SGC707

Reagent Authentication Certificate:

Chemical Probes Portal SGC707.pdf

Protein target name:

PRMT3

Mechanism of action:

Allosteric Inhibitor

Recommended Concentration for use in cells:

10 nM - 10 uM

Probe Availability

Tocris (SGC 707)

MedChem Express (1687736-54-4)

MilliporeSigma (SGC707)

Cayman (1687736-54-4)

Probe Information

Target and Probe Information

Target Details

Target class:

Epigenetics

Subclass:

Protein methyltransferase

HUGO ID:

HGNC:30163

Entrez gene ID:

10196

UNIPROT ID:

O60678

Target alias:

HRMT1L3

Probe Details

Chemical Probes Portal ID:

CPP55

Probe alias:

GTPL8552, AOB5757, SGC 707

PubChem CID:

90642938

SMILES string:

C1CCN(C1)C(=O)CNC(=O)NC2=CC3=C(C=C2)C=NC=C3

InChi Key:

DMIDPTCQPIJYFE-UHFFFAOYSA-N

Control compound:

XY1

Orthogonal probe:

MS023

PAINs evaluation:

PAINs free

Physico-chemical properties

Solubility - preferred solvent:

DMSO

Solubility - concentration:

100 mM

NMR:

1H NMR (600 MHz, Methanol-d4) δ 9.03 (s, 1H), 8.29 (d, J = 5.9 Hz, 1H), 8.10 (d, J = 2.1 Hz, 1H), 7.98 (d, J = 8.9 Hz, 1H), 7.65 (d, J = 6.0 Hz, 1H), 7.59 (dd, J = 8.9, 2.0 Hz, 1H), 4.06 (s, 2H), 3.53 (t, J = 6.8 Hz, 2H), 3.48 (t, J = 6.9 Hz, 2H), 2.03 (app p, J = 6.8 Hz, 2H), 1.91 (app p, J = 6.9 Hz, 2H).

13C NMR (151 MHz, Methanol-d4) δ 169.64, 157.55, 152.18, 143.67, 142.90, 138.81, 129.87, 126.23, 122.27, 121.72, 112.41, 47.19, 46.72, 43.22, 26.94, 25.09.

Storage Recommendations

Storage (solution):

-20 oC 2 years

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

53 nM

Potency assay:

ITC; 85 nM by SPR IC50 = 31 nM in Scintillation proximity assay, and 66 nM in LC-MS detection assay under balanced conditions.

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

4RYL

Structure-activity relationship:

Yes

Off target activity

Potency assay (off target):

Selective for PRMT3 over 31 DNA, RNA and protein methyltransferases.

Probe Selectivity in Vitro:

Selective for PRMT3 over 250 kinases, GPCRs, ion channels and transporters. Modest off-target activity was noted at 10,000 nM SGC707: 69% inhibition of HTR2B (Ki > 15,000 nM); 56% inhibition of BRSK1; 60% inhibition of DLK1; 55% inhibition of RPS6KA4; 58% inhibition of PRKG2, and 61% inhibition of PRKX.

In cell validation

On target activity in cells

Potency in cells:

EC50

1.3 uM

Potency assay (cells):

In CELL Hunter Assay in HEK293 cells, and IC50 = 225 nM in a cellular protein substrate methylation assay.

Target engagement assay (cells):

Direct: In CELL Hunter Assay

Toxicity

Cytoxicity assay:

Yes

Notes on cytotoxicity:

Cytotoxicity noted at high concentration (50 or 100 uM) in 293, LnCap, U2OS, HFF, MCF-7, and MDA-MB231 cells.

In vivo validation

Organism:

CD1 mouse

Dose:

30 mg/mL

Route of delivery:

Intraperitoneal

Cmax:

38000 nM

Primary Reference

Reference (doi):

10.1002/anie.201412154

Reference (PMID):

25728001

SGC707

Probe Availability

Probe Information

Target Details

HRMT1L3

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Toxicity

In vivo validation

Primary Reference

Supporting Organizations

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SGC707

Probe Availability

Probe Information

Target Details

HRMT1L3

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Toxicity

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?