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RG7112

RG7112 : Antagonist of MDM2

Structure

Information

  • MDM2
  • Antagonist
  • Up to 1 uM

In Vitro Validations

Uniprot ID: Q00987
Target Class: Other post-translational modification
Target SubClass: E3 ubiquitin ligase
Potency: IC50
Potency Value: 0.018 uM
Potency Assay: Homogenous time-resolved fluoresence (HTRF) assay with N-terminal domain from MDM2 and a peptide from the p53 binding site.
PDB ID for probe-target interaction (3D structure): 4IPF
Structure-activity relationship: Yes, see ACS Med Chem paper
Target aliases:
E3 ubiquitin-protein ligase Mdm2, MDM2, MDM2_HUMAN ...

In Cell Validations

In Vivo Data

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SERP ratings and comments

SERP Ratings

In Cell Rating
In Model Organisms

(last updated: 7 Jun 2017 )

SERP Ratings

In Cell Rating
In Model Organisms

SERP Comments:

Public notes can be found at http://www.citeulike.org/user/cdsouthan/article/14369611. Note it will also go live in the Guide to Pharmacology by August 2017 (Ligand 9699).

Configuration of the active enantiomer (4S,5R:  CID 57406853) is critical since it is ~ 200-fold more potent compared with (4R,5S: CID 74889557). There are many vendors included in the PubChem entry, but users are advised to ensure (even by direct QC) that the bottle in fact contains the 4R,5S isomer. Note that Compound 2l with an IC50=2,163 nM could be used as a low activity (quasi negative) control, and Nutlin 3a would also be a useful internal control.

There are 27 matches in PubMed https://www.ncbi.nlm.nih.gov/pubmed/RG7112 so other publications can be consulted to get a full picture before using the probe. I could not find data demonstrating in vitro specificity against paralogues. While the sequence similarity with O15151 MDM4_HUMAN is low at 33% over 490 residues, there are reports of complexing between MDM2 and MDM4.

(last updated: 28 Jun 2017 )