AZD3988

Inhibitor of DGAT1

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(3 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Information

DGAT1

Inhibitor

up to 100 nM

Probe Availability:

In Vitro Validations

Uniprot ID: O75907

Target Class: Other

Target SubClass: Diacylglycerol O-acyltransferase

Potency: IC50

Potency Value: 0.6 nM

Potency Assay: Enzymatic activity for human homolog

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

Structure-activity relationship: yes

Target aliases:

Diacylglycerol O-acyltransferase 1, DGAT, AGRP1, D ...

DOI Reference: 10.1016/j.bmcl.2012.04.117

Uniprot ID: O75907

Target Class: Other

Target SubClass: Diacylglycerol O-acyltransferase

Potency: IC50

Potency Value: 0.5 nM

Potency Assay: Enzymatic activity for rat homolog

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

Target aliases:

Diacylglycerol O-acyltransferase 1, DGAT, AGRP1, D ...

DOI Reference: 10.1016/j.bmcl.2012.04.117

Uniprot ID: O75907

Target Class: Other

Target SubClass: Diacylglycerol O-acyltransferase

Potency: IC50

Potency Value: 1.1 nM

Potency Assay: Enzymatic activity for mouse homolog

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

Target aliases:

Diacylglycerol O-acyltransferase 1, DGAT, AGRP1, D ...

DOI Reference: 10.1016/j.bmcl.2012.04.117

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency end-point : IC50 ACAT1 86 nM, ACAT2 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)

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

(last updated: 18 Dec 2020 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP 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.

(last updated: 7 Jan 2021 )

SERP Ratings

In Cell Rating

In Model Organisms

(last updated: 18 Feb 2021 )