MI-77301

Antagonist of MDM2

Structure

Information

  • MDM2
  • Antagonist
  • 1-10 uM

In Vitro Validations

Uniprot ID: Q00987
Target Class: Other post-translational modification
Target SubClass: E3 ubiquitin ligase
Potency: Ki
Potency Value: 0.88 nM
Potency Assay: Fluorescence polarization binding assay with MDM2 protein and p53 peptide.
PDB ID for probe-target interaction (3D structure): --
Target aliases:
E3 ubiquitin-protein ligase Mdm2, MDM2, MDM2_HUMAN ...

DOI Reference: 10.1158/0008-5472.CAN-14-0799

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): At 10 uM, MI-77301 did not bind MDMx as assessed by biolayer interferometry.
Probe Selectivity in Vitro:

At 10 uM, MI-77301 showed minimal interaction with BCL2, BCLXL, MCL1, beta-catenin and minimal activity against another ~200 enzymes and proteins.

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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

MI-77301 (synonym SAR405838) is a highly potent and selective MDM2 inhibitor (Ki=0.88 nM). MI-77301 inhibits the cell growth of cancer cell lines like p53 wild-type osteosarcoma SJSA-1 cell line (IC50=92 nM). The in vivo efficacy of the compound was shown in particular in the SJSA-1 osteosarcoma xenograft model.

(last updated: 8 Aug 2017 )

SERP Ratings

In Cell Rating
In Model Organisms

(last updated: 18 Aug 2017 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

This probe is the result of extensive chemistry optimization over the last 10 years. The original compound was a rationally designed inhibitor of the interaction between p53 and MDM2, but it had liabilities that prevented clinical development. This latest compound appears to be outstanding in both cells and a variety of mouse xenograft cancer models.

(last updated: 18 Aug 2017 )

SERP Ratings

In Cell Rating
In Model Organisms

(last updated: 29 Apr 2019 )