RG7388

Protein target name:

MDM2

Mechanism of action:

Antagonist

Recommended Concentration for use in cells:

10-500 nM

Probe Availability

MedChem Express (1229705-06-9)

Abcam (1229705-06-9)

Cayman (1229705-06-9)

Probe Information

Target and Probe Information

Target Details

Target class:

ACTFS, HDMX, hdm3

Probe Details

Chemical Probes Portal ID:

CPP1590

Probe alias:

Idasanutlin; 1229705-06-9; UNII-QSQ883V35U; RG-7388; RO5503781

PubChem CID:

53358942

ChEMBL ID:

CHEMBL2402737

SMILES string:

CC(C)(C)C[C@H]1[C@]([C@H]([C@@H](N1)C(=O)NC2=C(C=C(C=C2)C(=O)O)OC)C3=C(C(=CC=C3)Cl)F)(C#N)C4=C(C=C(C=C4)Cl)F

InChi Key:

TVTXCJFHQKSQQM-LJQIRTBHSA-N

Orthogonal probe:

RO5353AM-6761AMG232

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

6 nM

Potency assay:

Homogenous time-resolved fluorescence binding assay. In Biacore binding assay, KD=9.79 nM.

Structure-activity relationship:

Yes, see J Med Chem paper

In cell validation

On target activity in cells

Potency in cells:

IC50

0.03 uM

Potency assay (cells):

Average from three p53-positive cancer cell lines (SJSA1, RKO, and HCT116) in MTT assay. RG7388 was 344-fold more potent in this assay against p53-positive cells compared with p53-negative cells.

Target engagement assay (cells):

In SJSA1 cells, RG7388 led to dose-dependent accumulation of p53 and expression of p53-dependent genes (p21, MDM2).

In vivo validation

Organism:

Female nude mice

Dose:

50 mg/kg (oral); 5 mg/kg (IV)

Route of delivery:

OralIntravenous

Plasma half life:

1.6 h (IV)

Systemic clearance:

10.3 mL/mg/kg (IV)

Cmax:

9.9 ug/mL

Organ of Interest

Organ (O):

SJSA1 tumor xenograft

Target engagement assay:

Indirect, inhibition of tumor growth.

Primary Reference

Reference (doi):

10.1021/jm400487c

Reference (PMID):

23808545 26998348

Endorsed probe

The Chemical Probes Portal endorses this compound as chemical probe for use in cells and in model organisms.

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

RG7388 is a second-generation inhibitor of the protein-protein interaction that occurs between wild type p53 (a potent tumor suppressor) and the E3 ubiquitin ligase MDM2. High levels of MDM2 are found in several tumor types, resulting in the destruction of p53. Inhibition of this interaction with chemical probes such as RG7388 can restore wild-type p53 activity in cells. Medicinal chemistry efforts to improve the original 'Nutlin' class of MDM2 inhibitors have yield compounds such as RG7388, with improved activity and pharmacokinetic properties.

Aug 18 2017 - 4:28pm

Potent and optimised MDM2-p53 antagonist that entered into clinical trials. In general, there is only very limited data available with regard to the selectivity of this compound. However, in contrast to some other published compounds from this class, RG7738 appears to only exhibit off-target effects on MDR-1 at concentrations of 5 µM.

Nov 16 2020 - 8:25pm

RG7388

Probe Availability

Probe Information

Target Details

ACTFS, HDMX, hdm3

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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RG7388

Probe Availability

Probe Information

Target Details

ACTFS, HDMX, hdm3

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?