RG7112

Biological Activity

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.

Product Citations

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  Drug Des Devel Ther. 2019 Jan 14;13:317-326.

  YB-1 modulates the drug resistance of glioma cells by activation of MDM2/p53 pathway.
  RG7112 purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Oncotarget (2017). Figure 5. RG7112
	Method	gavage
	Cell Lines	MPM xenograft mouse
	Concentrations	100 mg/Kg
	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

Protocol

Cell Experiment
Cell lines
Preparation method
Concentrations
Incubation time

Animal Experiment
Animal models	SJSA-1, SJSA-1luc2, and MHM xenografted Balb/c nude mice
Formulation	1% Klucel LF/0.1% Tween 80
Dosages	25–200 mg/kg
Administration	oral

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

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 K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information

References

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.