(C)CCN

InChi Key:

FMTVWAGUJRUAKE-UHFFFAOYSA-N

Control compound:

MS094

Orthogonal probe:

EPZ020411SGC707

PAINs evaluation:

PAINs free

Physico-chemical properties

NMR:

1H NMR (600 MHz, CDCl3): δ 7.88 (s, 1H), 7.38 (d, J = 8.6 Hz, 2H), 7.18 (s, 1H), 6.89 (d, J = 8.6 Hz, 2H), 4.57 (hept, J = 5.9 Hz, 1H), 3.76 (s, 3H), 1.62 (s, 9H), 1.35 (d, J = 6.1 Hz, 6H)

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

PRMT6: 0.8 nM, PRMT 1: 11 nM

Potency assay:

Potency was quantified in several in vitro assays including scintillation proximity assay and ITC. Kis for the remaining type I PRMTs were: PRMT3 55 nM, PRMT4 23 nM, PRMT8 1.3 nM. In the ITC assay, MS023 bound PRMT6 with a KD = 6 nM.

PDB ID for probe-target interaction (3D structure):

5E8R

Structure-activity relationship:

Yes.

Off target activity

Potency assay (off target):

No activity was detected against 25 PKMTs, DNMT or Lysine demethylases up to 10 uM.

Probe Selectivity in Vitro:

No binding activity was detected against 9 methyllysine or methylarginine reader proteins in DSF or differential static light scattering assays up to 10 uM.

In cell validation

On target activity in cells

Potency in cells:

IC50

PRMT1: 9 nM, PRMT6: 56 nM

Potency assay (cells):

Methylation of PRMT1 protein substrate in MCF7 cells, and methylation of PRMT6 protein substrate in PRMT6-overexpressing HEK293 cells.

Target engagement assay (cells):

Indirect, substrate methylation assays described above.

Primary Reference

Reference (doi):

10.1021/acschembio.5b00839

Reference (PMID):

26598975

Endorsed probe

The Chemical Probes Portal endorses this compound as chemical probe for use in cells.

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

no rating

SAB Members

SAB 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.

Feb 19 2020 - 4:00pm

MS023

Probe Availability

Probe Information

Target Details

HRMT1L6

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?

Search form

MS023

Probe Availability

Probe Information

Target Details

HRMT1L6

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?