Discovery of Ipragliflozin (ASP1941): A novel C-glucoside with benzothiophene structure as a potent and selective sodium glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes mellitus

Imamura, Masakazu; Nakanishi, Keita; Suzuki, Takayuki; Ikegai, Kazuhiro; Shiraki, Ryota; Ogiyama, Takashi; Murakami, Takeshi; Kurosaki, Eiji; Noda, Atsushi; Kobayashi, Yoshinori; Yokota, Masayuki; Koide, Tomokazu; Kosakai, Kazuhiro; Ohkura, Yasufumi; Takeuchi, Makoto; Tomiyama, Hiroshi; Ohta, Mitsuaki

doi:10.1016/j.bmc.2012.03.051

Cited by 118 publications

(75 citation statements)

References 25 publications

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“…Here, we investigated the effect of ipragliflozin, an orally active and selective SGLT2 inhibitor [20][21][22][23][24], on the simultaneous progression of diabetic retinopathy, nephropathy, and neuropathy in individual SDT fatty rats. …”

Section: Introductionmentioning

confidence: 99%

Effect of ipragliflozin, an SGLT2 inhibitor, on progression of diabetic microvascular complications in spontaneously diabetic Torii fatty rats

Takakura

Toyoshi²,

Hayashizaki

et al. 2016

Life Sciences

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Section: Introductionmentioning

confidence: 99%

Effect of ipragliflozin, an SGLT2 inhibitor, on progression of diabetic microvascular complications in spontaneously diabetic Torii fatty rats

Takakura

Toyoshi²,

Hayashizaki

et al. 2016

Life Sciences

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“…Empagliflozin exhibited the highest selectivity for SGLT2 vs. SGLT1 (Fig. ). Ipragliflozin (ASP‐1941) is a novel benzothiophene derivative that was discovered during optimization of a series of C ‐glycosides for selective inhibitory activity against SGLT2 vs. SGLT1 . It potently (n m range) inhibits mouse, rat and human SGLT2 and produces dose‐dependent and sustained antihyperglycaemic effects in mouse models of type 2 DM, but does not affect normoglycemia, intestinal glucose absorption or electrolyte balance .…”

Section: Resultsmentioning

confidence: 99%

The kidney as a new target for antidiabetic drugs: SGLT2 inhibitors

et al. 2013

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SUMMARYWhat is known and objective: A novel class of antidiabetic drugs -SGLT2 (Na + /glucose cotransporter type 2) inhibitors -target renal reabsorption of glucose and promote normal glucose levels, independent of insulin production or its action at receptors. We review this new mechanistic approach and the reported efficacy and safety of clinical testing of lead compounds. Methods: Information was obtained from various bibliographic sources, including PubMed and others, on the basic science and the clinical trials of SGLT2 inhibitors. The information was then summarized and evaluated from the perspective of contribution to a fuller understanding of the potential and current status of the lead clinical candidates. Results and discussion: Diabetes mellitus is a spectrum of disorders that involves inadequate insulin function resulting in adverse health sequelae due to acute and chronic hyperglycaemia. Current antidiabetic pharmacotherapy primarily addresses either insulin production at the pancreatic b-cells or insulin action at insulin receptors. These drugs have less than full clinical effectiveness and sometimes therapy-limiting adverse effects. The third major component of glucose balance, namely elimination, has not been a significant therapeutic target to date. SGLT2 inhibitors are a novel approach. What is new and conclusion: A sufficient number of clinical trials have been conducted on sufficiently chemically diverse SGLT2 inhibitors to reasonably conclude that they have efficacy (HbA1c reductions of 0Á4-1%), and thus far, the majority of adverse effects have been mild and transitory or treatable, with the caveat of possible association with increased risk of breast cancer in women and bladder cancer in men. WHAT IS KNOWN AND OBJECTIVEDiabetes mellitus (DM) is a metabolic disorder of inadequate glycaemic control, defined by the American Diabetes Association as a haemoglobin A1C (HgA1c) level ≥6Á5%.

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“…15), including dapagliflozin ( 56 ) 26 , empagliflozin ( 57 ) 27 , and ipragliflozin ( 58 ) 28 in 2014, and tofogliflozin ( 59 ) 29 is in the phase III clinical trials.…”

Section: Examples Of Successful Modificationsmentioning

confidence: 99%

The modification of natural products for medical use

Guo

2017

Acta Pharmaceutica Sinica B

260

156

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Drug innovation is characterized by painstaking molecular-level syntheses and modifications as the basic components of research and development. Similarly, natural products are chemically tailored and modified based upon their structural and biological properties. To some extent, the modification of natural products is quite different from de novo structure-based drug discovery. This review describes the general strategies and principles for the modification of natural products to drugs, as illustrated by several successful medicines that originated from natural products.

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Discovery of Ipragliflozin (ASP1941): A novel C-glucoside with benzothiophene structure as a potent and selective sodium glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes mellitus

Cited by 118 publications

References 25 publications

Effect of ipragliflozin, an SGLT2 inhibitor, on progression of diabetic microvascular complications in spontaneously diabetic Torii fatty rats

Effect of ipragliflozin, an SGLT2 inhibitor, on progression of diabetic microvascular complications in spontaneously diabetic Torii fatty rats

The kidney as a new target for antidiabetic drugs: SGLT2 inhibitors

The modification of natural products for medical use

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