RG-7112

Catalog No.S7030 Synonyms: RO5045337

For research use only.

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

RG-7112 Chemical Structure

CAS No. 939981-39-2

Selleck's RG-7112 has been cited by 15 publications

Purity & Quality Control

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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 [1]
(Cell-free assay)
11 nM(Kd) 18 nM
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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
SJSA1 NEThSItEgXSxdH;4bYNqfHliYYPzZZk> NEHmcWU2KGSjeYO= NHHpOIFEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBUUlODMTDj[YxteyCneIDy[ZN{cW6pIIfpcIQhfHmyZTDwOVMh[XO|ZYPz[YQh[XNiY3XscEB3cWGkaXzpeJkh[W[2ZYKgOUBl[Xm|IHL5JG1VXCCjc4PhfUwhUUN3MDC9JFAvOyEQvF2u NFfvTWE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwNFY6PCd-MkS5NFA3QTR:L3G+
RKO M1r1ZmN6fG:2b4jpZ4l1gSCjc4PhfS=> M4LQN|Uh\GG7cx?= MkfvR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gVmtQKGOnbHzzJIV5eHKnc4Ppcochf2muZDD0fZBmKHB3MzDhd5Nme3OnZDDhd{Bk\WyuII\pZYJqdGm2eTDh[pRmeiB3IHThfZMh[nliTWTUJIF{e2G7LDDJR|UxKD1iMD60JO69VS5? M3W0S|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUCwOlk1Lz5{NEmwNFY6PDxxYU6=
HCT116 NFvuNmpEgXSxdH;4bYNqfHliYYPzZZk> MlTaOUBl[Xm| MYDDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDIR3QyOTZiY3XscJMh\XiycnXzd4lv\yC5aXzkJJR6eGVicEWzJIF{e2W|c3XkJIF{KGOnbHygeoli[mmuaYT5JIFnfGW{IEWg[IF6eyCkeTDNWHQh[XO|YYmsJGlEPTBiPTCwMlUh|ryPLh?= NE\JZYc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwNFY6PCd-MkS5NFA3QTR:L3G+
SJSA1 NXm4[pFNSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= NF7DfHEyKGi{ NXjvNIp2SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDTTnNCOSClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGVlXSCrbnPvdpBwemG2aX;uJIFnfGW{IEGgbJIh[nliQ3zpZ4sucVRiRXTVJGhEWyCjc4PhfUBqdiCycnXz[Y5k\SCxZjCxNEUhcHWvYX6gd4VzfW1uIFnDOVAhRSByLkW4NUDPxE1w MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDR3NkS3Nkc,OjR2NU[0O|I9N2F-
SJSA1 NYnnSIRnS3m2b4TvfIlkcXS7IHHzd4F6 MnvVNVYhcHK| NWnPXW9LS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hW0qVQUGgZ4VtdHNiYYPz[ZN{\WRiYYOg[5Jwf3SqIHnubIljcXSrb36gZYZ1\XJiMU[gbJJ{KGK7IFXkWUBqdmOxcoDvdoF1cW:wIHHzd4F6KGmwIIDy[ZNmdmOnIH;mJFExLSCqdX3hckB{\XK3bTygTWM2OCB;IECuOVgyKM7:TT6= M13sdlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NkCxOlQ1Lz5{NE[wNVY1PDxxYU6=
MDA-MB-435 MmLnR5l1d3SxeHnjbZR6KGG|c3H5 NHr1OVg2KGSjeYO= NHjRe4tEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBOTEFvTVKtOFM2KGOnbHzzJIV5eHKnc4PpcocheDV|IH31eIFvfCCjc4Pld5Nm\CCjczDj[YxtKH[rYXLpcIl1gSCjZoTldkA2KGSjeYOgZpkhVVSWIHHzd4F6NCCLQ{WwJF0hQS57IN88UU4> NEf0N4s9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwNFY6PCd-MkS5NFA3QTR:L3G+
SW480 MYLDfZRwfG:6aXPpeJkh[XO|YYm= NYrqPYp1PSCmYYnz Mkf0R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV3c1QDBiY3XscJMh\XiycnXzd4lv\yCyNUOgcZV1[W62IHHzd4V{e2WmIHHzJINmdGxidnnhZoltcXS7IHHmeIVzKDViZHH5d{BjgSCPVGSgZZN{[XluIFnDOVAhRSBzNj62JO69VS5? NYHSeHVbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFA3QTRpPkK0PVAxPjl2PD;hQi=>
Assay
Methods Test Index PMID
Western blot MDM2 / PARP / Cleaved PARP ; p-TP53 / PUMA / Survivin 30022047 27659536
Immunofluorescence p53 / p21 30022047
Growth inhibition assay Cell viability 30022047
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]

Protocol (from reference)

Animal Research:

[1]

  • Animal Models: SJSA-1, SJSA-1luc2, and MHM xenografted Balb/c nude mice
  • Dosages: 25–200 mg/kg
  • Administration: oral

Solubility (25°C)

In vitro

DMSO 100 mg/mL
(137.68 mM)
Ethanol 100 mg/mL
(137.68 mM)
Water Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
1% CMC Na
For best results, use promptly after mixing.

14mg/mL

Chemical Information

Molecular Weight 726.28
Formula

C38H48Cl2N4O4S

CAS No. 939981-39-2
Storage 3 years -20°C powder
2 years -80°C in solvent
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

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

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.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

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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