RG7112

SKU: orb1223580

Description

A potent and selective inhibitor of p53-MDM2 interaction; binds MDM2 with high affinity (Kd=11 nM); stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts. orally bioactive.(In Vitro):RG7112 (0-5 μM) stabilizes wild-type p53 and induces p53 signaling in cancer cells. RG7112 effectively activates p53 functions in cancer cells.(In Vivo):RG7112 (25-200 mg/kg, single oral dose) activates p53 pathway and induces apoptosis in tumor cells in vivo.RG7112 (100 mg/kg, gavage once per day, 5 days/week for 3 weeks ) reduces tumor growth rate and increases survival in GBM models.

Key Properties

• CAS Number: 939981-39-2
• MW: 727.7831
• Purity: >98% (HPLC)
• Formula: C₃₈H₄₈Cl₂N₄O₄S
• 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
• Target: MDM2-p53
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  Animal model: Female Balb/c nude mice. Dosage: 25-200 mg/kg. Administration: Orally, single dose. Result: At the highest dose level of RG7112 (200 mg/kg) only 1.2% (± 0.89 SD) of cells incorporated BrdU at 24 h post-dosing, vs. 14% (± 1.83 SD) of vehicle treated tumors. Animal model: GBM cells were implanted into the brain of Athymic Nude mice (7 weeks old females, 10 animals/group). Dosage: 100 mg/kg. Administration: Oral gavage, once per day, 5 days/week for 3 weeks. Result: Reduced tumor growth rate and increases survival in heterotopic and orthotopic animal models bearing MDM2-amplified GBM.
• In Vitro:
  Cell Proliferation Assay Cell line: SJSA1 osteosarcoma cells. Concentration: 0-5 μM. Incubation time: 0-60 hours. Result: Dose-dependently inhibited the growth and killed SJSA1 osteosarcoma cells expressing high levels of MDM2 protein due to MDM2 gene amplification. Cell Cycle Analysis Cell line: HCT116 and SJSA1 cells. Concentration: 0-5 μM. Incubation time: 48 hours. Result: Induced a dose-dependent cell cycle block in G1 and G2/M phase and depletion of the S phase compartment.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

RG-7112 | RG 7112

Quick Database Links

Gene Symbol

MDM2-p53