TP-020

Protein target name:

MGAT2

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

up to 1 uM

Probe Availability

Freely available from SGC Donated Chemical Probes

Probe Information

Target and Probe Information

Target Details

Target class:

GNT2; CDG2A; CDGS2; GNT-II; GLCNACTII

Probe Details

Chemical Probes Portal ID:

CPP1883

ChEMBL ID:

CHEMBL4455357

SMILES string:

Cn1c(cc(C(F)(F)F)n1)c1cnc(nc1)N1CCc2cc(cc(c12)N1CCCC1=O)S(Nc1c(cc(cc1F)[Cl])F)(=O)=O

InChi Key:

VSZRYLHBOKTNBO-UHFFFAOYSA-N

Control compound:

TP-020n

Physico-chemical properties

NMR:

1H NMR (500 MHz, DMSO-d6) δ 10.05 (s, 1H), 8.82 (s, 2H), 7.55 (d, J = 1.9 Hz, 1H), 7.53 – 7.50 (m, 1H), 7.47 – 7.36, (m, 2H), |3J (C, F)|: = 7.43, 7.09 – 7.02 (m, 1H), 4.40 (t, J = 8.2 Hz, 2H), 3.97 (s, 3H), 3.86 (t, J = 4.0 Hz, 2H), 3.20 (t, J = 8.1 Hz, 2H), 2.03 (d, J = 3.6 Hz, 4H)

13C NMR (126 MHz, DMSO-d6) δ 171.18, |1J (C, F)|: = 160.40, 158.40, |3J (C, F)|: = 160.47, 160.43, 158.46, 158,41|, 159.99, 159.95, 157.98, 157.93, 157.50, 156.98, 140.65, 139.61, 139.49, 137.57, 134.47, 132.76, |1J (C, F)|: = 127.49-125.32125.16, 123.03, 120.90, 118.77|, 125.91, 124.05, 120.24, 114.79, 113.50, 113.29, 112.81, 104.97, 104.95, 51.81, 48.50, 38.29, 31.26, 30.27, 27.52, 17.92

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

7.8 nM (human) 2.4 nM (Mouse)

Potency assay:

Enzymatic Assay

Off target activity

Potency (off target):

IC50

Off target protein and potency:

MGAT1 2.6 uMDGAT1 >30 uMDGAT2 >30 uM ACAT1 19 uM

In cell validation

On target activity in cells

Potency in cells:

IC50

160 nM

Potency assay (cells):

Cell Based Assay

Off target activity in cells

Probe Selectivity in Cell:

KinomeSCAN and GPCR scan available from SGC

Toxicity

Cytoxicity assay:

Yes

Notes on cytotoxicity:

30 uM 80%

In vivo validation

Organism:

Male C57BL/6J mice

Dose:

0.1-1-3-10-30 mg/Kg

Route of delivery:

Oral

Systemic clearance:

205 mL/h/kg

Primary Reference

Reference (doi):

10.1371/journal.pone.0150976 0.1016/j.bmc.2015.06.003

Reference (PMID):

26938273 26100443

External Resources

Available data:

SGC additional compound analysis

Under Review

This probe is in the process of SAB review. Please continue to check back for new reviews and commentary.

Part of the Donated Chemical Probes initiative from SGC.

SAB Rating

Rating for use in Cells

1 review(s)

Rating for use in Model Organisms

1 review(s)

SAB Members

SAB Comments

Probe molecule was evaluated against MGAT2 in vitro, but not in cells. Evaluated against recombinant preparations of DGAT1, DGAT2 and ACAT1 shows selectivity for MGAT2. No data shown for other MGAT isoforms. Not enough off-target or in cell validation performed to fully evaluate selectivity in original publication. Probe shown to inhibit triglyceride production at various concentrations (1–30 mg/kg) in mice. Use with appropriate controls.

Sep 24 2020 - 11:10am

TP-020

Probe Availability

Probe Information

Target Details

GNT2; CDG2A; CDGS2; GNT-II; GLCNACTII

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Toxicity

In vivo validation

Primary Reference

External Resources

Supporting Organizations

Interested in supporting the portal?

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TP-020

Probe Availability

Probe Information

Target Details

GNT2; CDG2A; CDGS2; GNT-II; GLCNACTII

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

Toxicity

In vivo validation

Primary Reference

External Resources

Supporting Organizations

Interested in supporting the portal?