AMG232

Protein target name:

MDM2

Mechanism of action:

AntagonistCompetitive inhibitor of MDM2-p53 interaction

Recommended Concentration for use in cells:

10-100 nM

Probe Availability

MedChem Express (1352066-68-2)

Probe Information

Target and Probe Information

Target Details

Target class:

ACTFS, HDMX, hdm5

Probe Details

Chemical Probes Portal ID:

CPP1592

Probe alias:

AMG 232; AMG-232

PubChem CID:

58573469

ChEMBL ID:

CHEMBL3125702

SMILES string:

CC(C)[C@@H](CS(=O)(=O)C(C)C)N1[C@@H]([C@H](C[C@](C1=O)(C)CC(=O)O)C2=CC(=CC=C2)Cl)C3=CC=C(C=C3)Cl

InChi Key:

DRLCSJFKKILATL-YWCVFVGNSA-N

Orthogonal probe:

RO5353MI-77301AM-6761

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

0.045 nM

Potency assay:

Surface plasmon resonance assay. In HTRF assay, IC50=0.6 nM.

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

4OAS

Structure-activity relationship:

Yes, see J Med Chem paper

Off target activity

Probe Selectivity in Vitro:

AMG232 showed minimal activity in CYP3A4-inhibition assay and PXR-induction assay.

In cell validation

On target activity in cells

Potency in cells:

IC50

9.1 nM

Potency assay (cells):

In SJSA-1 EdU proliferation assay. In HCT-116 cells, AMG232 selectively inhibited the proliferation of p53 wild-type cells (IC50=10 nM compared with >25 uM for mutant p53 cells).

Target engagement assay (cells):

Indirect, selective inhibition of p53 wild-type HCT-116 cells

In vivo validation

Organism:

RatAthymic, nude mice

Dose:

0.5 mg/kg (rat)

Route of delivery:

IntravenousSubcutaneous

Plasma half life:

2.4 h

Systemic clearance:

0.66 L/h/kg

Organ of Interest

Organ (O):

SJSA-1 xenograft

Target engagement assay:

AMG232 dose-dependently increased p21 RNA in xenografts.

Primary Reference

Reference (doi):

10.1021/jm401753e

Reference (PMID):

24456472

AMG232

Probe Availability

Probe Information

Target Details

ACTFS, HDMX, hdm5

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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AMG232

Probe Availability

Probe Information

Target Details

ACTFS, HDMX, hdm5

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?