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RG-7112

Name: RG-7112
Brand: Selleck Chemicals
SKU: S7030
Rating: 5 (15 reviews)

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.

CAS No. 939981-39-2

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

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Mdm2 Signaling Pathway Map

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 (K_D 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=>

Click to View More Cell Line Experimental Data

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

References

[1] Vu B, et al. ACS Med Chem Lett. 2013, 4(5):466-9.

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. Click to purchase: CMC Na	14mg/mL

Chemical Information

Molecular Weight	726.28
Formula	C₃₈H₄₈Cl₂N₄O₄S
CAS No.	939981-39-2
Storage	3 years	-20°C	powder
Storage	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

Download RG-7112 SDF

In vivo Formulation Calculator (Clear solution)

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

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

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.)

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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.

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Molarity Calculator

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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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