AZD3988

Protein target name:

DGAT1

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

up to 100 nM

Probe Availability

TOCRIS

MedChemExpress

Probe Information

Target and Probe Information

Target Details

Target class:

Other

Define other target class:

Metabolic Enzyme

Subclass:

Diacylglycerol O-acyltransferase

HUGO ID:

HGNC:2843

Entrez gene ID:

8694

UNIPROT ID:

O75907

Target alias:

ARAT; DGAT; ARGP1; DIAR7

Probe Details

Chemical Probes Portal ID:

CPP2063

Probe alias:

cpd 53

PubChem CID:

23648867

ChEMBL ID:

CHEMBL2036730

SMILES string:

O=C(NC3=CC=[C@@]([C@H]4CC[C@H](CC(O)=O)CC4)C=C3)C1=NN=C(NC2=CC(F)=C(F)C=C2)O1

InChi Key:

NGEBYTLALFOQKI-UHFFFAOYSA-N

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

0.6 (H), 0.5 (R), 1.1 (M) nM

Potency assay:

Enzymatic activity

Structure-activity relationship:

yes

Off target activity

Potency (off target):

IC50

Off target protein and potency:

ACAT1 86 nMACAT2 600 nM

Potency assay (off target):

Enzymatic Activity

Probe Selectivity in Vitro:

no significant activity against DGAT-2, the hERG encoded potassium channel (>30 μM), and cytochrome P450 enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 (all >30 μM)

In cell validation

On target activity in cells

Potency in cells:

IC50

0.5 nM

Potency assay (cells):

Inhibition of triacylglycerol (TAG) synthesis

In vivo validation

Organism:

Mouse, Rat, Dog

Dose:

0.5 (M), 2 (R), 1 (D) mg/kg IV, 1 (M), 5 (R), 1 (D) mg/kg PO, Reviewer suggest: 20 mg/Kg (M), 0.5-5 mg/Kg (R)

Route of delivery:

OralIntravenous

Plasma half life:

4.9 (M), 3.4 (R), 1.8 (D) h (IV), 4.7 (M), 5.8 (R), 5.7 (D) h (PO)

Systemic clearance:

4.6 (M), 1.1 (R), 2.5 (D) mL/min/kg

Cmax:

1.9 (M), 20 (R), 1.5 (D) uM (PO)

Primary Reference

Reference (doi):

10.1016/j.bmcl.2012.04.117

Reference (PMID):

22608962

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

Overall, AZD3988 has very favourable probe properties to study DGAT-1. The probe shows a clear mechanism of action and engages with the target at low nanomolar concentrations, exhibits selectivity for DGAT-1 over DGAT-2 in vitro in cellulo, and in vivo, and there are no common off-target liabilities observed (hERG, P450s). Additionally, the physicochemical properties are fairly drug-like for a probe molecule: 3 H-bond donors, 8 H-bond acceptors, molecular weight of 456.45 Da, logD = 3.0, 7 rotatable bonds, and a calculated tPSA of 112.38 Å2.

Jan 7 2021 - 11:39am

AZD3988

Probe Availability

Probe Information

Target Details

ARAT; DGAT; ARGP1; DIAR7

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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AZD3988

Probe Availability

Probe Information

Target Details

ARAT; DGAT; ARGP1; DIAR7

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?