RG-7112

Name: RG-7112
Brand: Selleck Chemicals
SKU: S7030
Rating: 5 (8 reviews)

For research use only.

Catalog No.S7030 Synonyms: RO5045337

8 publications

CAS No. 939981-39-2

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

Selleck's RG-7112 has been cited by 8 publications

Nat Biotechnol, 2016, 34(11):1161-1167

PubMed: 27723727 ( click the link to review the publication )

Eur J Cancer, 2020, 126:93-103

PubMed: 31927215 ( click the link to review the publication )

Hum Cell, 2020, 10.1007/s13577-020-00420-z

PubMed: 32870449 ( click the link to review the publication )

Elife, 2020, 9:e54693

PubMed: 32821059 ( click the link to review the publication )

Nat Commun, 2019, 10(1):2189

PubMed: 31097698 ( click the link to review the publication )

Cancer Biother Radiopharm, 2019, 34(4):252-257

PubMed: 30724592 ( click the link to review the publication )

Nat Commun, 2018, 9(1):2024

PubMed: 29789628 ( click the link to review the publication )

Oncotarget, 2016, 7(43):70623-70638

PubMed: 27661115 ( click the link to review the publication )

Purity & Quality Control

Choose Selective Mdm2 Inhibitors

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]

Assay

Methods	Test Index	PMID
Western blot	MDM2 / PARP / Cleaved PARP; PubMed: 30022047 Cell Death Dis U138MG, LN18, and A1207 cells were treated with RG7112 for 12 h at the indicated concentrations. p21, MDM2, p53, and PARP levels were examined by immunoblotting. Actin was used as a loading control. p-TP53 / PUMA / Survivin ; PubMed: 27659536 Oncotarget Induction of TP53 phosphorylation and TP53 target proteins (TP21 and PUMA), as determined by western blotting. Cleaved PARP and survivin were also assessed to detect proapoptotic signaling	30022047 27659536
Immunofluorescence	p53 / p21; PubMed: 30022047 Cell Death Dis An image-based immunofluorescence assay for p21 (green), p53 (red) and DAPI (blue) in A1207 cells treated with DMSO, RG7112 (2 μM), AMG232 (2 μM), and Camptothecin (10 μM) for 72 h are shown.	30022047
Growth inhibition assay	Cell viability; PubMed: 30022047 Cell Death Dis Cell numbers of U373MG, LN18, U251MG, A1207, DBTRG-05MG, and U87MG cells treated with different concentrations (0.07–54 μM) of RG7112.	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

Animal Research: ^[1]	- Collapse Animal Models: SJSA-1, SJSA-1luc2, and MHM xenografted Balb/c nude mice Dosages: 25–200 mg/kg Administration: oral (Only for Reference)

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.	14mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download RG-7112 SDF

Molecular Weight	726.28
Formula	C₃₈H₄₈Cl₂N₄O₄S
CAS No.	939981-39-2
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	RO5045337
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)

Dosage

mg/kg

Average weight of animals

Dosing volume per animal

Number of animals

Step 2: Enter the in vivo formulation (Different batches have different solubility ratios, please contact Selleck to provide you with the correct ratio)

% DMSO+ % + % Tween 80+ % ddH₂O

Calculate Reset

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.

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.

Bio Calculators

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration _(start) x Volume _(start) = Concentration _(final) x Volume _(final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

Serial Dilutions
Concertration (start):
Dilution-folds:

Computed Result

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

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

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

Mdm2 Signaling Pathway Map

Related Mdm2 Products

Idasanutlin (RG-7388) ^New

Idasanutlin (RG-7388) is a potent and selective p53-MDM2 inhibitor with IC50 of 6 nM showing improved in vitro binding as well as cellular potency/selectivity.
MI-773 (SAR405838) ^New

MI-773 (SAR405838) is an orally available MDM2 antagonist with K_i of 0.88 nM. Phase 1.
A-1210477 ^New

A-1210477 is a potent and selective MCL-1 inhibitor with K_i and IC50 of 0.454 nM and 26.2 nM, respectively, >100-fold selectivity over other Bcl-2 family members.
Nutlin-3

Nutlin-3 is a potent and selective Mdm2 (RING finger-dependent ubiquitin protein ligase for itself and p53) antagonist with IC50 of 90 nM in a cell-free assay; stabilizes p73 in p53-deficient cells.
NSC 207895

NSC 207895 (XI-006) suppresses MDMX with IC50 of 2.5 μM, leading to enhanced p53 stabilization/activation and DNA damage, and also regulates MDM2, an E3 ligase.
Nutlin-3a

Nutlin-3a ((-)-Nutlin-3), the active enantiomer of Nutlin-3, inhibits the p53/MDM2 interaction with IC50 of 90 nM in a cell-free assay. Nutlin-3a induces autophagy and apoptosis in a p53-dependent manner.

Features:Highly selective MDM2 inhibitor with a much lower effect on MDMX. Most effective on tumors with wild type p53.
Nutlin-3b

Nutlin-3b ((+)-Nutlin-3) is a p53/MDM2 antagonist or inhibitor with IC50 value of 13.6 μM, 150-fold less potent (+)-enantiomer of Nutlin-3 as in comparison with opposite (-)-enantiomer Nutlin-3a.
YH239-EE

YH239-EE, the ethyl ester of YH239, is a potent p53-MDM2 antagonist and an apoptosis inducer.
Z-VAD-FMK

Z-VAD-FMK is a cell-permeable, irreversible pan-caspase inhibitor, blocks all features of apoptosis in THP.1 and Jurkat T-cells.

Features:A key compound for apoptosis studies.
Navitoclax (ABT-263)

Navitoclax (ABT-263) is a potent inhibitor of Bcl-xL, Bcl-2 and Bcl-w with K_i of ≤ 0.5 nM, ≤1 nM and ≤1 nM in cell-free assays, but binds more weakly to Mcl-1 and A1. Phase 2.

Choose Your Country or Region

By Signaling Pathways

By product type

RG-7112