DS-6930 is an potent and selective PPAR γ Agonists with EC50 of 41 nM. DS-6930 can effectively reduce plasma glucose (PG) level, and has less PPARγ-related adverse effects compared with Rosiglitazone. DS-6930 has research value in diabetes.

PPARγ:41 nM (EC50)

DS-6930 demonstrates high in vitro potency with intermediate PPARγ agonist activity (EC50 = 41 nM, Emax = 68%) and exhibits high selectivity for PPARα and PPARδ (13% activation and no activation at 10 μM, respectively) [1]. DS-6930 (10-100 μM) also shows reduced cell toxicity at 100 μM [1].

DS-6930 administered orally at dosages ranging from 0.1 to 3 mg/kg for three weeks results in a dose-dependent decrease in plasma glucose (PG) levels in rats, with no significant impact on liver enzyme activities and relative heart weight after a higher dosage range of 100 to 1000 mg/kg for four weeks, indicating safety at studied doses. Additionally, pharmacokinetic analysis reveals DS-6930 achieves a maximum concentration (Cmax) of 0.0792 μg/mL and an area under the curve (AUC) of 0.861 h μg/mL 1.8 hours post-administration at a dose of 0.3 mg/kg by day 22 in rats. In cynomolgus monkeys, oral administration shows a Cmax of up to 2.25 μg/mL, a half-life (T1/2) of 13.5 hours, and an AUC of 23.5 h μg/mL at a 3 mg/kg dose, alongside excellent bioavailability (F=89%), total body clearance (CL=2.06 mL/min/kg), and steady-state distribution volume (Vss=0.36 L/kg) following intravenous administration of 1 mg/kg. A specific study in male ZDF rats demonstrates a 47% reduction in PG levels with a 0.3 mg/kg daily oral dose over three weeks, further underscoring DS-6930's efficacy and pharmacokinetic properties in animal models.