RG7112 is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2. In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts.
|Source||Oncotarget (2017). Figure 5. RG7112|
|Cell Lines||MPM xenograft mouse|
|Incubation Time||days 1–21|
|Results||The in vivo relevance of the combined actions of MDM2 inhibition and TRAIL agonists was tested using a xenograft mouse model that recapitulates sarcomatoid MPM with WT p53. Interestingly, our results demonstrated that RG7112 plus rhTRAIL significantly reduced tumor growth compared to the mock-treated group|
|Animal models||SJSA-1, SJSA-1luc2, and MHM xenografted Balb/c nude mice|
|Formulation||1% Klucel LF/0.1% Tween 80|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development.
Vu B, et al. ACS Med Chem Lett. 2013 Apr 2;4(5):466-9. PMID: 24900694.
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