Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Potential Therapeutic Targets for the Management of Diabetes Mellitus Type 2

Author(s): Pranav Kumar Prabhakar* and Gaber El-Saber Batiha

Volume 31, Issue 21, 2024

Published on: 21 June, 2023

Page: [3167 - 3181] Pages: 15

DOI: 10.2174/0929867330666230501172557

Price: $65

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.

Keywords: Diabetes, hyperglycemia, molecular targets, glucose homeostasis, metabolic disorders, insulin resistance.

« Previous Next »
[1]
Almasi, F.; Mohammadipanah, F. Prominent and emerging anti-diabetic molecular targets. J. Drug Target., 2021, 29(5), 491-506.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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)methyl]benzoic 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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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-spiro[isobenzofuran-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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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-diazaspiro[4.5]dec-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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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-b]pyridine derivatives as adenosine 5′-monophosphate-activated protein kinase activators. Arch. Pharm., 2019, 352(8), 1900066.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1186/s13065-019-0532-8] [PMID: 31384754]

Rights & Permissions Print Cite
Article Metrics
33
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy