AC710 Mesylate is a potent PDGFR inhibitor (Kds: 0.6, 1.57, 1, 1.3, 1.0 nM for FLT3, CSF1R, KIT, PDGFRα and PDGFRβ).

FLT3:0.6 nM (kd), c-Kit:1 nM (kd), PDGFRβ:1 nM (kd), PDGFRα:1.3 nM (kd), CSF1R:1.57 nM (kd)

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 bodyweight 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). AC710 (10 and 30 mg/kg) demonstrates equivalent or slightly better efficacy in reducing the joint swelling and inflammation than dexomethasone administered at a safe dose.

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 are monitored.