Pharmacological evaluation of HM41322, a novel SGLT1/2 dual inhibitor, in vitro and in vivo
- Authors
- Lee, Kyu Hang; Lee, Sang Don; Kim, Namdu; Suh, Kwee Hyun; Kim, Young Hoon; Sim, Sang Soo
- Issue Date
- Jan-2019
- Publisher
- KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
- Keywords
- Dapagliflozin; Diabetes mellitus; HM41322; SGLT1/2 dual inhibitor
- Citation
- KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY, v.23, no.1, pp 55 - 62
- Pages
- 8
- Journal Title
- KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
- Volume
- 23
- Number
- 1
- Start Page
- 55
- End Page
- 62
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/18366
- DOI
- 10.4196/kjpp.2019.23.1.55
- ISSN
- 1226-4512
2093-3827
- Abstract
- HM41322 is a novel oral sodium-glucose cotransporter (SGLT) 1/2 dual inhibitor. In this study, the in vitro and in vivo pharmacokinetic and pharmacologic profiles of HM41322 were compared to those of dapagliflozin. HM41322 showed a 10-fold selectivity for SGLT2 over SGLT1. HM41322 showed an inhibitory effect on SGLT2 similar to dapagliflozin, but showed a more potent inhibitory effect on SGLT1 than dapagliflozin. The maximum plasma HM41322 level after single oral doses at 0.1, 1, and 3 mg/kg were 142, 439, and 1830 ng/ml, respectively, and the T-1/2 was 3.1 h. HM41322 was rapidly absorbed and reached the circulation within 15 min. HM41322 maximized urinary glucose excretion by inhibiting both SGLT1 and SGLT2 in the kidney. HM41322 3 mg/kg caused the maximum urinary glucose excretion in normoglycemic mice (19.32 +/- 1.16 mg/g) at 24 h. In normal and diabetic mice, HM41322 significantly reduced glucose excursion. Four-week administration of HM41322 in db/db mice reduced HbA1c in a dose dependent manner. Taken together, HM41322 showed a favorable preclinical profile of postprandial glucose control through dual inhibitory activities against SGLT1 and SGLT2.
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