title: In vitro characterization of luseogliflozin, a potent and competitive sodium glucose co-transporter 2 inhibitor: Inhibition kinetics and binding studies.
abstract: In this study, we evaluated an inhibition model of luseogliflozin on sodium glucose co-transporter 2 (SGLT2). We also analyzed the binding kinetics of the drug to SGLT2 protein using [(3)H]-luseogliflozin. Luseogliflozin competitively inhibited human SGLT2 (hSGLT2)-mediated glucose uptake with a Ki value of 1.10 nM. In the absence of glucose, [(3)H]-luseogliflozin exhibited a high affinity for hSGLT2 with a Kd value of 1.3 nM. The dissociation half-time was 7 h, suggesting that luseogliflozin dissociates rather slowly from hSGLT2. These profiles of luseogliflozin might contribute to the long duration of action of this drug.
authors.affiliation: Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama-shi, Saitama 331-9530, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Uchida
authors.affiliation: Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama-shi, Saitama 331-9530, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Mitani
authors.affiliation: Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama-shi, Saitama 331-9530, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Gunji
authors.affiliation: Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama-shi, Saitama 331-9530, Japan. Electronic address: te-takahashi@so.taisho.co.jp.
authors.forename: Teisuke
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama-shi, Saitama 331-9530, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D001665:Binding Sites; D001667:Binding, Competitive; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D007700:Kinetics; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013012:Sorbitol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D013997:Time Factors
chemical_list: D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013012:Sorbitol; C549343:1,5-anhydro-1-(5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl)-1-thioglucitol; D005947:Glucose
keywords: Binding kinetics; Inhibition model; Sodium glucose co-transporter 2 inhibitor