Home Apoptosis MDM2/MDMX inhibitor - p53 inhibitor RG-7112 For research use only.

RG-7112

Synonyms: RO5045337

RG7112 (RO5045337) is an orally bioavailable and selective p53-MDM2 inhibitor with HTRF IC50 of 18 nM.

RG-7112 Chemical Structure

RG-7112 Chemical Structure

CAS No. 939981-39-2

Purity & Quality Control

RG-7112 Related Products

Signaling Pathway

MDM2/MDMX Signaling Pathways

MDM2/MDMX Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
SJSA1 Cytotoxicity assay 5 days Cytotoxicity against human SJSA1 cells expressing wild type p53 assessed as cell viability after 5 days by MTT assay, IC50 = 0.3 μM. 24900694
RKO Cytotoxicity assay 5 days Cytotoxicity against human RKO cells expressing wild type p53 assessed as cell viability after 5 days by MTT assay, IC50 = 0.4 μM. 24900694
HCT116 Cytotoxicity assay 5 days Cytotoxicity against human HCT116 cells expressing wild type p53 assessed as cell viability after 5 days by MTT assay, IC50 = 0.5 μM. 24900694
SJSA1 Antiproliferative assay 1 hr Antiproliferative activity against human SJSA1 cells assessed as inhibition of EdU incorporation after 1 hr by Click-iT EdU HCS assay in presence of 10% human serum, IC50 = 0.581 μM. 24456472
SJSA1 Cytotoxicity assay 16 hrs Cytotoxicity against human SJSA1 cells assessed as growth inhibition after 16 hrs by EdU incorporation assay in presence of 10% human serum, IC50 = 0.581 μM. 24601644
MDA-MB-435 Cytotoxicity assay 5 days Cytotoxicity against human MDA-MB-435 cells expressing p53 mutant assessed as cell viability after 5 days by MTT assay, IC50 = 9.9 μM. 24900694
SW480 Cytotoxicity assay 5 days Cytotoxicity against human SW480 cells expressing p53 mutant assessed as cell viability after 5 days by MTT assay, IC50 = 16.6 μM. 24900694
Click to View More Cell Line Experimental Data

Biological Activity

Description RG7112 (RO5045337) is an orally bioavailable and selective p53-MDM2 inhibitor with HTRF IC50 of 18 nM.
Targets
MDM2 [1]
(Cell-free assay)		 p53-MDM2 interaction [1]
(Cell-free assay)
11 nM(Kd) 18 nM
In vitro
In vitro RG7112 is a potent and selective member of the nutlin family of MDM2 antagonists currently in phase I clinical studies. RG7112 binds MDM2 with high affinity (KD of 10.7 nM), blocking its interactions with p53 in vitro. A crystal structure of the RG7112–MDM2 complex reveals that the small molecule binds in the p53 pocket of MDM2, mimicking the interactions of critical p53 amino acid residues. Treatment of cancer cells expressing wild-type p53 with RG7112 activates the p53 pathway, leading to cell-cycle arrest and apoptosis. RG7112 shows potent antitumor activity against a panel of solid tumor cell lines. However, its apoptotic activity varies widely with the best response observed in osteosarcoma cells with MDM2 gene amplification. [1]
Experimental Result Images Methods Biomarkers Images PMID
Western blot MDM2 / PARP / Cleaved PARP p-TP53 / PUMA / Survivin 30022047
Immunofluorescence p53 / p21 30022047
Growth inhibition assay Cell viability 30022047
In Vivo
In vivo RG7112 activates p53 pathway and induces apoptosis in tumor cells in vivo. Oral administration of RG7112 to human xenograft-bearing mice at nontoxic concentrations caused dose-dependent changes in proliferation/apoptosis biomarkers as well as tumor inhibition and regression. Notably, RG7112 is highly synergistic with androgen deprivation in LNCaP xenograft tumors. [1]
Animal Research Animal Models SJSA-1, SJSA-1luc2, and MHM xenografted Balb/c nude mice
Dosages 25–200 mg/kg
Administration oral

Chemical Information & Solubility

Molecular Weight 726.28 Formula

C38H48Cl2N4O4S
CAS No. 939981-39-2 SDF Download RG-7112 SDF
Smiles CCOC1=C(C=CC(=C1)C(C)(C)C)C2=NC(C(N2C(=O)N3CCN(CC3)CCCS(=O)(=O)C)(C)C4=CC=C(C=C4)Cl)(C)C5=CC=C(C=C5)Cl
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (137.68 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble


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In vivo
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In vivo Formulation Calculator

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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