Discovery of Canagliflozin, a Novel <i>C</i>-Glucoside with Thiophene Ring, as Sodium-Dependent Glucose Cotransporter 2 Inhibitor for the Treatment of Type 2 Diabetes Mellitus

Nomura, Sumihiro; Sakamaki, Shigeki; Hongu, Mitsuya; Kawanishi, Eiji; Koga, Yasuo; Sakamoto, Takabumi; Yamamoto, Yasuo; Ueta, Kiichiro; Kimata, Hirotaka; Nakayama, Keiko; Tsuda-Tsukimoto, Minoru

doi:10.1021/jm100332n

Cited by 338 publications

(231 citation statements)

References 25 publications

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“…Consequently, it can be said that there will be less hypoglycemic episodes with Canagliflozin. Furthermore, Canagliflozin remarkably increases the urinary glucose excretion [41]. At this moment in time Canagliflozin is under Phase-III clinical trial.…”

Section: Canagliflozinmentioning

confidence: 97%

An Emerging Protagonist: Sodium Glucose Co-transporters (SGLTs) as a Burgeoning Target for the Treatment of Diabetes Mellitus

et al. 2014

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Section: Canagliflozinmentioning

confidence: 97%

An Emerging Protagonist: Sodium Glucose Co-transporters (SGLTs) as a Burgeoning Target for the Treatment of Diabetes Mellitus

et al. 2014

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“…A novel thiophene derivative 4b-3 (canagliflozin) was a highly potent and selective SGLT-2 inhibitor and showed pronounced antihyperglycemic effects in high-fat diet fed KK (HF-KK) mice. 21 Canagliflozin improves glycemic control in an insulinindependent fashion through inhibition of glucose reuptake in the kidney. It offers a relatively modest reduction in HbA1c, FPG, and postprandial plasma glucose (PPG) (glycemic control).…”

Section: Canagliflozinmentioning

confidence: 99%

SGLT-2 inhibitors: the glucosuric antidiabetics

Thaddanee¹,

Khilnani²,

Khilnani³

2013

Int J Basic Clin Pharmacol

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Despite availability of a number of oral antidiabetics, a sizeable population of diabetics remains uncontrolled. Thus there is growing need of new group of drugs for diabetic control. Understanding renal conservation of glucose by efficient reabsorption through sodium glucose cotransporter-2 (SGLT-2) has paved way for development of an entirely new group of drugs, the SGLT-2 inhibitors. These glucosuric antidiabetic agents have shown promise in early clinical studies. Canagliflozin is recently approved for use in diabetes alone or along with other antidiabetics. Other highly selective inhibitors undergoing various stages of clinical developments are dapagliflozin, sergliflozin, remogliflozin, ipragliflozin, empagliflozin, luseogliflozin, tofogliflozin and desoxyrhaponticin. KGA-2727 (pyrazole-O-glucoside) is the first selective SGLT-1 inhibitor undergoing intense preclinical testing. There are safety issues associated with this group like urogenital infections (fungal), weight loss, initial osmotic diuresis and increased incidence of cardiovascular events. The long term safety remains to be established. Despite these limitations, SGLT-2 inhibition offers a unique target for achieving adequate control of diabetes in adults. [Int J Basic Clin Pharmacol 2013; 2(4.000): 347-352

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“…Canagliflozin, an orally active inhibitor of sodium glucose cotransporter 2 (SGLT2), is currently in development for the treatment of patients with type 2 diabetes mellitus [1][2]. Inhibition of SGLT2 causes inhibition of glucose reabsorption in renal proximal tubular cells, thereby reducing the renal threshold for glucose (RTG) [3][4].…”

Section: Introductionmentioning

confidence: 99%

A Validated Lc-MS/MS Method for Pharmacokinetic Study of Canagliflozin in Healthy Rabbits

Bhatt

Rajkamal

2018

Int J Pharm Pharm Sci

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Objective: A liquid chromatography-tandem mass spectrophotometric (LC-MS/MS) method was developed for quantification of canagliflozin in rabbit plasma employing Liquid-Liquid extraction technique. Methods:Chromatographic separation was achieved on Inertsil ODS 5 µm C18, 50×4.60 mm with 30:70 v/v of 0.01M ammonium acetate: methanol as an isocratic mobile phase with a flow rate of 0.8 ml/min. The developed LC-MS method was applied to assess Cmax, t1/2, AUC0-t, and AUC0-inf of canagliflozin tablet after oral administration in healthy rabbits. Results:The developed method was linear over working range of 5ng/ml to 600ng/ml with a coefficient of correction (r 2 ) = 0.999. The % recovery of the method was found to be 102.05%. The mean intraday and inter-day precision of the method was found to be 0.77 to 3.72%. The Canagliflozin showed Tmax of 1.58±0.2 and mean Cmax, AUC0→t and AUC0→α for Test formulation is 272±13.24, 2571.20±251and 2777.43±276 respectively. Conclusion:The developed method can be applied for routine analysis for quality control and the established LLOQ is sufficiently low to conduct a pharmacokinetic study with any marketing formulation of Canagliflozin in healthy rabbits.

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Discovery of Canagliflozin, a Novel C-Glucoside with Thiophene Ring, as Sodium-Dependent Glucose Cotransporter 2 Inhibitor for the Treatment of Type 2 Diabetes Mellitus

Cited by 338 publications

References 25 publications

An Emerging Protagonist: Sodium Glucose Co-transporters (SGLTs) as a Burgeoning Target for the Treatment of Diabetes Mellitus

An Emerging Protagonist: Sodium Glucose Co-transporters (SGLTs) as a Burgeoning Target for the Treatment of Diabetes Mellitus

SGLT-2 inhibitors: the glucosuric antidiabetics

A Validated Lc-MS/MS Method for Pharmacokinetic Study of Canagliflozin in Healthy Rabbits

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