Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Kakinuma H, Oi T, Hashimoto-Tsuchiya Y, Arai M, Kawakita Y, Fukasawa Y, Iida I, Hagima N, Takeuchi H, Chino Y, Asami J, Okumura-Kitajima L, Io F, Yamamoto D, Miyata N, Takahashi T, Uchida S, Yamamoto K. (1S)-1,5-anhydro-1-[5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl]-1-thio-D-glucitol (TS-071) is a potent, selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for type 2 diabetes treatment. J Med Chem 2010;53:3247-61. [PMID: 20302302 DOI: 10.1021/jm901893x] [Citation(s) in RCA: 119] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]

For:	Kakinuma H, Oi T, Hashimoto-Tsuchiya Y, Arai M, Kawakita Y, Fukasawa Y, Iida I, Hagima N, Takeuchi H, Chino Y, Asami J, Okumura-Kitajima L, Io F, Yamamoto D, Miyata N, Takahashi T, Uchida S, Yamamoto K. (1S)-1,5-anhydro-1-[5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl]-1-thio-D-glucitol (TS-071) is a potent, selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for type 2 diabetes treatment. J Med Chem 2010;53:3247-61. [PMID: 20302302 DOI: 10.1021/jm901893x] [Citation(s) in RCA: 119] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]

Number

Cited by Other Article(s)

Xu Z, Geng Y, Guan L, Niu MM, Xu C, Yang L, Liang S. Discovery of a highly potent, selective, and stable d-amino acid-containing peptide inhibitor of CDK9/cyclin T1 interaction for the treatment of prostate cancer. Eur J Med Chem 2025;285:117248. [PMID: 39808974 DOI: 10.1016/j.ejmech.2025.117248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 01/05/2025] [Accepted: 01/05/2025] [Indexed: 01/16/2025]

Takamiya Y, Imanaga C, Abe I, Kobayashi K, Ike A, Kawamura A, Urata H. Long-term renoprotective effect of luseogliflozin in type 2 diabetes patients: CHikushi Anti-diabetes mellitus Trial-Lusefi (CHAT-Lu). Drug Discov Ther 2025;18:336-342. [PMID: 39756883 DOI: 10.5582/ddt.2024.01086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2025]

Galigutta RR, Hasik PN, Thomas C, Undela K. Efficacy and safety of luseogliflozin in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Endocrine 2024;86:620-630. [PMID: 38884927 DOI: 10.1007/s12020-024-03925-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Accepted: 06/06/2024] [Indexed: 06/18/2024]

Abstract

PURPOSE

Owing to the absence of the most recent evidence on the efficacy and safety of luseogliflozin, our study aimed to conduct a systematic review and meta-analysis of luseogliflozin in patients with type 2 diabetes mellitus.

METHODS

A comprehensive search of electronic databases like PubMed, Cochrane CENTRAL, and Google Scholar was performed from the inception to the 31st of August 2023 to identify the randomized controlled trials (RCTs) that examined the glucose and body weight lowering efficacy and safety outcomes of luseogliflozin in comparison with control or other active treatments. The fixed or random-effect model was used based on the heterogeneity identified using the I2 statistic and Cochran's Q test.

RESULTS

Out of 50 non-duplicate articles identified through database searching, 8 RCTs (11 studies) with 1922 patients were included in this study. The efficacy outcomes like HbA1c (MD: -0.59%; 95% CI: -0.90, -0.29; P < 0.001), FPG (MD: -16.01 mg/dL; 95% CI: -19.46, -12.57; P < 0.001), PPG (MD: -36.63 mg/dL; 95% CI: -43.71, -29.55; P < 0.001) and body weight (MD: -1.66 kg; 95% CI: -2.23, -1.12; P < 0.001) were significantly reduced with luseogliflozin compared to the control group. Regarding the safety outcomes, there was no statistically significant difference between the two groups for hypoglycemia (OR: 1.14; 95% CI: 0.70, 1.84; P = 0.60). However, pollakiuria (OR: 4.08; 95% CI: 1.71, 9.69; P < 0.001) and any ADRs (OR: 2.04; 95% CI: 1.33, 3.14; P < 0.001) were significantly higher in the luseogliflozin group compared to the control.

CONCLUSION

The current study identified a significant improvement in efficacy outcomes of HbA1c, FPG, PPG, and body weight in the luseogliflozin group. Non-significant safety results may be due to a smaller population size and fewer studies. Hence, long-term multicentric RCTs are needed to identify the safety and efficacy in a diversified population.

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Sato H, Ishikawa A, Yoshioka H, Jin R, Sano Y, Hisaka A. Model-based meta-analysis of HbA1c reduction across SGLT2 inhibitors using dose adjusted by urinary glucose excretion. Sci Rep 2024;14:24695. [PMID: 39433865 PMCID: PMC11493964 DOI: 10.1038/s41598-024-76256-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Accepted: 10/11/2024] [Indexed: 10/23/2024] Open

Chiodi D, Ishihara Y. The role of the methoxy group in approved drugs. Eur J Med Chem 2024;273:116364. [PMID: 38781921 DOI: 10.1016/j.ejmech.2024.116364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 03/12/2024] [Accepted: 03/23/2024] [Indexed: 05/25/2024]

Albalawy WN, Youm EB, Shipman KE, Trull KJ, Baty CJ, Long KR, Rbaibi Y, Wang XP, Fagunloye OG, White KA, Jurczak MJ, Kashlan OB, Weisz OA. SGLT2-independent effects of canagliflozin on NHE3 and mitochondrial complex I activity inhibit proximal tubule fluid transport and albumin uptake. Am J Physiol Renal Physiol 2024;326:F1041-F1053. [PMID: 38660713 PMCID: PMC11381006 DOI: 10.1152/ajprenal.00005.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 04/03/2024] [Accepted: 04/18/2024] [Indexed: 04/26/2024] Open

Abstract

Beyond glycemic control, SGLT2 inhibitors (SGLT2is) have protective effects on cardiorenal function. Renoprotection has been suggested to involve inhibition of NHE3 leading to reduced ATP-dependent tubular workload and mitochondrial oxygen consumption. NHE3 activity is also important for regulation of endosomal pH, but the effects of SGLT2i on endocytosis are unknown. We used a highly differentiated cell culture model of proximal tubule (PT) cells to determine the direct effects of SGLT2i on Na+-dependent fluid transport and endocytic uptake in this nephron segment. Strikingly, canagliflozin but not empagliflozin reduced fluid transport across cell monolayers and dramatically inhibited endocytic uptake of albumin. These effects were independent of glucose and occurred at clinically relevant concentrations of drug. Canagliflozin acutely inhibited surface NHE3 activity, consistent with a direct effect, but did not affect endosomal pH or NHE3 phosphorylation. In addition, canagliflozin rapidly and selectively inhibited mitochondrial complex I activity. Inhibition of mitochondrial complex I by metformin recapitulated the effects of canagliflozin on endocytosis and fluid transport, whereas modulation of downstream effectors AMPK and mTOR did not. Mice given a single dose of canagliflozin excreted twice as much urine over 24 h compared with empagliflozin-treated mice despite similar water intake. We conclude that canagliflozin selectively suppresses Na+-dependent fluid transport and albumin uptake in PT cells via direct inhibition of NHE3 and of mitochondrial function upstream of the AMPK/mTOR axis. These additional targets of canagliflozin contribute significantly to reduced PT Na+-dependent fluid transport in vivo.NEW & NOTEWORTHY Reduced NHE3-mediated Na+ transport has been suggested to underlie the cardiorenal protection provided by SGLT2 inhibitors. We found that canagliflozin, but not empagliflozin, reduced NHE3-dependent fluid transport and endocytic uptake in cultured proximal tubule cells. These effects were independent of SGLT2 activity and resulted from inhibition of mitochondrial complex I and NHE3. Studies in mice are consistent with greater effects of canagliflozin versus empagliflozin on fluid transport. Our data suggest that these selective effects of canagliflozin contribute to reduced Na+-dependent transport in proximal tubule cells.

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Affiliation(s)

Wafaa N Albalawy Department of Human Genetics, Pitt Public Health, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
Elynna B Youm Department of Human Genetics, Pitt Public Health, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
Katherine E Shipman Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
Keelan J Trull Department of Chemistry and Biochemistry, University of Notre Dame, South Bend, Indiana, United States
Catherine J Baty Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
Kimberly R Long Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
Youssef Rbaibi Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
Xue-Ping Wang Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
Olayemi G Fagunloye Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
Katharine A White Department of Chemistry and Biochemistry, University of Notre Dame, South Bend, Indiana, United States
Michael J Jurczak Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
Ossama B Kashlan Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
Ora A Weisz Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States

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Xie T, Zhao LJ. Synthetic approaches and clinical application of small-molecule inhibitors of sodium-dependent glucose transporters 2 for the treatment of type 2 diabetes mellitus. Eur J Med Chem 2024;269:116343. [PMID: 38513341 DOI: 10.1016/j.ejmech.2024.116343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 03/08/2024] [Accepted: 03/15/2024] [Indexed: 03/23/2024]

Wakamatsu S, Jojima T, Hashiguchi M, Kishi H, Niitani T, Sakurai S, Iijima T, Kogai T, Tomaru T, Usui I, Aso Y. Inhibition of IL-33 signaling ameliorate hepatic fibrosis with decreasing MCP-1 in a mouse model of diabetes and non-alcoholic steatohepatitis; comparison for luseogliflozin, an SGLT2 inhibitor. J Diabetes Complications 2024;38:108650. [PMID: 38035640 DOI: 10.1016/j.jdiacomp.2023.108650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 10/16/2023] [Accepted: 11/19/2023] [Indexed: 12/02/2023]

Shim B, Stokum JA, Moyer M, Tsymbalyuk N, Tsymbalyuk O, Keledjian K, Ivanova S, Tosun C, Gerzanich V, Simard JM. Canagliflozin, an Inhibitor of the Na⁺-Coupled D-Glucose Cotransporter, SGLT2, Inhibits Astrocyte Swelling and Brain Swelling in Cerebral Ischemia. Cells 2023;12:2221. [PMID: 37759444 PMCID: PMC10527352 DOI: 10.3390/cells12182221] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 08/28/2023] [Accepted: 09/05/2023] [Indexed: 09/29/2023] Open

Affiliation(s)

Bosung Shim Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.S.); (J.A.S.); (M.M.); (N.T.); (O.T.); (K.K.); (S.I.); (C.T.); (V.G.)
Jesse A. Stokum Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.S.); (J.A.S.); (M.M.); (N.T.); (O.T.); (K.K.); (S.I.); (C.T.); (V.G.)
Mitchell Moyer Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.S.); (J.A.S.); (M.M.); (N.T.); (O.T.); (K.K.); (S.I.); (C.T.); (V.G.)
Natalya Tsymbalyuk Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.S.); (J.A.S.); (M.M.); (N.T.); (O.T.); (K.K.); (S.I.); (C.T.); (V.G.)
Orest Tsymbalyuk Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.S.); (J.A.S.); (M.M.); (N.T.); (O.T.); (K.K.); (S.I.); (C.T.); (V.G.)
Kaspar Keledjian Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.S.); (J.A.S.); (M.M.); (N.T.); (O.T.); (K.K.); (S.I.); (C.T.); (V.G.)
Svetlana Ivanova Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.S.); (J.A.S.); (M.M.); (N.T.); (O.T.); (K.K.); (S.I.); (C.T.); (V.G.)
Cigdem Tosun Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.S.); (J.A.S.); (M.M.); (N.T.); (O.T.); (K.K.); (S.I.); (C.T.); (V.G.)
Volodymyr Gerzanich Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.S.); (J.A.S.); (M.M.); (N.T.); (O.T.); (K.K.); (S.I.); (C.T.); (V.G.)
J. Marc Simard Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (B.S.); (J.A.S.); (M.M.); (N.T.); (O.T.); (K.K.); (S.I.); (C.T.); (V.G.) Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA

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Seki M, Tapkir SR, Nadiveedhi MR, Mulani SK, Mashima K. New Synthesis of Diarylmethanes, Key Building Blocks for SGLT2 Inhibitors. ACS OMEGA 2023;8:17288-17295. [PMID: 37214716 PMCID: PMC10193421 DOI: 10.1021/acsomega.3c01972] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 04/28/2023] [Indexed: 05/24/2023]

Imai Y, Wakasugi D, Suzuki R, Kato S, Sugisaki M, Mima M, Miyagawa H, Endo M, Fujimoto N, Fukunaga T, Kato S, Kuroda S, Takahashi T, Kakinuma H. Lead identification of novel tetrahydroimidazo[1,2-a]pyridine-5-carboxylic acid derivative as a potent heparanase-1 inhibitor. Bioorg Med Chem Lett 2023;79:129050. [PMID: 36368497 DOI: 10.1016/j.bmcl.2022.129050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 10/28/2022] [Accepted: 11/03/2022] [Indexed: 11/09/2022]

Affiliation(s)

Yudai Imai Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.
Daisuke Wakasugi Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan
Ryo Suzuki Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan
Sota Kato Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan
Mami Sugisaki Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan
Masashi Mima Discovery Technologies Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan
Hiroh Miyagawa Discovery Technologies Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan
Mayumi Endo Discovery Technologies Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan
Natsuko Fujimoto Discovery Technologies Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan
Takuya Fukunaga Discovery Technologies Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan
Sayaka Kato Discovery Technologies Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan
Shoichi Kuroda Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan
Teisuke Takahashi Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan
Hiroyuki Kakinuma Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan

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Wang Z, Wang G, Ren J. Using a Mathematical Modeling To Simulate Pharmacokinetics and Urinary Glucose Excretion of Luseogliflozin and Explore the Role of SGLT1/2 in Renal Glucose Reabsorption. ACS OMEGA 2022;7:48427-48437. [PMID: 36591124 PMCID: PMC9798748 DOI: 10.1021/acsomega.2c06483] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 12/06/2022] [Indexed: 06/17/2023]

Cao X, Du X, Jiao H, An Q, Chen R, Fang P, Wang J, Yu B. Carbohydrate-based drugs launched during 2000-2021. Acta Pharm Sin B 2022;12:3783-3821. [PMID: 36213536 PMCID: PMC9532563 DOI: 10.1016/j.apsb.2022.05.020] [Citation(s) in RCA: 103] [Impact Index Per Article: 34.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 04/18/2022] [Accepted: 05/12/2022] [Indexed: 01/09/2023] Open

Wan X, Li H, Wang S, Wang C. Acetic Acid Mediated Regioselective [3 + 3] Cycloaddition of Substituted Cyclopropane-1,1-dicarbonitriles with 1,4-Dithiane-2,5-diol. J Org Chem 2022;87:13375-13382. [PMID: 36166746 DOI: 10.1021/acs.joc.2c01610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]

Maccari R, Ottanà R. Sodium-Glucose Cotransporter Inhibitors as Antidiabetic Drugs: Current Development and Future Perspectives. J Med Chem 2022;65:10848-10881. [PMID: 35924548 PMCID: PMC9937539 DOI: 10.1021/acs.jmedchem.2c00867] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]

Takashima M, Nakamura K, Kiyohara T, Wakisaka Y, Hidaka M, Takaki H, Yamanaka K, Shibahara T, Wakisaka M, Ago T, Kitazono T. Low-dose sodium-glucose cotransporter 2 inhibitor ameliorates ischemic brain injury in mice through pericyte protection without glucose-lowering effects. Commun Biol 2022;5:653. [PMID: 35780235 PMCID: PMC9250510 DOI: 10.1038/s42003-022-03605-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Accepted: 06/20/2022] [Indexed: 12/11/2022] Open

Luseogliflozin preserves the pancreatic beta-cell mass and function in db/db mice by improving mitochondrial function. Sci Rep 2022;12:9740. [PMID: 35697838 PMCID: PMC9192642 DOI: 10.1038/s41598-022-13888-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 05/30/2022] [Indexed: 11/20/2022] Open

Role of Sodium-Glucose Co-Transporter 2 Inhibitors in the Regulation of Inflammatory Processes in Animal Models. Int J Mol Sci 2022;23:ijms23105634. [PMID: 35628443 PMCID: PMC9144929 DOI: 10.3390/ijms23105634] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 05/14/2022] [Accepted: 05/16/2022] [Indexed: 12/12/2022] Open

Sasikala CVA, Annapragada R, Basu D, Singarapu KK, Mohammad A, Bandichhor R. Efficient Route to Canagliflozin via Anhydroketopyranose. Org Lett 2022;24:3450-3454. [PMID: 35522756 DOI: 10.1021/acs.orglett.2c00980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]

Discovery of GCC5694A: A potent and selective sodium glucose co-transporter 2 inhibitor for the treatment of type 2 diabetes. Bioorg Med Chem Lett 2022;56:128466. [PMID: 34813882 DOI: 10.1016/j.bmcl.2021.128466] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 11/03/2021] [Accepted: 11/12/2021] [Indexed: 11/22/2022]

Sharma S, Mittal A, Kumar S, Mittal A. Structural Perspectives and Advancement of SGLT2 Inhibitors for the Treatment of Type 2 Diabetes. Curr Diabetes Rev 2022;18:e170921196601. [PMID: 34538233 DOI: 10.2174/1573399817666210917122745] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 08/12/2021] [Accepted: 08/14/2021] [Indexed: 11/22/2022]

Moinul M, Amin SA, Kumar P, Patil UK, Gajbhiye A, Jha T, Gayen S. Exploring sodium glucose cotransporter (SGLT2) inhibitors with machine learning approach: A novel hope in anti-diabetes drug discovery. J Mol Graph Model 2021;111:108106. [PMID: 34923429 DOI: 10.1016/j.jmgm.2021.108106] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 11/15/2021] [Accepted: 12/06/2021] [Indexed: 12/29/2022]

Faria J, Gerritsen KGF, Nguyen TQ, Mihaila SM, Masereeuw R. Diabetic proximal tubulopathy: Can we mimic the disease for in vitro screening of SGLT inhibitors? Eur J Pharmacol 2021;908:174378. [PMID: 34303664 DOI: 10.1016/j.ejphar.2021.174378] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 07/15/2021] [Accepted: 07/21/2021] [Indexed: 11/27/2022]

Gandhi A, Masand V, Zaki MEA, Al-Hussain SA, Ghorbal AB, Chapolikar A. QSAR analysis of sodium glucose co-transporter 2 (SGLT2) inhibitors for anti-hyperglycaemic lead development. SAR AND QSAR IN ENVIRONMENTAL RESEARCH 2021;32:731-744. [PMID: 34494464 DOI: 10.1080/1062936x.2021.1971295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 08/18/2021] [Indexed: 06/13/2023]

Estrada AK, Delgado-Maldonado T, Lara-Ramírez EE, Martínez-Vázquez AV, Ortiz-Lopez E, Paz-González AD, Bandyopadhyay D, Rivera G. Recent Advances in the Development of Type 2 Sodium-Glucose Cotransporter Inhibitors for the Treatment of Type 2 Diabetes Mellitus. Mini Rev Med Chem 2021;22:586-599. [PMID: 34353256 DOI: 10.2174/1389557521666210805112416] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 06/09/2021] [Accepted: 06/16/2021] [Indexed: 11/22/2022]

Sipos Á, Szennyes E, Hajnal NÉ, Kun S, Szabó KE, Uray K, Somsák L, Docsa T, Bokor É. Dual-Target Compounds against Type 2 Diabetes Mellitus: Proof of Concept for Sodium Dependent Glucose Transporter (SGLT) and Glycogen Phosphorylase (GP) Inhibitors. Pharmaceuticals (Basel) 2021;14:ph14040364. [PMID: 33920838 PMCID: PMC8071193 DOI: 10.3390/ph14040364] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/07/2021] [Accepted: 04/13/2021] [Indexed: 12/15/2022] Open

Abstract

A current trend in the quest for new therapies for complex, multifactorial diseases, such as diabetes mellitus (DM), is to find dual or even multi-target inhibitors. In DM, the sodium dependent glucose cotransporter 2 (SGLT2) in the kidneys and the glycogen phosphorylase (GP) in the liver are validated targets. Several (β-D-glucopyranosylaryl)methyl (het)arene type compounds, called gliflozins, are marketed drugs that target SGLT2. For GP, low nanomolar glucose analogue inhibitors exist. The purpose of this study was to identify dual acting compounds which inhibit both SGLTs and GP. To this end, we have extended the structure-activity relationships of SGLT2 and GP inhibitors to scarcely known (C-β-D-glucopyranosylhetaryl)methyl arene type compounds and studied several (C-β-D-glucopyranosylhetaryl)arene type GP inhibitors against SGLT. New compounds, such as 5-arylmethyl-3-(β-D-glucopyranosyl)-1,2,4-oxadiazoles, 5-arylmethyl-2-(β-D-glucopyranosyl)-1,3,4-oxadiazoles, 4-arylmethyl-2-(β-D-glucopyranosyl)pyrimidines and 4(5)-benzyl-2-(β-D-glucopyranosyl)imidazole were prepared by adapting our previous synthetic methods. None of the studied compounds exhibited cytotoxicity and all of them were assayed for their SGLT1 and 2 inhibitory potentials in a SGLT-overexpressing TSA201 cell system. GP inhibition was also determined by known methods. Several newly synthesized (C-β-D-glucopyranosylhetaryl)methyl arene derivatives had low micromolar SGLT2 inhibitory activity; however, none of these compounds inhibited GP. On the other hand, several (C-β-D-glucopyranosylhetaryl)arene type GP inhibitor compounds with low micromolar efficacy against SGLT2 were identified. The best dual inhibitor, 2-(β-D-glucopyranosyl)-4(5)-(2-naphthyl)-imidazole, had a K_i of 31 nM for GP and IC₅₀ of 3.5 μM for SGLT2. This first example of an SGLT-GP dual inhibitor can prospectively be developed into even more efficient dual-target compounds with potential applications in future antidiabetic therapy.

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Affiliation(s)

Ádám Sipos Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary; (Á.S.); (K.U.) Doctoral School of Molecular Medicine, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary
Eszter Szennyes Department of Organic Chemistry, University of Debrecen, POB 400, H-4002 Debrecen, Hungary; (E.S.); (N.É.H.); (S.K.); (K.E.S.)
Nikolett Éva Hajnal Department of Organic Chemistry, University of Debrecen, POB 400, H-4002 Debrecen, Hungary; (E.S.); (N.É.H.); (S.K.); (K.E.S.)
Sándor Kun Department of Organic Chemistry, University of Debrecen, POB 400, H-4002 Debrecen, Hungary; (E.S.); (N.É.H.); (S.K.); (K.E.S.)
Katalin E. Szabó Department of Organic Chemistry, University of Debrecen, POB 400, H-4002 Debrecen, Hungary; (E.S.); (N.É.H.); (S.K.); (K.E.S.)
Karen Uray Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary; (Á.S.); (K.U.)
László Somsák Department of Organic Chemistry, University of Debrecen, POB 400, H-4002 Debrecen, Hungary; (E.S.); (N.É.H.); (S.K.); (K.E.S.) Correspondence: (L.S.); (T.D.); (É.B.); Tel.: +36-525-129-00 (ext. 22348) (L.S.); +36-525-186-00 (ext. 61192) (T.D.); +36-525-129-00 (ext. 22474) (É.B.)
Tibor Docsa Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary; (Á.S.); (K.U.) Correspondence: (L.S.); (T.D.); (É.B.); Tel.: +36-525-129-00 (ext. 22348) (L.S.); +36-525-186-00 (ext. 61192) (T.D.); +36-525-129-00 (ext. 22474) (É.B.)
Éva Bokor Department of Organic Chemistry, University of Debrecen, POB 400, H-4002 Debrecen, Hungary; (E.S.); (N.É.H.); (S.K.); (K.E.S.) Correspondence: (L.S.); (T.D.); (É.B.); Tel.: +36-525-129-00 (ext. 22348) (L.S.); +36-525-186-00 (ext. 61192) (T.D.); +36-525-129-00 (ext. 22474) (É.B.)

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de Matos AM, Calado P, Washburn W, Rauter AP. Recent Advances on SGLT 2 Inhibitors: Synthetic Approaches, Therapeutic Benefits, and Adverse Events. SUCCESSFUL DRUG DISCOVERY 2021:111-157. [DOI: 10.1002/9783527826872.ch4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]

SGLT2 inhibitors, an accomplished development in field of medicinal chemistry: an extensive review. Future Med Chem 2020;12:1961-1990. [DOI: 10.4155/fmc-2020-0154] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open

Mukkamala R, Kumar R, Banerjee SK, Aidhen IS. Synthesis of Benzyl C -Analogues of Dapagliflozin as Potential SGLT2 Inhibitors. European J Org Chem 2020. [DOI: 10.1002/ejoc.202000025] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]

Shirakawa J, Tajima K, Okuyama T, Kyohara M, Togashi Y, De Jesus DF, Basile G, Kin T, Shapiro AMJ, Kulkarni RN, Terauchi Y. Luseogliflozin increases beta cell proliferation through humoral factors that activate an insulin receptor- and IGF-1 receptor-independent pathway. Diabetologia 2020;63:577-587. [PMID: 31897526 PMCID: PMC7574158 DOI: 10.1007/s00125-019-05071-w] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Accepted: 11/13/2019] [Indexed: 02/07/2023]

Abstract

AIMS/HYPOTHESIS

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, which prevent the renal reabsorption of glucose, decrease blood glucose levels in an insulin-independent manner. We previously reported creating a mouse model of systemic inhibition of target receptors for both insulin and IGF-1 by treating animals with OSI-906, a dual insulin/IGF-1 receptor inhibitor, for 7 days. The OSI-906-treated mice exhibited an increased beta cell mass, hepatic steatosis and adipose tissue atrophy, accompanied by hyperglycaemia and hyperinsulinaemia. In the present study, we investigated the effects of an SGLT2 inhibitor, luseogliflozin, on these changes in OSI-906-treated mice.

METHODS

We treated C57BL/6J male mice either with vehicle, luseogliflozin, OSI-906 or OSI-906 plus luseogliflozin for 7 days, and phenotyping was performed to determine beta cell mass and proliferation. Subsequently, we tested whether serum-derived factors have an effect on beta cell proliferation in genetically engineered beta cells, mouse islets or human islets.

RESULTS

SGLT2 inhibition with luseogliflozin significantly ameliorated hyperglycaemia, but not hyperinsulinaemia, in the OSI-906-treated mice. Liver steatosis and adipose tissue atrophy induced by OSI-906 were not altered by treatment with luseogliflozin. Beta cell mass and proliferation were further increased by SGLT2 inhibition with luseogliflozin in the OSI-906-treated mice. Luseogliflozin upregulated gene expression related to the forkhead box M1 (FoxM1)/polo-like kinase 1 (PLK1)/centromere protein A (CENP-A) pathway in the islets of OSI-906-treated mice. The increase in beta cell proliferation was recapitulated in a co-culture of Irs2 knockout and Insr/IR knockout (βIRKO) beta cells with serum from both luseogliflozin- and OSI-906-treated mice, but not after SGLT2 inhibition in beta cells. Circulating factors in both luseogliflozin- and OSI-906-treated mice promoted beta cell proliferation in both mouse islets and cadaveric human islets.

CONCLUSIONS/INTERPRETATION

These results suggest that luseogliflozin can increase beta cell proliferation through the activation of the FoxM1/PLK1/CENP-A pathway via humoral factors that act in an insulin/IGF-1 receptor-independent manner.

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Romero FA, Jones CT, Xu Y, Fenaux M, Halcomb RL. The Race to Bash NASH: Emerging Targets and Drug Development in a Complex Liver Disease. J Med Chem 2020;63:5031-5073. [PMID: 31930920 DOI: 10.1021/acs.jmedchem.9b01701] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]

Kshirsagar RP, Kulkarni AA, Chouthe RS, Pathan SK, Une HD, Reddy GB, Diwan PV, Ansari SA, Sangshetti JN. SGLT inhibitors as antidiabetic agents: a comprehensive review. RSC Adv 2020;10:1733-1756. [PMID: 35494673 PMCID: PMC9048284 DOI: 10.1039/c9ra08706k] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Accepted: 12/18/2019] [Indexed: 12/12/2022] Open

Haider K, Pathak A, Rohilla A, Haider MR, Ahmad K, Yar MS. Synthetic strategy and SAR studies of C-glucoside heteroaryls as SGLT2 inhibitor: A review. Eur J Med Chem 2019;184:111773. [DOI: 10.1016/j.ejmech.2019.111773] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 07/09/2019] [Accepted: 10/08/2019] [Indexed: 12/25/2022]

Wang Y, Lou Y, Wang J, Li D, Chen H, Zheng T, Xia C, Song X, Dong T, Li J, Li J, Liu H. Design, synthesis and biological evaluation of 6-deoxy O-spiroketal C-arylglucosides as novel renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes. Eur J Med Chem 2019;180:398-416. [DOI: 10.1016/j.ejmech.2019.07.032] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Revised: 07/09/2019] [Accepted: 07/09/2019] [Indexed: 12/25/2022]

Hu L, Zou P, Wei W, Yuan XM, Qiu XL, Gou SH. Facile and green synthesis of dapagliflozin. SYNTHETIC COMMUN 2019. [DOI: 10.1080/00397911.2019.1666283] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]

Pałasz A, Cież D, Trzewik B, Miszczak K, Tynor G, Bazan B. In the Search of Glycoside-Based Molecules as Antidiabetic Agents. Top Curr Chem (Cham) 2019;377:19. [PMID: 31165274 PMCID: PMC6548768 DOI: 10.1007/s41061-019-0243-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 05/14/2019] [Indexed: 02/06/2023]

Abstract

This review is an effort to summarize recent developments in synthesis of O-glycosides and N-, C-glycosyl molecules with promising antidiabetic potential. Articles published after 2000 are included. First, the O-glycosides used in the treatment of diabetes are presented, followed by the N-glycosides and finally the C-glycosides constituting the largest group of antidiabetic drugs are described. Within each group of glycosides, we presented how the structure of compounds representing potential drugs changes and when discussing chemical compounds of a similar structure, achievements are presented in the chronological order. C-Glycosyl compounds mimicking O-glycosides structure, exhibit the best features in terms of pharmacodynamics and pharmacokinetics. Therefore, the largest part of the article is concerned with the description of the synthesis and biological studies of various C-glycosides. Also N-glycosides such as N-(β-d-glucopyranosyl)-amides, N-(β-d-glucopyranosyl)-ureas, and 1,2,3-triazolyl derivatives belong to the most potent classes of antidiabetic agents. In order to indicate which of the compounds presented in the given sections have the best inhibitory properties, a list of the best inhibitors is presented at the end of each section. In summary, the best inhibitors were selected from each of the summarizing figures and the results of the ranking were placed. In this way, the reader can learn about the structure of the compounds having the best antidiabetic activity. The compounds, whose synthesis was described in the article but did not appear on the figures presenting the structures of the most active inhibitors, did not show proper activity as inhibitors. Thus, the article also presents studies that have not yielded the desired results and show directions of research that should not be followed. In order to show the directions of the latest research, articles from 2018 to 2019 are described in a separate Sect. 5. In Sect. 6, biological mechanisms of action of the glycosides and patents of marketed drugs are described.

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Dominguez Rieg JA, Rieg T. What does sodium-glucose co-transporter 1 inhibition add: Prospects for dual inhibition. Diabetes Obes Metab 2019;21 Suppl 2:43-52. [PMID: 31081587 PMCID: PMC6516085 DOI: 10.1111/dom.13630] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 12/26/2018] [Accepted: 01/02/2019] [Indexed: 12/25/2022]

Sakamoto K, Nagai M, Ebe Y, Yorimitsu H, Nishimura T. Iridium-Catalyzed Direct Hydroarylation of Glycals via C–H Activation: Ligand-Controlled Stereoselective Synthesis of α- and β-C-Glycosyl Arenes. ACS Catal 2019. [DOI: 10.1021/acscatal.8b04686] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]

Inoue MK, Matsunaga Y, Nakatsu Y, Yamamotoya T, Ueda K, Kushiyama A, Sakoda H, Fujishiro M, Ono H, Iwashita M, Sano T, Nishimura F, Morii K, Sasaki K, Masaki T, Asano T. Possible involvement of normalized Pin1 expression level and AMPK activation in the molecular mechanisms underlying renal protective effects of SGLT2 inhibitors in mice. Diabetol Metab Syndr 2019;11:57. [PMID: 31367234 PMCID: PMC6647324 DOI: 10.1186/s13098-019-0454-6] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2019] [Accepted: 07/08/2019] [Indexed: 12/19/2022] Open

Affiliation(s)

Masa-Ki Inoue Department of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551 Japan
Yasuka Matsunaga Center for Translational Research in Infection & Inflammation, School of Medicine, Tulane University, 6823 St. Charles Avenue, New Orleans, LA 70118 USA
Yusuke Nakatsu Department of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551 Japan
Takeshi Yamamotoya Department of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551 Japan
Koji Ueda Department of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551 Japan
Akifumi Kushiyama Division of Diabetes and Metabolism, The Institute for Adult Diseases, Asahi Life Foundation, Chuo-ku, Tokyo, 103-0002 Japan
Hideyuki Sakoda Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692 Japan
Midori Fujishiro Division of Diabetes and Metabolic Diseases, Nihon University School of Medicine, Itabashi, Tokyo, 173-8610 Japan
Hiraku Ono Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8670 Japan
Misaki Iwashita Section of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, Fukuoka 812-0054 Japan
Tomomi Sano Section of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, Fukuoka 812-0054 Japan
Fusanori Nishimura Section of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, Fukuoka 812-0054 Japan
Kenichi Morii Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551 Japan
Kensuke Sasaki Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551 Japan
Takao Masaki Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551 Japan
Tomoichiro Asano Department of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551 Japan

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Kuroda S, Kobashi Y, Oi T, Kawabe K, Shiozawa F, Okumura-Kitajima L, Sugisaki-Kitano M, Io F, Yamamoto K, Kakinuma H. Discovery of potent, low-absorbable sodium-dependent glucose cotransporter 1 (SGLT1) inhibitor SGL5213 for type 2 diabetes treatment. Bioorg Med Chem 2019;27:394-409. [DOI: 10.1016/j.bmc.2018.12.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 12/07/2018] [Accepted: 12/10/2018] [Indexed: 11/16/2022]

Sirois LE, Zhao MM, Lim NK, Bednarz MS, Harrison BA, Wu W. Process Development for a Locally Acting SGLT1 Inhibitor, LX2761, Utilizing sp3–sp2 Suzuki Coupling of a Benzyl Carbonate. Org Process Res Dev 2018. [DOI: 10.1021/acs.oprd.8b00325] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]

Xu G, Gaul MD, Kuo GH, Du F, Xu JZ, Wallace N, Hinke S, Kirchner T, Silva J, Huebert ND, Lee S, Murray W, Liang Y, Demarest K. Design, synthesis and biological evaluation of (2S,3R,4R,5S,6R)-5-fluoro-6-(hydroxymethyl)-2-aryltetrahydro-2H-pyran-3,4-diols as potent and orally active SGLT dual inhibitors. Bioorg Med Chem Lett 2018;28:3446-3453. [DOI: 10.1016/j.bmcl.2018.09.025] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2018] [Revised: 09/13/2018] [Accepted: 09/17/2018] [Indexed: 10/28/2022]

Cascade reactions as efficient and universal tools for construction and modification of 6-, 5-, 4- and 3-membered sulfur heterocycles of biological relevance. Tetrahedron 2018. [DOI: 10.1016/j.tet.2018.09.022] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]

Kuroda S, Kobashi Y, Oi T, Amada H, Okumura-Kitajima L, Io F, Yamamto K, Kakinuma H. Discovery of a potent, low-absorbable sodium-dependent glucose cotransporter 1 (SGLT1) inhibitor (TP0438836) for the treatment of type 2 diabetes. Bioorg Med Chem Lett 2018;28:3534-3539. [PMID: 30297284 DOI: 10.1016/j.bmcl.2018.09.035] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 09/10/2018] [Accepted: 09/27/2018] [Indexed: 11/16/2022]

Zhao X, Sun B, Zheng H, Liu J, Qian L, Wang X, Lou H. Synthesis and biological evaluation of 6-hydroxyl C-aryl glucoside derivatives as novel sodium glucose co-transporter 2 (SGLT2) inhibitors. Bioorg Med Chem Lett 2018;28:2201-2205. [DOI: 10.1016/j.bmcl.2018.04.070] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Accepted: 04/30/2018] [Indexed: 10/17/2022]

da Silva PN, da Conceição RA, do Couto Maia R, de Castro Barbosa ML. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors: a new antidiabetic drug class. MEDCHEMCOMM 2018;9:1273-1281. [PMID: 30151080 DOI: 10.1039/c8md00183a] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Accepted: 06/05/2018] [Indexed: 01/09/2023]

Kerru N, Singh-Pillay A, Awolade P, Singh P. Current anti-diabetic agents and their molecular targets: A review. Eur J Med Chem 2018;152:436-488. [PMID: 29751237 DOI: 10.1016/j.ejmech.2018.04.061] [Citation(s) in RCA: 209] [Impact Index Per Article: 29.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 04/17/2018] [Accepted: 04/30/2018] [Indexed: 12/22/2022]

Abstract

Diabetes mellitus is a medical condition characterized by the body's loss of control over blood sugar. The frequency of diagnosed cases and consequential increases in medical costs makes it a rapidly growing chronic disease that threatens human health worldwide. In addition, its unnerving statistical projections are perilous to both the economy of the nation and man's life expectancy. Type-I and type-II diabetes are the two clinical forms of diabetes mellitus. Type-II diabetes mellitus (T2DM) is illustrated by the abnormality of glucose homeostasis in the body, resulting in hyperglycemia. Although significant research attention has been devoted to the development of diabetes regimens, which demonstrates success in lowering blood glucose levels, their efficacies are unsustainable due to undesirable side effects such as weight gain and hypoglycemia. Over the years, heterocyclic scaffolds have been the basis of anti-diabetic chemotherapies; hence, in this review we consolidate the use of bioactive scaffolds, which have been evaluated for their biological response as inhibitors against their respective anti-diabetic molecular targets over the past five years (2012-2017). Our investigation reveals a diverse target set which includes; protein tyrosine phosphatase 1 B (PTP1B), dipeptidly peptidase-4 (DPP-4), free fatty acid receptors 1 (FFAR1), G protein-coupled receptors (GPCR), peroxisome proliferator activated receptor-γ (PPARγ), sodium glucose co-transporter-2 (SGLT2), α-glucosidase, aldose reductase, glycogen phosphorylase (GP), fructose-1,6-bisphosphatase (FBPase), glucagon receptor (GCGr) and phosphoenolpyruvate carboxykinase (PEPCK). This review offers a medium on which future drug design and development toward diabetes management may be modelled (i.e. optimization via structural derivatization), as many of the drug candidates highlighted show promise as an effective anti-diabetic chemotherapy.

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Recent progress of sodium-glucose transporter 2 inhibitors as potential antidiabetic agents. Future Med Chem 2018;10:1261-1276. [PMID: 29749749 DOI: 10.4155/fmc-2017-0241] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open

Samukawa Y, Mutoh M, Chen S, Mizui N. Mechanism-Based Pharmacokinetic-Pharmacodynamic Modeling of Luseogliflozin, a Sodium Glucose Co-transporter 2 Inhibitor, in Japanese Patients with Type 2 Diabetes Mellitus. Biol Pharm Bull 2018;40:1207-1218. [PMID: 28769002 DOI: 10.1248/bpb.b16-00998] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]

Samukawa Y, Haneda M, Seino Y, Sasaki T, Fukatsu A, Kubo Y, Sato Y, Sakai S. Pharmacokinetics and Pharmacodynamics of Luseogliflozin, a Selective SGLT2 Inhibitor, in Japanese Patients With Type 2 Diabetes With Mild to Severe Renal Impairment. Clin Pharmacol Drug Dev 2018;7:820-828. [PMID: 29693800 PMCID: PMC6220780 DOI: 10.1002/cpdd.456] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 02/06/2018] [Indexed: 11/15/2022]