At 0.3 mg/kg of AC710, tumor growth is temporally inhibited, and growth resumes quickly thereafter. At 3 and 30 mg/kg of AC710, tumors regress completely, and the tumor volume stays suppressed for an extended period after dosing is halted. No body weight loss is observed in animals treated with AC710 at all doses, indicating that it is well tolerated in mice at efficacious doses. AC710 exhibits a significant impact on disease in a dose-dependent fashion in a mouse collagen-induced arthritis (CIA) model, at a dose as low as 3 mg/ kg for 15 days (day 0-14). At 10 and 30 mg/kg, AC710 demonstrates equivalent or slightly better efficacy in reducing the joint swelling and inflammation than dexomethasone administered at a safe dose. AC710 is well tolerated at the tested doses[1].
In Vitro
Kinase Assay
Cell Assay
Animal Administration
Mice: The antitumor efficacy of AC710 is assessed in a subcutaneous flank-tumor xenograft model in athymic nude mice using the MV4-11cell line. AC710 is dosed at 0.3, 3, and 30 mg/kg for 2 weeks. Tumor growth and body weight is monitored[1].
References
[1]. Liu G, et al. Discovery of AC710, a Globally Selective Inhibitor of Platelet-Derived Growth Factor Receptor-Family Kinases. ACS Med Chem Lett. 2012 Sep 24;3(12):997-1002.
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