AMG232

AMG232 : Competitive inhibitor of MDM2-p53 interaction

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

MDM2

Antagonist, Competitive inhibitor of MDM2-p53 interaction

10-100 nM

Probe Availability:

In Vitro Validations

Uniprot ID: Q00987

Target Class: Other post-translational modification

Target SubClass: E3 ubiquitin ligase

Potency: Kd

Potency Value: 0.045 nM

Potency Assay: Surface plasmon resonance assay

PDB ID for probe-target interaction (3D structure): 4OAS

Structure-activity relationship: Yes, see J Med Chem paper

Target aliases:

E3 ubiquitin-protein ligase Mdm2, MDM2, MDM2_HUMAN ...

DOI Reference: 10.1021/jm401753e

Uniprot ID: Q00987

Target Class: Other post-translational modification

Target SubClass: E3 ubiquitin ligase

Potency: IC50

Potency Value: 0.6 nM

Potency Assay: HTRF assay

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

Target aliases:

E3 ubiquitin-protein ligase Mdm2, MDM2, MDM2_HUMAN ...

DOI Reference: 10.1021/jm401753e

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

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

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This is a potent, competitive inhibitor of the p53-MDM2 interaction. It has been demonstrated to interrupt p53 binding to MDM2 and induce death in SJSA-1 osteosarcoma cells in a p53-dependent manner. It induces p21 expression in SJSA-1 mouse xenograft and is orally available with favorable PK properties.

(last updated: 24 Jul 2017 )

SERP Ratings

In Cell Rating

In Model Organisms

(last updated: 28 Jul 2017 )

SERP Ratings

In Cell Rating

In Model Organisms

(last updated: 11 Nov 2020 )