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Arisaph Pharmaceuticals Announces Results of its Potent Smart DPP-4,Inhibitor, ARI-2243, at the ADA

- ARI-2243 is an highly potent DPP-4 inhibitor, possessing Ki of 27 pM

BOSTON, June 25, 2007 /PRNewswire/ -- Arisaph Pharmaceuticals, Inc., a privately held drug discovery biopharmaceutical company, announced today the results of its potent, smart DPP-4 inhibitor, ARI-2243, presented at the 67th session of the American Diabetes Association meeting in Chicago, Illinois. The results showed that ARI-2243 is an extremely long acting, potent inhibitor of DPP-4 and produced superior reductions in plasma glucose compared with sitagliptin in oral glucose tolerance test (OGTT) in mice. Additionally, ARI-2243 produced significant reduction in hemoglobin A1c levels (HbA1c) following 9 weeks of daily oral dosing in an highly refractory diabetic animal model compared with no significant change with vildagliptin. The long-acting and potent attributes of ARI-2243 are expected to confer a differentiated efficacy profile in diabetic patients. Arisaph is currently completing IND enabling studies and expects to initiate first-in-man testing in 2008.

Arisaph designed ARI-2243 as a once a day, orally active, smart DPP-4 inhibitor that is highly potent and functionally selective. In vitro kinetic studies show that ARI-2243 has an affinity (Ki) of 27 picomolar, binding tightly to DPP-4 and dissociating very slowly from the enzyme. Such binding kinetics confer potency and long activity. Specifically, during OGTT in normal mice, ARI-2243 produced far greater lowering of plasma glucose compared with sitagliptin. Specifically, the ED50 with ARI-2243 was 0.006 mg/kg compared with sitagliptin, which had an ED50 of 1.5 mg/kg. Moreover, at 18 hours post dose, ARI-2243 lowered plasma AUC 25%, demonstrating long duration of action of the smart inhibitor.

In ZDF rats, an animal model that develops overt diabetes, ARI-2243 produced a significant reduction in HbA1c of 2.5% and 2.2% versus placebo and vildagliptin, respectively follo
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