title: Pharmacological Characterization of YM543, a Newly Synthesized, Orally Active SGLT2 Selective Inhibitor.
abstract: OBJECTIVE
  Sodium-glucose cotransporter (SGLT) 2 is a specifically expressed transporter in the kidney that plays an important role in renal glucose reabsorption, and its inhibition may present a novel therapeutic strategy for treating diabetes. Here, we pharmacologically characterized YM543, a newly synthesized SGLT2 selective inhibitor to test this theory.
  
  
  RESULTS
  In vitro studies revealed that YM543 potently and selectively inhibited mouse and human SGLT2 activities at nanomolar ranges. In vivo single oral administration of YM543 dose-dependently and significantly reduced blood glucose levels and improved glucose tolerance with a concomitant increase in urinary glucose excretion in KK/Aytype 2 diabetic mice, effects that were sustained even after 12 h. Repeated once-daily oral administration of YM543 for 5 weeks significantly reduced hyperglycemia in type 2 diabetic mice. In addition, combination treatment of YM543 with rosiglitazone or metformin additively improved diabetic symptoms. In contrast, YM543 did not affect normoglycemia at pharmacological doses in normal mice.
  
  
  CONCLUSIONS
  Results from the present study suggest that YM543 is an orally active SGLT2 selective inhibitor which reduces hyperglycemia with a concomitant increase in urinary glucose excretion, indicating its promise as an effective treatment against type 2 diabetes.
authors: a Drug Discovery Research, Astellas Pharma Inc. , Tsukuba, Ibaraki, Japan.
authors: Masanori
authors: M
authors: Yokono
authors: a Drug Discovery Research, Astellas Pharma Inc. , Tsukuba, Ibaraki, Japan.
authors: Atsuo
authors: A
authors: Tahara
authors: a Drug Discovery Research, Astellas Pharma Inc. , Tsukuba, Ibaraki, Japan.
authors: Eiji
authors: E
authors: Kurosaki
authors: a Drug Discovery Research, Astellas Pharma Inc. , Tsukuba, Ibaraki, Japan.
authors: Daisuke
authors: D
authors: Yamajuku
authors: a Drug Discovery Research, Astellas Pharma Inc. , Tsukuba, Ibaraki, Japan.
authors: Rumi
authors: R
authors: Kihara
authors: a Drug Discovery Research, Astellas Pharma Inc. , Tsukuba, Ibaraki, Japan.
authors: Masakazu
authors: M
authors: Imamura
authors: b Research and Development Department, Kotobuki Pharmaceutical Co., Ltd. , Sakaki-machi, Hanishina-gun, Nagano, Japan.
authors: Hiroshi
authors: H
authors: Tomiyama
authors: c Research Laboratories, Kotobuki Pharmaceutical Co., Ltd. , Sakaki-machi, Hanishina-gun, Nagano, Japan.
authors: Yoshinori
authors: Y
authors: Kobayashi
authors: c Research Laboratories, Kotobuki Pharmaceutical Co., Ltd. , Sakaki-machi, Hanishina-gun, Nagano, Japan.
authors: Atsushi
authors: A
authors: Noda
authors: a Drug Discovery Research, Astellas Pharma Inc. , Tsukuba, Ibaraki, Japan.
authors: Masayuki
authors: M
authors: Shibasaki
keywords: Diabetes; Hyperglycemia; Sodium-glucose cotransporter 2; Urinary glucose excretion