Potential Therapeutic Targets for the Management of Diabetes Mellitus Type 2


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Abstract

Diabetes is one of the lifelong chronic metabolic diseases which is prevalent globally. There is a continuous rise in the number of people suffering from this disease with time. It is characterized by hyperglycemia, which leads to severe damage to the body’s system, such as blood vessels and nerves. Diabetes occurs due to the dysfunction of pancreatic β -cell which leads to the reduction in the production of insulin or body cells unable to use insulin produce efficiently. As per the data shared International diabetes federation (IDF), there are around 415 million affected by this disease worldwide. There are a number of hit targets available that can be focused on treating diabetes. There are many drugs available and still under development for the treatment of type 2 diabetes. Inhibition of gluconeogenesis, lipolysis, fatty acid oxidation, and glucokinase activator is emerging targets for type 2 diabetes treatment. Diabetes management can be supplemented with drug intervention for obesity. The antidiabetic drug sale is the second-largest in the world, trailing only that of cancer. The future of managing diabetes will be guided by research on various novel targets and the development of various therapeutic leads, such as GLP-1 agonists, DPP-IV inhibitors, and SGLT2 inhibitors that have recently completed their different phases of clinical trials. Among these therapeutic targets associated with type 2 diabetes, this review focused on some common therapeutic targets for developing novel drug candidates of the newer generation with better safety and efficacy.

About the authors

Pranav Prabhakar

Division of Research and Development, Lovely Professional University

Author for correspondence.
Email: info@benthamscience.net

Gaber Batiha

Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University

Email: info@benthamscience.net

References

  1. Almasi, F.; Mohammadipanah, F. Prominent and emerging anti-diabetic molecular targets. J. Drug Target., 2021, 29(5), 491-506. doi: 10.1080/1061186X.2020.1859517 PMID: 33336602
  2. Saeedi, P.; Petersohn, I.; Salpea, P.; Malanda, B.; Karuranga, S.; Unwin, N.; Colagiuri, S.; Guariguata, L.; Motala, A.A.; Ogurtsova, K.; Shaw, J.E.; Bright, D.; Williams, R. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res. Clin. Pract., 2019, 157, 107843. doi: 10.1016/j.diabres.2019.107843 PMID: 31518657
  3. 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. doi: 10.1016/j.ejmech.2018.04.061 PMID: 29751237
  4. Bharatam, P.; Patel, D.; Adane, L.; Mittal, A.; Sundriyal, S. Modeling and informatics in designing anti-diabetic agents. Curr. Pharm. Des., 2007, 13(34), 3518-3530. doi: 10.2174/138161207782794239 PMID: 18220788
  5. Kumar, S.; Mittal, A.; Babu, D.; Mittal, A. Herbal medicines for diabetes management and its secondary complications. Curr. Diabetes Rev., 2021, 17(4), 437-456. doi: 10.2174/18756417MTExfMTQ1z PMID: 33143632
  6. Kaur, P.; Mittal, A.; Nayak, S.K.; Vyas, M.; Mishra, V.; Khatik, G.L. Current strategies and drug targets in the management of type 2 diabetes mellitus. Curr. Drug Targets, 2018, 19(15), 1738-1766. doi: 10.2174/1389450119666180727142902 PMID: 30051787
  7. Khatik, G.L.; Datusalia, A.K.; Ahsan, W.; Kaur, P.; Vyas, M.; Mittal, A.; Nayak, S.K. A retrospect study on thiazole derivatives as the potential antidiabetic agents in drug discovery and developments. Curr. Drug Discov. Technol., 2018, 15(3), 163-177. doi: 10.2174/1570163814666170915134018 PMID: 28914188
  8. Kehinde, B.A.; Sharma, P. Recently isolated antidiabetic hydrolysates and peptides from multiple food sources: A review. Crit. Rev. Food Sci. Nutr., 2020, 60(2), 322-340. doi: 10.1080/10408398.2018.1528206 PMID: 30463420
  9. Malik, T.; Roy, P.; Abdulsalam, F.I.; Pandey, D.K.; Bhattacharjee, A.; Eruvaram, N.R. Evaluation of antioxidant, antibacterial, and antidiabetic potential of two traditional medicinal plants of India: Swertia cordata and Swertia chirayita. Pharmacognos. Res., 2015, 7(5), 57. doi: 10.4103/0974-8490.157997 PMID: 26109789
  10. Kumar, S.; Mittal, A.; Mittal, A. A review upon medicinal perspective and designing rationale of DPP-4 inhibitors. Bioorg. Med. Chem., 2021, 46, 116354. doi: 10.1016/j.bmc.2021.116354 PMID: 34428715
  11. Kaur, P.; Anuradha; Chandra, A.; Tanwar, T.; Sahu, S.K.; Mittal, A. Emerging quinoline- and quinolone-based antibiotics in the light of epidemics. Chem. Biol. Drug Des., 2022, 100(6), 765-785. doi: 10.1111/cbdd.14025 PMID: 35128812
  12. Kaur, P.; Mittal, A.; Sahu, S.K. Pharmacogenomic advancements for the management of diabetes mellitus. Eur. J. Mol. Clin. Med., 2020, 7(7), 2607-2616.
  13. Hinnen, D. Glucagon-like peptide 1 receptor agonists for type 2 diabetes. Diabet. Spectr., 2017, 30(3), 202-210. doi: 10.2337/ds16-0026 PMID: 28848315
  14. Gilbert, M.P.; Pratley, R.E. GLP-1 analogs and DPP-4 inhibitors in type 2 diabetes therapy: review of head-to-head clinical trials. Front. Endocrinol., 2020, 11, 178. doi: 10.3389/fendo.2020.00178 PMID: 32308645
  15. Jung, C.H.; Park, C.Y.; Ahn, K.J.; Kim, N.H.; Jang, H.C.; Lee, M.K.; Park, J.Y.; Chung, C.H.; Min, K.W.; Sung, Y.A.; Park, J.H.; Kim, S.J.; Lee, H.J.; Park, S.W. A randomized, double-blind, placebo-controlled, phase II clinical trial to investigate the efficacy and safety of oral DA-1229 in patients with type 2 diabetes mellitus who have inadequate glycaemic control with diet and exercise. Diabet. Metab. Res. Rev., 2015, 31(3), 295-306. doi: 10.1002/dmrr.2613 PMID: 25362864
  16. Goldenberg, R.; Gantz, I.; Andryuk, P.J.; O’Neill, E.A.; Kaufman, K.D.; Lai, E.; Wang, Y.N.; Suryawanshi, S.; Engel, S.S. Randomized clinical trial comparing the efficacy and safety of treatment with the once-weekly dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin or the once-daily DPP-4 inhibitor sitagliptin in patients with type 2 diabetes inadequately controlled on m. Diabet. Obes. Metab., 2017, 19(3), 394-400. doi: 10.1111/dom.12832 PMID: 28093853
  17. Maezaki, H.; Tawada, M.; Yamashita, T.; Banno, Y.; Miyamoto, Y.; Yamamoto, Y.; Ikedo, K.; Kosaka, T.; Tsubotani, S.; Tani, A.; Asakawa, T.; Suzuki, N.; Oi, S. Design of potent dipeptidyl peptidase IV (DPP-4) inhibitors by employing a strategy to form a salt bridge with Lys554. Bioorg. Med. Chem. Lett., 2017, 27(15), 3565-3571. doi: 10.1016/j.bmcl.2017.05.048 PMID: 28579121
  18. Wang, J.; Feng, Y.; Ji, X.; Deng, G.; Leng, Y.; Liu, H. Synthesis and biological evaluation of pyrrolidine-2-carbonitrile and 4-fluoropyrrolidine-2-carbonitrile derivatives as dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes. Bioorg. Med. Chem., 2013, 21(23), 7418-7429. doi: 10.1016/j.bmc.2013.09.048 PMID: 24153396
  19. Mohammad, S. GPR40 agonists for the treatment of type 2 diabetes mellitus: Benefits and challenges. Curr. Drug Targets, 2016, 17(11), 1292-1300. doi: 10.2174/1389450117666151209122702 PMID: 26648068
  20. Burant, C.F. Activation of GPR40 as a therapeutic target for the treatment of type 2 diabetes. Diabetes Care, 2013, 36(Suppl. 2), S175-S179. doi: 10.2337/dcS13-2037 PMID: 23882043
  21. Li, Z.; Pan, M.; Su, X.; Dai, Y.; Fu, M.; Cai, X.; Shi, W.; Huang, W.; Qian, H. Discovery of novel pyrrole-based scaffold as potent and orally bioavailable free fatty acid receptor 1 agonists for the treatment of type 2 diabetes. Bioorg. Med. Chem., 2016, 24(9), 1981-1987. doi: 10.1016/j.bmc.2016.03.014 PMID: 27020683
  22. Li, Z.; Qiu, Q.; Xu, X.; Wang, X.; Jiao, L.; Su, X.; Pan, M.; Huang, W.; Qian, H. Design, synthesis and structure–activity relationship studies of new thiazole-based free fatty acid receptor 1 agonists for the treatment of type 2 diabetes. Eur. J. Med. Chem., 2016, 113, 246-257. doi: 10.1016/j.ejmech.2016.02.040 PMID: 26945112
  23. Li, Z.; Wang, X.; Xu, X.; Yang, J.; Qiu, Q.; Qiang, H.; Huang, W.; Qian, H. Design, synthesis and structure–activity relationship studies of novel phenoxyacetamide-based free fatty acid receptor 1 agonists for the treatment of type 2 diabetes. Bioorg. Med. Chem., 2015, 23(20), 6666-6672. doi: 10.1016/j.bmc.2015.09.010 PMID: 26420383
  24. Sharma, S.; Mittal, A.; Kumar, S. Structural perspectives and advancement of sglt2 inhibitors for the treatment of type 2 diabetes. Curr. Diabetes Rev., 2021. PMID: 34538233
  25. Bhimanwar, R.S.; Mittal, A. TGR5 agonists for diabetes treatment: A patent review and clinical advancements (2012-present). Expert Opin. Ther. Pat., 2022, 32(2), 191-209. doi: 10.1080/13543776.2022.1994551 PMID: 34652989
  26. Kumar, S.; Khatik, G.L.; Mittal, A. Recent developments in sodium-glucose co-transporter 2 (SGLT2) inhibitors as a valuable tool in the treatment of type 2 diabetes mellitus. Mini Rev. Med. Chem., 2020, 20(3), 170-182. doi: 10.2174/1389557519666191009163519 PMID: 32134370
  27. Chandra, A.; Kaur, P.; Sahu, S.K.; Mittal, A. A new insight into the treatment of diabetes by means of pan PPAR agonists. Chem. Biol. Drug Des., 2022, 100(6), 947-967. doi: 10.1111/cbdd.14020 PMID: 34990085
  28. Kumar, S.; Khatik, G.L.; Mittal, A. In silico molecular docking study to search new SGLT2 inhibitor based on dioxabicyclo 3.2. 1 octane scaffold. Curr. Computeraided Drug Des., 2020, 16(2), 145-154. doi: 10.2174/1573409914666181019165821 PMID: 30345926
  29. Plodkowski, R.A.; McGarvey, M.E.; Huribal, H.M.; Reisinger-Kindle, K.; Kramer, B.; Solomon, M.; Nguyen, Q.T. SGLT2 inhibitors for type 2 diabetes mellitus treatment. Fed. Pract., 2015, 32(S11), 8S-15S. PMID: 30766102
  30. Hsia, D.S.; Grove, O.; Cefalu, W.T. An update on SGLT2 inhibitors for the treatment of diabetes mellitus. Curr. Opin. Endocrinol. Diabetes Obes., 2017, 24(1), 73. PMID: 27898586
  31. Ohtake, Y.; Sato, T.; Matsuoka, H.; Nishimoto, M.; Taka, N.; Takano, K.; Yamamoto, K.; Ohmori, M.; Higuchi, T.; Murakata, M.; Kobayashi, T.; Morikawa, K.; Shimma, N.; Suzuki, M.; Hagita, H.; Ozawa, K.; Yamaguchi, K.; Kato, M.; Ikeda, S. 5a-Carba-β-d-glucopyranose derivatives as novel sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes. Bioorg. Med. Chem., 2011, 19(18), 5334-5341. doi: 10.1016/j.bmc.2011.08.005 PMID: 21873071
  32. Pan, X.; Huan, Y.; Shen, Z.; Liu, Z. Synthesis and biological evaluation of novel tetrahydroisoquinoline- C -aryl glucosides as SGLT2 inhibitors for the treatment of type 2 diabetes. Eur. J. Med. Chem., 2016, 114, 89-100. doi: 10.1016/j.ejmech.2016.02.053 PMID: 26974378
  33. Yao, C.H.; Song, J.S.; Chen, C.T.; Yeh, T.K.; Hsieh, T.C.; Wu, S.H.; Huang, C.Y.; Huang, Y.L.; Wang, M.H.; Liu, Y.W.; Tsai, C.H.; Kumar, C.R.; Lee, J.C. Synthesis and biological evaluation of novel C-indolylxylosides as sodium-dependent glucose co-transporter 2 inhibitors. Eur. J. Med. Chem., 2012, 55, 32-38. doi: 10.1016/j.ejmech.2012.06.053 PMID: 22818040
  34. Go, Y.; Jeong, J.Y.; Jeoung, N.H.; Jeon, J.H.; Park, B.Y.; Kang, H.J.; Ha, C.M.; Choi, Y.K.; Lee, S.J.; Ham, H.J.; Kim, B.G.; Park, K.G.; Park, S.Y.; Lee, C.H.; Choi, C.S.; Park, T.S.; Lee, W.N.P.; Harris, R.A.; Lee, I.K. Inhibition of pyruvate dehydrogenase kinase 2 protects against hepatic steatosis through modulation of tricarboxylic acid cycle anaplerosis and ketogenesis. Diabetes, 2016, 65(10), 2876-2887. doi: 10.2337/db16-0223 PMID: 27385159
  35. Johnson, T.O.; Ermolieff, J.; Jirousek, M.R. Protein tyrosine phosphatase 1B inhibitors for diabetes. Nat. Rev. Drug Discov., 2002, 1(9), 696-709. doi: 10.1038/nrd895 PMID: 12209150
  36. Tian, S.; Zhao, H.; Song, H. Shared signaling pathways and targeted therapy by natural bioactive compounds for obesity and type 2 diabetes. Crit. Rev. Food Sci. Nutr., 2022, 17, 1-18. doi: 10.1080/10408398.2022.2148090 PMID: 36397728
  37. Tso, S.C.; Lou, M.; Wu, C.Y.; Gui, W.J.; Chuang, J.L.; Morlock, L.K.; Williams, N.S.; Wynn, R.M.; Qi, X.; Chuang, D.T. Development of dihydroxyphenyl sulfonylisoindoline derivatives as liver-targeting pyruvate dehydrogenase kinase inhibitors. J. Med. Chem., 2017, 60(3), 1142-1150. doi: 10.1021/acs.jmedchem.6b01540 PMID: 28085286
  38. Bourebaba, L.; Łyczko, J.; Alicka, M.; Bourebaba, N.; Szumny, A.; Fal, A.; Marycz, K. Inhibition of protein-tyrosine phosphatase PTP1B and LMPTP promotes palmitate/oleate-challenged HepG2 cell survival by reducing lipoapoptosis, improving mitochondrial dynamics and mitigating oxidative and endoplasmic reticulum stress. J. Clin. Med., 2020, 9(5), 1294. doi: 10.3390/jcm9051294 PMID: 32369900
  39. Zhang, R.; Yu, R.; Xu, Q.; Li, X.; Luo, J.; Jiang, B.; Wang, L.; Guo, S.; Wu, N.; Shi, D. Discovery and evaluation of the hybrid of bromophenol and saccharide as potent and selective protein tyrosine phosphatase 1B inhibitors. Eur. J. Med. Chem., 2017, 134, 24-33. doi: 10.1016/j.ejmech.2017.04.004 PMID: 28395151
  40. Singh, S.; Singh Grewal, A.; Grover, R.; Sharma, N.; Chopra, B.; Kumar Dhingra, A.; Arora, S.; Redhu, S.; Lather, V. Recent updates on development of protein-tyrosine phosphatase 1B inhibitors for treatment of diabetes, obesity and related disorders. Bioorg. Chem., 2022, 121, 105626. doi: 10.1016/j.bioorg.2022.105626 PMID: 35255350
  41. Yamazaki, H.; Kanno, S.; Abdjul, D.B.; Namikoshi, M. A bromopyrrole-containing diterpene alkaloid from the Okinawan marine sponge Agelas nakamurai activates the insulin pathway in Huh-7 human hepatoma cells by inhibiting protein tyrosine phosphatase 1B. Bioorg. Med. Chem. Lett., 2017, 27(10), 2207-2209. doi: 10.1016/j.bmcl.2017.03.033 PMID: 28389151
  42. Ottanà, R.; Paoli, P.; Naß, A.; Lori, G.; Cardile, V.; Adornato, I.; Rotondo, A.; Graziano, A.C.E.; Wolber, G.; Maccari, R. Discovery of 4-(5-arylidene-4-oxothiazolidin-3-yl)methylbenzoic acid derivatives active as novel potent allosteric inhibitors of protein tyrosine phosphatase 1B: in silico studies and in vitro evaluation as insulinomimetic and anti-inflammatory agents. Eur. J. Med. Chem., 2017, 127, 840-858. doi: 10.1016/j.ejmech.2016.10.063 PMID: 27842892
  43. Ye, D.; Wang, Y.; Li, H.; Jia, W.; Man, K.; Lo, C.M.; Wang, Y.; Lam, K.S.L.; Xu, A. Fibroblast growth factor 21 protects against acetaminophen-induced hepatotoxicity by potentiating peroxisome proliferator-activated receptor coactivator protein-1α-mediated antioxidant capacity in mice. Hepatology, 2014, 60(3), 977-989. doi: 10.1002/hep.27060 PMID: 24590984
  44. Tang, M.; Su, J.; Xu, T.; Wang, X.; Zhang, D.; Wang, X. Serum fibroblast growth factor 19 and endogenous islet beta cell function in type 2 diabetic patients. Diabetol. Metab. Syndr., 2019, 11(1), 79. doi: 10.1186/s13098-019-0475-1 PMID: 31572498
  45. Mo, C.; Zhang, Z.; Guise, C.P.; Li, X.; Luo, J.; Tu, Z.; Xu, Y.; Patterson, A.V.; Smaill, J.B.; Ren, X.; Lu, X.; Ding, K. 2-Aminopyrimidine derivatives as new selective fibroblast growth factor receptor 4 (FGFR4) inhibitors. ACS Med. Chem. Lett., 2017, 8(5), 543-548. doi: 10.1021/acsmedchemlett.7b00091 PMID: 28523108
  46. Hughes, K.A.; Webster, S.P.; Walker, B.R. 11-Beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors in Type 2 diabetes mellitus and obesity. Expert Opin. Investig. Drugs, 2008, 17(4), 481-496. doi: 10.1517/13543784.17.4.481 PMID: 18363514
  47. Zhang, C.; Xu, M.; He, C.; Zhuo, J.; Burns, D.M.; Qian, D.Q.; Lin, Q.; Li, Y.L.; Chen, L.; Shi, E.; Agrios, C.; Weng, L.; Sharief, V.; Jalluri, R.; Li, Y.; Scherle, P.; Diamond, S.; Hunter, D.; Covington, M.; Marando, C.; Wynn, R.; Katiyar, K.; Contel, N.; Vaddi, K.; Yeleswaram, S.; Hollis, G.; Huber, R.; Friedman, S.; Metcalf, B.; Yao, W. Discovery of 1′-(1-phenylcyclopropane-carbonyl)-3H-spiroisobenzofuran-1,3′-pyrrolidin-3-one as a novel steroid mimetic scaffold for the potent and tissue-specific inhibition of 11β-HSD1 using a scaffold-hopping approach. Bioorg. Med. Chem. Lett., 2022, 69, 128782. doi: 10.1016/j.bmcl.2022.128782 PMID: 35537608
  48. Scott, J.S.; Goldberg, F.W.; Turnbull, A.V. Medicinal chemistry of inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). J. Med. Chem., 2014, 57(11), 4466-4486. doi: 10.1021/jm4014746 PMID: 24294985
  49. Chang, Y.H.; Hung, H.Y. Recent advances in natural antiobesity compounds and derivatives based on in vivo evidence: A mini-review. Eur. J. Med. Chem., 2022, 237, 114405. doi: 10.1016/j.ejmech.2022.114405 PMID: 35489224
  50. Sato, K.; Takahagi, H.; Yoshikawa, T.; Morimoto, S.; Takai, T.; Hidaka, K.; Kamaura, M.; Kubo, O.; Adachi, R.; Ishii, T.; Maki, T.; Mochida, T.; Takekawa, S.; Nakakariya, M.; Amano, N.; Kitazaki, T. Discovery of a novel series of N-phenylindoline-5-sulfonamide derivatives as potent, selective, and orally bioavailable acyl CoA: monoacylglycerol acyltransferase-2 inhibitors. J. Med. Chem., 2015, 58(9), 3892-3909. doi: 10.1021/acs.jmedchem.5b00178 PMID: 25897973
  51. Hong, D.J.; Jung, S.H.; Kim, J.; Jung, D.; Ahn, Y.G.; Suh, K.H.; Min, K.H. Synthesis and biological evaluation of novel thienopyrimidine derivatives as diacylglycerol acyltransferase 1 (DGAT-1) inhibitors. J. Enzyme Inhib. Med. Chem., 2020, 35(1), 227-234. doi: 10.1080/14756366.2019.1693555 PMID: 31752563
  52. DeMong, D.; Dai, X.; Hwa, J.; Miller, M.; Lin, S.I.; Kang, L.; Stamford, A.; Greenlee, W.; Yu, W.; Wong, M.; Lavey, B.; Kozlowski, J.; Zhou, G.; Yang, D.Y.; Patel, B.; Soriano, A.; Zhai, Y.; Sondey, C.; Zhang, H.; Lachowicz, J.; Grotz, D.; Cox, K.; Morrison, R.; Andreani, T.; Cao, Y.; Liang, M.; Meng, T.; McNamara, P.; Wong, J.; Bradley, P.; Feng, K.I.; Belani, J.; Chen, P.; Dai, P.; Gauuan, J.; Lin, P.; Zhao, H. The Discovery of N -((2 H -Tetrazol-5-yl)methyl)-4-((R)-1-((5 r, 8 R)-8-(tert -butyl)-3-(3,5-dichlorophenyl)-2-oxo-1,4-diazaspiro4.5dec-3-en-1-yl)-4,4-dimethylpentyl)benzamide (SCH 900822): A potent and selective glucagon receptor antagonist. J. Med. Chem., 2014, 57(6), 2601-2610. doi: 10.1021/jm401858f PMID: 24527772
  53. Toulis, K.A.; Hanif, W.; Saravanan, P.; Willis, B.H.; Marshall, T.; Kumarendran, B.; Gokhale, K.; Ghosh, S.; Cheng, K.K.; Narendran, P.; Thomas, G.N.; Nirantharakumar, K. All-cause mortality in patients with diabetes under glucagon-like peptide-1 agonists: A population-based, open cohort study. Diabetes Metab., 2017, 43(3), 211-216. doi: 10.1016/j.diabet.2017.02.003 PMID: 28325589
  54. van Poelje, P.D.; Potter, S.C.; Chandramouli, V.C.; Landau, B.R.; Dang, Q.; Erion, M.D. Inhibition of fructose 1,6-bisphosphatase reduces excessive endogenous glucose production and attenuates hyperglycemia in Zucker diabetic fatty rats. Diabetes, 2006, 55(6), 1747-1754. doi: 10.2337/db05-1443 PMID: 16731838
  55. Kaur, R.; Dahiya, L.; Kumar, M. Fructose-1,6-bisphosphatase inhibitors: A new valid approach for management of type 2 diabetes mellitus. Eur. J. Med. Chem., 2017, 141, 473-505. doi: 10.1016/j.ejmech.2017.09.029 PMID: 29055870
  56. Bie, J.; Liu, S.; Li, Z.; Mu, Y.; Xu, B.; Shen, Z. Discovery of novel indole derivatives as allosteric inhibitors of fructose-1,6-bisphosphatase. Eur. J. Med. Chem., 2015, 90, 394-405. doi: 10.1016/j.ejmech.2014.11.049 PMID: 25461330
  57. Bie, J.; Liu, S.; Zhou, J.; Xu, B.; Shen, Z. Design, synthesis and biological evaluation of 7-nitro-1H-indole-2-carboxylic acid derivatives as allosteric inhibitors of fructose-1,6-bisphosphatase. Bioorg. Med. Chem., 2014, 22(6), 1850-1862. doi: 10.1016/j.bmc.2014.01.047 PMID: 24530031
  58. Liao, B.R.; He, H.B.; Yang, L.L.; Gao, L.X.; Chang, L.; Tang, J.; Li, J.Y.; Li, J.; Yang, F. Synthesis and structure–activity relationship of non-phosphorus-based fructose-1,6-bisphosphatase inhibitors: 2,5-Diphenyl-1,3,4-oxadiazoles. Eur. J. Med. Chem., 2014, 83, 15-25. doi: 10.1016/j.ejmech.2014.06.011 PMID: 24946215
  59. Authier, F.; Desbuquois, B. Glucagon receptors. Cell. Mol. Life Sci., 2008, 65(12), 1880-1899. doi: 10.1007/s00018-008-7479-6 PMID: 18292967
  60. Takagi, H.; Tanimoto, K.; Shimazaki, A.; Tonomura, Y.; Momosaki, S.; Sakamoto, S.; Abe, K.; Notoya, M.; Yukioka, H. A novel acetyl-CoA carboxylase 2 selective inhibitor improves whole-body insulin resistance and hyperglycemia in diabetic mice through target-dependent pathways. J. Pharmacol. Exp. Ther., 2020, 372(3), 256-263. doi: 10.1124/jpet.119.263590 PMID: 31900320
  61. Abu-Elheiga, L.; Wu, H.; Gu, Z.; Bressler, R.; Wakil, S.J. Acetyl-CoA carboxylase 2-/- mutant mice are protected against fatty liver under high-fat, high-carbohydrate dietary and de novo lipogenic conditions. J. Biol. Chem., 2012, 287(15), 12578-12588. doi: 10.1074/jbc.M111.309559 PMID: 22362781
  62. Duran-Sandoval, D.; Mautino, G.; Martin, G.; Percevault, F.; Barbier, O.; Fruchart, J.C.; Kuipers, F.; Staels, B. Glucose regulates the expression of the farnesoid X receptor in liver. Diabetes, 2004, 53(4), 890-898. doi: 10.2337/diabetes.53.4.890 PMID: 15047603
  63. Ma, K.; Saha, P.K.; Chan, L.; Moore, D.D. Farnesoid X receptor is essential for normal glucose homeostasis. J. Clin. Invest., 2006, 116(4), 1102-1109. doi: 10.1172/JCI25604 PMID: 16557297
  64. Baker, D.J.; Timmons, J.A.; Greenhaff, P.L. Glycogen phosphorylase inhibition in type 2 diabetes therapy: a systematic evaluation of metabolic and functional effects in rat skeletal muscle. Diabetes, 2005, 54(8), 2453-2459. doi: 10.2337/diabetes.54.8.2453 PMID: 16046314
  65. Toulis, K.A.; Nirantharakumar, K.; Pourzitaki, C.; Barnett, A.H.; Tahrani, A.A. Glucokinase activators for type 2 diabetes: Challenges and future developments. Drugs, 2020, 80(5), 467-475. doi: 10.1007/s40265-020-01278-z PMID: 32162273
  66. Schweiker, S.S.; Loughlin, W.A.; Lohning, A.S.; Petersson, M.J.; Jenkins, I.D. Synthesis, screening and docking of small heterocycles as glycogen phosphorylase inhibitors. Eur. J. Med. Chem., 2014, 84, 584-594. doi: 10.1016/j.ejmech.2014.07.063 PMID: 25062009
  67. Zhang, L.; Chen, X.; Liu, J.; Zhu, Q.; Leng, Y.; Luo, X.; Jiang, H.; Liu, H. Discovery of novel dual-action antidiabetic agents that inhibit glycogen phosphorylase and activate glucokinase. Eur. J. Med. Chem., 2012, 58, 624-639. doi: 10.1016/j.ejmech.2012.06.020 PMID: 23178962
  68. Loughlin, W.A.; Jenkins, I.D.; Karis, N.D.; Schweiker, S.S.; Healy, P.C. 2-Oxo-1,2-dihydropyridinyl-3-yl amide-based GPa inhibitors: Design, synthesis and structure-activity relationship study. Eur. J. Med. Chem., 2016, 111, 1-14. doi: 10.1016/j.ejmech.2016.01.031 PMID: 26851835
  69. Banerjee, M.; Khursheed, R.; Yadav, A.K.; Singh, S.K.; Gulati, M.; Pandey, D.K.; Prabhakar, P.K.; Kumar, R.; Porwal, O.; Awasthi, A.; Kumari, Y.; Kaur, G.; Ayinkamiye, C.; Prashar, R.; Mankotia, D.; Pandey, N.K. A systematic review on synthetic drugs and phytopharmaceuticals used to manage diabetes. Curr. Diabetes Rev., 2020, 16(4), 340-356. doi: 10.2174/1573399815666190822165141 PMID: 31438829
  70. Prabhakar, PK; Mukesh, D Mechanism of action of medicinal plants towards diabetes mellitus-a review. Phytopharmacology and therapeutic values IV., 2008, 181-204.
  71. Hussain, K. Mutations in pancreatic ß-cell Glucokinase as a cause of hyperinsulinaemic hypoglycaemia and neonatal diabetes mellitus. Rev. Endocr. Metab. Disord., 2010, 11(3), 179-183. doi: 10.1007/s11154-010-9147-z PMID: 20878480
  72. Zheng, B.; Peng, Y.; Wu, W.; Ma, J.; Zhang, Y.; Guo, Y.; Sun, S.; Chen, Z.; Li, Q.; Hu, G. Synthesis and structure–activity relationships of pyrazolo-3,4-bpyridine derivatives as adenosine 5′-monophosphate-activated protein kinase activators. Arch. Pharm., 2019, 352(8), 1900066. doi: 10.1002/ardp.201900066 PMID: 31373047
  73. Prabhakar, P.K.; Doble, M. Mechanism of action of natural products used in the treatment of diabetes mellitus. Chin. J. Integr. Med., 2011, 17(8), 563-574. doi: 10.1007/s11655-011-0810-3 PMID: 21826590
  74. Prabhakar, P.; Doble, M. A target based therapeutic approach towards diabetes mellitus using medicinal plants. Curr. Diabetes Rev., 2008, 4(4), 291-308. doi: 10.2174/157339908786241124 PMID: 18991598
  75. Prabhakar, P.K.; Sivakumar, P.M. Protein tyrosine phosphatase 1B inhibitors: A novel therapeutic strategy for the management of type 2 diabetes mellitus. Curr. Pharm. Des., 2019, 25(23), 2526-2539. doi: 10.2174/1381612825666190716102901 PMID: 31333090
  76. Matschinsky, F.M.; Zelent, B.; Doliba, N.; Li, C.; Vanderkooi, J.M.; Naji, A.; Sarabu, R.; Grimsby, J. Glucokinase activators for diabetes therapy: May 2010 status report. Diabetes Care, 2011, 34(S2), S236-S243. doi: 10.2337/dc11-s236 PMID: 21525462
  77. Khadse, S.C.; Amnerkar, N.D.; Dighole, K.S.; Dhote, A.M.; Patil, V.R.; Lokwani, D.K.; Ugale, V.G.; Charbe, N.B.; Chatpalliwar, V.A. Hetero-substituted sulfonamido-benzamide hybrids as glucokinase activators: Design, synthesis, molecular docking and in silico ADME evaluation. J. Mol. Struct., 2020, 1222, 128916. doi: 10.1016/j.molstruc.2020.128916
  78. Grewal, A.S.; Kharb, R.; Prasad, D.N.; Dua, J.S.; Lather, V. Design, synthesis and evaluation of novel 3,5-disubstituted benzamide derivatives as allosteric glucokinase activators. BMC Chem., 2019, 13(1), 2. doi: 10.1186/s13065-019-0532-8 PMID: 31384754

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