1. Apoptosis
  2. MDM-2/p53

RG7112 (Synonyms: RO5045337)

Cat. No.: HY-10959 Purity: 99.94% ee.: 99.91%
Data Sheet SDS Handling Instructions

RG7112 is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2, with the Kd value of 11 nM.

For research use only. We do not sell to patients.
RG7112 Chemical Structure

RG7112 Chemical Structure

CAS No. : 939981-39-2

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $192 In-stock
5 mg $120 In-stock
10 mg $210 In-stock
25 mg $420 In-stock
50 mg $640 In-stock
100 mg $940 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Customer Review

    RG7112 purchased from MCE. Usage Cited in: Clin Cancer Res. 2016 Mar 1;22(5):1185-96.

    p53, p21 and MDM2 protein levels in MDM2-amplified GBM line treated with RG7112.

    RG7112 purchased from MCE. Usage Cited in: Oncotarget. 2016 Nov 15;7(46):75328-75338.

    Cell viability and activation of TP53 target proteins in clear cell carcinomas treated with RG7112. A and B. Time- (A) and dose-dependent (B) accumulation of MDM2, TP53, and TP21, as measured by western blotting. RG7112 is added at 2.5 μM in (A). C. Induction of TP53 phosphorylation and TP53 target proteins (TP21 and PUMA), as determined by western blotting. Cleaved PARP and survivin are also assessed to detect proapoptotic signaling.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    RG7112 is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2, with the Kd value of 11 nM.

    IC50 & Target

    Kd: 11 nM (MDM2)

    In Vitro

    RG7112 (2.5μM) is more active against proliferation of liposarcoma cells, and especially those with wild-type p53. Treatment of cells with either Nutlin-3A or RG7112 induces cell-cycle arrest and apoptosis in the p53-WT cell line 93T449. RG7112 treatment reduces cell viability much more than Nutlin-3A in HT-1080, SW684, 93T449, and SW872 cells[1]. RG7112 shows potent antitumor activity against a panel of solid tumor cell lines. Treatment of cancer cells expressing wild-type p53 with RG7112 activates the p53 pathway, leading to cell-cycle arrest and apoptosis[2].

    In Vivo

    RG7112 is highly synergistic with androgen deprivation in LNCaP xenograft tumors. RG7112 (25-200 mg/kg, p.o.) to human xenograft-bearing mice at nontoxic concentrations causes dose-dependent changes in proliferation/apoptosis biomarkers as well as tumor inhibition and regression[2].  

    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 1.3740 mL 6.8702 mL 13.7404 mL
    5 mM 0.2748 mL 1.3740 mL 2.7481 mL
    10 mM 0.1374 mL 0.6870 mL 1.3740 mL
    Please refer to the solubility information to select the appropriate solvent.
    Cell Assay
    [1]

    Sarcoma cells are seeded in 96-well E-plates with integral sensor electrode arrays. After 24 hrs, the cells are treated with different RG7112 concentrations and cell proliferation is monitored noninvasively, in real-time and label-free using the xCELLigence Real-Time Cell Analyzer for up to 72 hours. The 96-well E-plates used with the xCELLigence system have gold electrodes on their bottom surface, serving as sensors of alternating current modified by the number of adherent cells and cell status (including cell viability, morphology, and adhesion). A dimensionless parameter termed cell index (CI) is derived as a relative change in measured electrical impedance to represent cell status. CI normalized to the time of medium switch/treatment is presented in xCELLigence recordings. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2]

    RG7112 is suspended in vehicle (1% Klucel LF/0.1% Tween 80) at a concentration range of 25-200 mg/kg.

    For studies with hormone-dependent LNCaP xenografts, castrated male Balb/c nude are implanted with 12.5 mg sustained-release testosterone pellets 5 days before subcutaneous inoculation with 1×107 cells suspended in 0.2 mL of Matrigel:PBS. Mice are randomized into treatment groups (n=10 per group) when mean tumor volume reaches approximately 150 to 400 mm3. Mice receive either vehicle (1% Klucel LF/0.1% Tween 80) or RG7112, administered as an oral suspension at the dose indicated (25-200 mg/kg). For assessment of androgen ablation treatment in combination with RG7112 in LNCaP xenograft-bearing mice, testosterone pellets are removed under ketamine/xylazine anesthesia. Tumor volume is monitored by caliper measurement and body weights are recorded 2 to 3 times weekly. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    727.78

    Formula

    C₃₈H₄₈Cl₂N₄O₄S

    CAS No.

    939981-39-2

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    10 mM in DMSO

    RG7112 is formulated in 2% hydroxypropylcellulose, 0.1% Tween 80, 0.09% methylparaben and 0.01% propylparaben in water[3].
    RG7112 is suspended in 0.5 w/v% methyl cellulose 400[4].

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    References

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    Inquiry Information

    Product Name:
    RG7112
    Cat. No.:
    HY-10959
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