FFAR4/GPR120 SEBAGAI TARGET DESAIN DAN PENGEMBANGAN OBAT DIABETES MELITUS TIPE 2 IN SILICO: SUATU TINJAUAN DAN PERSPEKTIF
-
FREDY Z. SAUDALE(1*)
-
MERVINA B. TOKAN(2)
-
STEVEN Y. LEO(3)
-
SERLY P. ATI(4)
(*) Corresponding Author
Keywords:
FFAR4/GPR120, diabetes type 2, agonist, modelling
Abstract
FFAR4/GPR120 is an attractive membrane protein for diabetic drug design. Crystal structure of GPCR membrane proteins is difficult to obtain. Most of GPCR proteins lack experimental 3D structures. Therefore, computational method (in silico) using comparative homology modelling has been widely applied to solve it. To develop FFAR4/GPR120 selective compounds with high specificity, homology modelling of FFAR4/GPR120 can be constructed by utilizing other known GPCR crystal structures. This review article surveys the recent developments in the application of computational approaches in searching for selective agonist ligands and provides a perspective on computational approaches to the development of new drugs targeting FFAR4/GPR120.
Downloads
Download data is not yet available.
References
1. Roemling, C.; Qaim, M. Obesity Trends and Determinants in Indonesia. Appetite 2012, 58 (3), 1005–1013.
2. Usfar, A. A.; Lebenthal, E.; Achadi, E.; Hadi, H. Obesity as a Poverty-Related Emerging Nutrition Problems: The Case of Indonesia. Obes. Rev. 2010, 11 (12), 924–928.
3. Al-Goblan, A. S.; Al-Alfi, M. A.; Khan, M. Z. Mechanism Linking Diabetes Mellitus and Obesity. Diabetes Metab. Syndr. Obes. Targets Ther. 2014, 7, 587–591. https://doi.org/10.2147/DMSO.S67400.
4. Dandona, P.; Aljada, A.; Chaudhuri, A.; Mohanty, P.; Garg, R. Metabolic Syndrome: A Comprehensive Perspective Based on Interactions between Obesity, Diabetes, and Inflammation. Circulation 2005, 111 (11), 1448–1454.
5. Golay, A.; Ybarra, J. Link between Obesity and Type 2 Diabetes. Best Pract. Res. Clin. Endocrinol. Metab. 2005, 19 (4), 649–663.
6. Roglic, G. WHO Global Report on Diabetes: A Summary. Int. J. Noncommunicable Dis. 2016, 1 (1), 3.
7. Czech, M. P. Insulin Action and Resistance in Obesity and Type 2 Diabetes. Nat. Med. 2017, 23 (7), 804–814.
8. Guariguata, L.; Whiting, D. R.; Hambleton, I.; Beagley, J.; Linnenkamp, U.; Shaw, J. E. Global Estimates of Diabetes Prevalence for 2013 and Projections for 2035. Diabetes Res. Clin. Pract. 2014, 103 (2), 137–149.
9. Soewondo, P.; Soegondo, S.; Suastika, K.; Pranoto, A.; Soeatmadji, D. W.; Tjokroprawiro, A. The DiabCare Asia 2008 Study–Outcomes on Control and Complications of Type 2 Diabetic Patients in Indonesia. Med. J. Indones. 2010, 19 (4), 235–44.
10. Azimova, K.; San Juan, Z.; Mukherjee, D. Cardiovascular Safety Profile of Currently Available Diabetic Drugs. Ochsner J. 2014, 14 (4), 616–632.
11. Scheen, A. Thiazolidinediones and Liver Toxicity. Diabetes Metab. 2001, 27 (3), 305–13.
12. Bouchoucha, M.; Uzzan, B.; Cohen, R. Metformin and Digestive Disorders. Diabetes Metab. 2011, 37 (2), 90–96.
13. Richter, B.; Bandeira-Echtler, E.; Bergerhoff, K.; Lerch, C. Dipeptidyl Peptidase-4 (DPP-4) Inhibitors for Type 2 Diabetes Mellitus. Cochrane Database Syst. Rev. 2008, No. 2.
14. Rosenstock, J.; Ferrannini, E. Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, and Preventable Safety Concern with SGLT2 Inhibitors. Diabetes Care 2015, 38 (9), 1638–1642.
15. Association, A. D. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2013, 36 (Supplement 1), S67–S74.
16. Stein, S. A.; Lamos, E. M.; Davis, S. N. A Review of the Efficacy and Safety of Oral Antidiabetic Drugs. Expert Opin. Drug Saf. 2013, 12 (2), 153–175.
17. Goodarzi, M. O.; Bryer-Ash, M. Metformin Revisited: Re-Evaluation of Its Properties and Role in the Pharmacopoeia of Modern Antidiabetic Agents. Diabetes Obes. Metab. 2005, 7 (6), 654–665.
18. Amini, F. G.; Rafieian-Kopaei, M.; Nematbakhsh, M.; Baradaran, A.; Nasri, H. Ameliorative Effects of Metformin on Renal Histologic and Biochemical Alterations of Gentamicin-Induced Renal Toxicity in Wistar Rats. J. Res. Med. Sci. Off. J. Isfahan Univ. Med. Sci. 2012, 17 (7), 621.
19. Liu, K. W.; Dai, L. K.; Jean, W. Metformin-Related Vitamin B12 Deficiency. Age Ageing 2006, 35 (2), 200–201.
20. Natali, A.; Ferrannini, E. Effects of Metformin and Thiazolidinediones on Suppression of Hepatic Glucose Production and Stimulation of Glucose Uptake in Type 2 Diabetes: A Systematic Review. Diabetologia 2006, 49 (3), 434–441.
21. Lago, R. M.; Singh, P. P.; Nesto, R. W. Congestive Heart Failure and Cardiovascular Death in Patients with Prediabetes and Type 2 Diabetes given Thiazolidinediones: A Meta-Analysis of Randomised Clinical Trials. The Lancet 2007, 370 (9593), 1129–1136.
22. Karagiannis, T.; Paschos, P.; Paletas, K.; Matthews, D. R.; Tsapas, A. Dipeptidyl Peptidase-4 Inhibitors for Treatment of Type 2 Diabetes Mellitus in the Clinical Setting: Systematic Review and Meta-Analysis. Bmj 2012, 344, e1369.
23. Hauser, A. S.; Attwood, M. M.; Rask-Andersen, M.; Schiöth, H. B.; Gloriam, D. E. Trends in GPCR Drug Discovery: New Agents, Targets and Indications. Nat. Rev. Drug Discov. 2017, 16 (12), 829.
24. Andrews, S. P.; Brown, G. A.; Christopher, J. A. Structure-Based and Fragment-Based GPCR Drug Discovery. ChemMedChem 2014, 9 (2), 256–275.
25. Liu, H.-D.; Wang, W.; Xu, Z.; Liu, C.; He, D.; Du, L.-P.; Li, M.-Y.; Yu, X.; Sun, J. FFA4 Receptor (GPR120): A Hot Target for the Development of Anti-Diabetic Therapies. Eur. J. Pharmacol. 2015, 763, 160–168.
26. Brown, A. J.; Jupe, S.; Briscoe, C. P. A Family of Fatty Acid Binding Receptors. DNA Cell Biol. 2005, 24 (1), 54–61.
27. Hara, T.; Kashihara, D.; Ichimura, A.; Kimura, I.; Tsujimoto, G.; Hirasawa, A. Role of Free Fatty Acid Receptors in the Regulation of Energy Metabolism. Biochim. Biophys. Acta BBA-Mol. Cell Biol. Lipids 2014, 1841 (9), 1292–1300.
28. Fredriksson, R.; Höglund, P. J.; Gloriam, D. E.; Lagerström, M. C.; Schiöth, H. B. Seven Evolutionarily Conserved Human Rhodopsin G Protein-Coupled Receptors Lacking Close Relatives. FEBS Lett. 2003, 554 (3), 381–388.
29. Ichimura, A.; Hirasawa, A.; Hara, T.; Tsujimoto, G. Free Fatty Acid Receptors Act as Nutrient Sensors to Regulate Energy Homeostasis. Prostaglandins Other Lipid Mediat. 2009, 89 (3–4), 82–88.
30. Miyamoto, J.; Hasegawa, S.; Kasubuchi, M.; Ichimura, A.; Nakajima, A.; Kimura, I. Nutritional Signaling via Free Fatty Acid Receptors. Int. J. Mol. Sci. 2016, 17 (4), 450.
31. Olefsky, J. M. Omega 3 Fatty Acids and GPR120. Cell Metab. 2012, 15 (5), 564–565.
32. Talukdar, S.; Bae, E. J.; Imamura, T.; Morinaga, H.; Fan, W.; Li, P.; Lu, W. J.; Watkins, S. M.; Olefsky, J. M. GPR120 Is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-Inflammatory and Insulin-Sensitizing Effects. Cell 2010, 142 (5), 687–698.
33. Li, A.; Li, Y.; Du, L. Biological Characteristics and Agonists of GPR120 (FFAR4) Receptor: The Present Status of Research. Future Med. Chem. 2015, 7 (11), 1457–1468.
34. Briscoe, C. P.; Peat, A. J.; McKeown, S. C.; Corbett, D. F.; Goetz, A. S.; Littleton, T. R.; McCoy, D. C.; Kenakin, T. P.; Andrews, J. L.; Ammala, C. Pharmacological Regulation of Insulin Secretion in MIN6 Cells through the Fatty Acid Receptor GPR40: Identification of Agonist and Antagonist Small Molecules. Br. J. Pharmacol. 2006, 148 (5), 619–628.
35. Shimpukade, B.; Hudson, B. D.; Hovgaard, C. K.; Milligan, G.; Ulven, T. Discovery of a Potent and Selective GPR120 Agonist. J. Med. Chem. 2012, 55 (9), 4511–4515.
36. Halder, S.; Kumar, S.; Sharma, R. The Therapeutic Potential of GPR120: A Patent Review. Expert Opin. Ther. Pat. 2013, 23 (12), 1581–1590.
37. Zhang, D.; Leung, P. S. Potential Roles of GPR120 and Its Agonists in the Management of Diabetes. Drug Des. Devel. Ther. 2014, 8, 1013.
38. Hudson, B. D.; Shimpukade, B.; Mackenzie, A. E.; Butcher, A. J.; Pediani, J. D.; Christiansen, E.; Heathcote, H.; Tobin, A. B.; Ulven, T.; Milligan, G. The Pharmacology of TUG-891, a Potent and Selective Agonist of the Free Fatty Acid Receptor 4 (FFA4/GPR120), Demonstrates Both Potential Opportunity and Possible Challenges to Therapeutic Agonism. Mol. Pharmacol. 2013, 84 (5), 710–725.
39. Schilperoort, M.; van Dam, A. D.; Hoeke, G.; Shabalina, I. G.; Okolo, A.; Hanyaloglu, A. C.; Dib, L. H.; Mol, I. M.; Caengprasath, N.; Chan, Y.-W. The GPR120 Agonist TUG-891 Promotes Metabolic Health by Stimulating Mitochondrial Respiration in Brown Fat. EMBO Mol. Med. 2018, 10 (3).
40. Sparks, S. M.; Chen, G.; Collins, J. L.; Danger, D.; Dock, S. T.; Jayawickreme, C.; Jenkinson, S.; Laudeman, C.; Leesnitzer, M. A.; Liang, X. Identification of Diarylsulfonamides as Agonists of the Free Fatty Acid Receptor 4 (FFA4/GPR120). Bioorg. Med. Chem. Lett. 2014, 24 (14), 3100–3103.
41. Bruno, A.; Aiello, F.; Costantino, G.; Radi, M. Homology Modeling, Validation and Dynamics of the G Protein-Coupled Estrogen Receptor 1 (GPER-1). Mol. Inform. 2016, 35 (8–9), 333–339.
42. França, T. C. C. Homology Modeling: An Important Tool for the Drug Discovery. J. Biomol. Struct. Dyn. 2015, 33 (8), 1780–1793.
43. Nero, T. L.; Parker, M. W.; Morton, C. J. Protein Structure and Computational Drug Discovery. Biochem. Soc. Trans. 2018, 46 (5), 1367–1379. https://doi.org/10.1042/BST20180202.
44. Macalino, S. J. Y.; Gosu, V.; Hong, S.; Choi, S. Role of Computer-Aided Drug Design in Modern Drug Discovery. Arch. Pharm. Res. 2015, 38 (9), 1686–1701.
45. Davis, A. M.; Teague, S. J.; Kleywegt, G. J. Application and Limitations of X-Ray Crystallographic Data in Structure-Based Ligand and Drug Design. Angew. Chem. Int. Ed. 2003, 42 (24), 2718–2736.
46. Webb, B.; Sali, A. Protein Structure Modeling with MODELLER. In Functional Genomics; Springer, 2017; pp 39–54.
47. Schwede, T.; Kopp, J.; Guex, N.; Peitsch, M. C. SWISS-MODEL: An Automated Protein Homology-Modeling Server. Nucleic Acids Res. 2003, 31 (13), 3381–3385.
48. Kelley, L. A.; Mezulis, S.; Yates, C. M.; Wass, M. N.; Sternberg, M. J. E. The Phyre2 Web Portal for Protein Modeling, Prediction and Analysis. Nat. Protoc. 2015, 10 (6), 845–858. https://doi.org/10.1038/nprot.2015.053.
49. Yang, J.; Zhang, Y. I-TASSER Server: New Development for Protein Structure and Function Predictions. Nucleic Acids Res. 2015, 43 (W1), W174–W181.
50. Lybrand, T. P. Ligand—Protein Docking and Rational Drug Design. Curr. Opin. Struct. Biol. 1995, 5 (2), 224–228.
51. Khan, S. U.; Ahemad, N.; Chuah, L.-H.; Naidu, R.; Htar, T. T. Sequential Ligand-and Structure-Based Virtual Screening Approach for the Identification of Potential G Protein-Coupled Estrogen Receptor-1 (GPER-1) Modulators. RSC Adv. 2019, 9 (5), 2525–2538.
52. Jacob, R. B.; Andersen, T.; McDougal, O. M. Accessible High-Throughput Virtual Screening Molecular Docking Software for Students and Educators. PLoS Comput. Biol. 2012, 8 (5), e1002499.
53. Gaulton, A.; Bellis, L. J.; Bento, A. P.; Chambers, J.; Davies, M.; Hersey, A.; Light, Y.; McGlinchey, S.; Michalovich, D.; Al-Lazikani, B. ChEMBL: A Large-Scale Bioactivity Database for Drug Discovery. Nucleic Acids Res. 2011, 40 (D1), D1100–D1107.
54. Irwin, J. J.; Shoichet, B. K. ZINC- a Free Database of Commercially Available Compounds for Virtual Screening. J. Chem. Inf. Model. 2005, 45 (1), 177–182.
55. Schneidman-Duhovny, D.; Dror, O.; Inbar, Y.; Nussinov, R.; Wolfson, H. J. PharmaGist: A Webserver for Ligand-Based Pharmacophore Detection. Nucleic Acids Res. 2008, 36 (suppl_2), W223–W228.
56. Irwin, J. J.; Shoichet, B. K.; Mysinger, M. M.; Huang, N.; Colizzi, F.; Wassam, P.; Cao, Y. Automated Docking Screens: A Feasibility Study. J. Med. Chem. 2009, 52 (18), 5712–5720.
57. Labbé, C. M.; Rey, J.; Lagorce, D.; Vavruša, M.; Becot, J.; Sperandio, O.; Villoutreix, B. O.; Tufféry, P.; Miteva, M. A. MTiOpenScreen: A Web Server for Structure-Based Virtual Screening. Nucleic Acids Res. 2015, 43 (W1), W448–W454.
58. Sunseri, J.; Koes, D. R. Pharmit: Interactive Exploration of Chemical Space. Nucleic Acids Res. 2016, 44 (W1), W442–W448.
59. Koes, D. R.; Camacho, C. J. ZINCPharmer: Pharmacophore Search of the ZINC Database. Nucleic Acids Res. 2012, 40 (W1), W409–W414.
60. Verma, J.; Khedkar, V. M.; Coutinho, E. C. 3D-QSAR in Drug Design-a Review. Curr. Top. Med. Chem. 2010, 10 (1), 95–115.
61. Bordás, B.; K\Homíves, T.; Lopata, A. Ligand-Based Computer-Aided Pesticide Design. A Review of Applications of the CoMFA and CoMSIA Methodologies. Pest Manag. Sci. Former. Pestic. Sci. 2003, 59 (4), 393–400.
62. Koes, D. R. Pharmacophore Modeling: Methods and Applications. In Computer-Aided Drug Discovery; Zhang, W., Ed.; Methods in Pharmacology and Toxicology; Springer New York: New York, NY, 2016; pp 167–188.
63. Sheridan, R. P.; Kearsley, S. K. Why Do We Need so Many Chemical Similarity Search Methods? Drug Discov. Today 2002, 7 (17), 903–911.
64. Zhang, L.; Tsai, K.-C.; Du, L.; Fang, H.; Li, M.; Xu, W. How to Generate Reliable and Predictive CoMFA Models. Curr. Med. Chem. 2011, 18 (6), 923–930.
65. Roy, K.; Kar, S.; Das, R. N. Understanding the Basics of QSAR for Applications in Pharmaceutical Sciences and Risk Assessment; Academic press, 2015.
66. Tikhonova, I. G. Application of GPCR Structures for Modelling of Free Fatty Acid Receptors. In Free Fatty Acid Receptors; Springer, 2016; pp 57–77.
67. Sun, Q.; Hirasawa, A.; Hara, T.; Kimura, I.; Adachi, T.; Awaji, T.; Ishiguro, M.; Suzuki, T.; Miyata, N.; Tsujimoto, G. Structure-Activity Relationships of GPR120 Agonists Based on a Docking Simulation. Mol. Pharmacol. 2010, 78 (5), 804–810.
68. Suzuki, T.; Igari, S.; Hirasawa, A.; Hata, M.; Ishiguro, M.; Fujieda, H.; Itoh, Y.; Hirano, T.; Nakagawa, H.; Ogura, M. Identification of G Protein-Coupled Receptor 120-Selective Agonists Derived from PPARγ Agonists. J. Med. Chem. 2008, 51 (23), 7640–7644.
69. Watson, S.-J.; Brown, A. J.; Holliday, N. D. Differential Signaling by Splice Variants of the Human Free Fatty Acid Receptor GPR120. Mol. Pharmacol. 2012, 81 (5), 631–642.
70. Hudson, B. D.; Shimpukade, B.; Milligan, G.; Ulven, T. The Molecular Basis of Ligand Interaction at Free Fatty Acid Receptor 4 (FFA4/GPR120). J. Biol. Chem. 2014, 289 (29), 20345–20358.
71. Hara, T.; Hirasawa, A.; Sun, Q.; Sadakane, K.; Itsubo, C.; Iga, T.; Adachi, T.; Koshimizu, T.; Hashimoto, T.; Asakawa, Y. Novel Selective Ligands for Free Fatty Acid Receptors GPR120 and GPR40. Naunyn. Schmiedebergs Arch. Pharmacol. 2009, 380 (3), 247–255.
72. Takeuchi, M.; Hirasawa, A.; Hara, T.; Kimura, I.; Hirano, T.; Suzuki, T.; Miyata, N.; Awaji, T.; Ishiguro, M.; Tsujimoto, G. FFA1-Selective Agonistic Activity Based on Docking Simulation Using FFA1 and GPR120 Homology Models. Br. J. Pharmacol. 2013, 168 (7), 1570–1583.
73. Rasmussen, S. G.; Choi, H.-J.; Fung, J. J.; Pardon, E.; Casarosa, P.; Chae, P. S.; DeVree, B. T.; Rosenbaum, D. M.; Thian, F. S.; Kobilka, T. S. Structure of a Nanobody-Stabilized Active State of the β 2 Adrenoceptor. Nature 2011, 469 (7329), 175.
2. Usfar, A. A.; Lebenthal, E.; Achadi, E.; Hadi, H. Obesity as a Poverty-Related Emerging Nutrition Problems: The Case of Indonesia. Obes. Rev. 2010, 11 (12), 924–928.
3. Al-Goblan, A. S.; Al-Alfi, M. A.; Khan, M. Z. Mechanism Linking Diabetes Mellitus and Obesity. Diabetes Metab. Syndr. Obes. Targets Ther. 2014, 7, 587–591. https://doi.org/10.2147/DMSO.S67400.
4. Dandona, P.; Aljada, A.; Chaudhuri, A.; Mohanty, P.; Garg, R. Metabolic Syndrome: A Comprehensive Perspective Based on Interactions between Obesity, Diabetes, and Inflammation. Circulation 2005, 111 (11), 1448–1454.
5. Golay, A.; Ybarra, J. Link between Obesity and Type 2 Diabetes. Best Pract. Res. Clin. Endocrinol. Metab. 2005, 19 (4), 649–663.
6. Roglic, G. WHO Global Report on Diabetes: A Summary. Int. J. Noncommunicable Dis. 2016, 1 (1), 3.
7. Czech, M. P. Insulin Action and Resistance in Obesity and Type 2 Diabetes. Nat. Med. 2017, 23 (7), 804–814.
8. Guariguata, L.; Whiting, D. R.; Hambleton, I.; Beagley, J.; Linnenkamp, U.; Shaw, J. E. Global Estimates of Diabetes Prevalence for 2013 and Projections for 2035. Diabetes Res. Clin. Pract. 2014, 103 (2), 137–149.
9. Soewondo, P.; Soegondo, S.; Suastika, K.; Pranoto, A.; Soeatmadji, D. W.; Tjokroprawiro, A. The DiabCare Asia 2008 Study–Outcomes on Control and Complications of Type 2 Diabetic Patients in Indonesia. Med. J. Indones. 2010, 19 (4), 235–44.
10. Azimova, K.; San Juan, Z.; Mukherjee, D. Cardiovascular Safety Profile of Currently Available Diabetic Drugs. Ochsner J. 2014, 14 (4), 616–632.
11. Scheen, A. Thiazolidinediones and Liver Toxicity. Diabetes Metab. 2001, 27 (3), 305–13.
12. Bouchoucha, M.; Uzzan, B.; Cohen, R. Metformin and Digestive Disorders. Diabetes Metab. 2011, 37 (2), 90–96.
13. Richter, B.; Bandeira-Echtler, E.; Bergerhoff, K.; Lerch, C. Dipeptidyl Peptidase-4 (DPP-4) Inhibitors for Type 2 Diabetes Mellitus. Cochrane Database Syst. Rev. 2008, No. 2.
14. Rosenstock, J.; Ferrannini, E. Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, and Preventable Safety Concern with SGLT2 Inhibitors. Diabetes Care 2015, 38 (9), 1638–1642.
15. Association, A. D. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2013, 36 (Supplement 1), S67–S74.
16. Stein, S. A.; Lamos, E. M.; Davis, S. N. A Review of the Efficacy and Safety of Oral Antidiabetic Drugs. Expert Opin. Drug Saf. 2013, 12 (2), 153–175.
17. Goodarzi, M. O.; Bryer-Ash, M. Metformin Revisited: Re-Evaluation of Its Properties and Role in the Pharmacopoeia of Modern Antidiabetic Agents. Diabetes Obes. Metab. 2005, 7 (6), 654–665.
18. Amini, F. G.; Rafieian-Kopaei, M.; Nematbakhsh, M.; Baradaran, A.; Nasri, H. Ameliorative Effects of Metformin on Renal Histologic and Biochemical Alterations of Gentamicin-Induced Renal Toxicity in Wistar Rats. J. Res. Med. Sci. Off. J. Isfahan Univ. Med. Sci. 2012, 17 (7), 621.
19. Liu, K. W.; Dai, L. K.; Jean, W. Metformin-Related Vitamin B12 Deficiency. Age Ageing 2006, 35 (2), 200–201.
20. Natali, A.; Ferrannini, E. Effects of Metformin and Thiazolidinediones on Suppression of Hepatic Glucose Production and Stimulation of Glucose Uptake in Type 2 Diabetes: A Systematic Review. Diabetologia 2006, 49 (3), 434–441.
21. Lago, R. M.; Singh, P. P.; Nesto, R. W. Congestive Heart Failure and Cardiovascular Death in Patients with Prediabetes and Type 2 Diabetes given Thiazolidinediones: A Meta-Analysis of Randomised Clinical Trials. The Lancet 2007, 370 (9593), 1129–1136.
22. Karagiannis, T.; Paschos, P.; Paletas, K.; Matthews, D. R.; Tsapas, A. Dipeptidyl Peptidase-4 Inhibitors for Treatment of Type 2 Diabetes Mellitus in the Clinical Setting: Systematic Review and Meta-Analysis. Bmj 2012, 344, e1369.
23. Hauser, A. S.; Attwood, M. M.; Rask-Andersen, M.; Schiöth, H. B.; Gloriam, D. E. Trends in GPCR Drug Discovery: New Agents, Targets and Indications. Nat. Rev. Drug Discov. 2017, 16 (12), 829.
24. Andrews, S. P.; Brown, G. A.; Christopher, J. A. Structure-Based and Fragment-Based GPCR Drug Discovery. ChemMedChem 2014, 9 (2), 256–275.
25. Liu, H.-D.; Wang, W.; Xu, Z.; Liu, C.; He, D.; Du, L.-P.; Li, M.-Y.; Yu, X.; Sun, J. FFA4 Receptor (GPR120): A Hot Target for the Development of Anti-Diabetic Therapies. Eur. J. Pharmacol. 2015, 763, 160–168.
26. Brown, A. J.; Jupe, S.; Briscoe, C. P. A Family of Fatty Acid Binding Receptors. DNA Cell Biol. 2005, 24 (1), 54–61.
27. Hara, T.; Kashihara, D.; Ichimura, A.; Kimura, I.; Tsujimoto, G.; Hirasawa, A. Role of Free Fatty Acid Receptors in the Regulation of Energy Metabolism. Biochim. Biophys. Acta BBA-Mol. Cell Biol. Lipids 2014, 1841 (9), 1292–1300.
28. Fredriksson, R.; Höglund, P. J.; Gloriam, D. E.; Lagerström, M. C.; Schiöth, H. B. Seven Evolutionarily Conserved Human Rhodopsin G Protein-Coupled Receptors Lacking Close Relatives. FEBS Lett. 2003, 554 (3), 381–388.
29. Ichimura, A.; Hirasawa, A.; Hara, T.; Tsujimoto, G. Free Fatty Acid Receptors Act as Nutrient Sensors to Regulate Energy Homeostasis. Prostaglandins Other Lipid Mediat. 2009, 89 (3–4), 82–88.
30. Miyamoto, J.; Hasegawa, S.; Kasubuchi, M.; Ichimura, A.; Nakajima, A.; Kimura, I. Nutritional Signaling via Free Fatty Acid Receptors. Int. J. Mol. Sci. 2016, 17 (4), 450.
31. Olefsky, J. M. Omega 3 Fatty Acids and GPR120. Cell Metab. 2012, 15 (5), 564–565.
32. Talukdar, S.; Bae, E. J.; Imamura, T.; Morinaga, H.; Fan, W.; Li, P.; Lu, W. J.; Watkins, S. M.; Olefsky, J. M. GPR120 Is an Omega-3 Fatty Acid Receptor Mediating Potent Anti-Inflammatory and Insulin-Sensitizing Effects. Cell 2010, 142 (5), 687–698.
33. Li, A.; Li, Y.; Du, L. Biological Characteristics and Agonists of GPR120 (FFAR4) Receptor: The Present Status of Research. Future Med. Chem. 2015, 7 (11), 1457–1468.
34. Briscoe, C. P.; Peat, A. J.; McKeown, S. C.; Corbett, D. F.; Goetz, A. S.; Littleton, T. R.; McCoy, D. C.; Kenakin, T. P.; Andrews, J. L.; Ammala, C. Pharmacological Regulation of Insulin Secretion in MIN6 Cells through the Fatty Acid Receptor GPR40: Identification of Agonist and Antagonist Small Molecules. Br. J. Pharmacol. 2006, 148 (5), 619–628.
35. Shimpukade, B.; Hudson, B. D.; Hovgaard, C. K.; Milligan, G.; Ulven, T. Discovery of a Potent and Selective GPR120 Agonist. J. Med. Chem. 2012, 55 (9), 4511–4515.
36. Halder, S.; Kumar, S.; Sharma, R. The Therapeutic Potential of GPR120: A Patent Review. Expert Opin. Ther. Pat. 2013, 23 (12), 1581–1590.
37. Zhang, D.; Leung, P. S. Potential Roles of GPR120 and Its Agonists in the Management of Diabetes. Drug Des. Devel. Ther. 2014, 8, 1013.
38. Hudson, B. D.; Shimpukade, B.; Mackenzie, A. E.; Butcher, A. J.; Pediani, J. D.; Christiansen, E.; Heathcote, H.; Tobin, A. B.; Ulven, T.; Milligan, G. The Pharmacology of TUG-891, a Potent and Selective Agonist of the Free Fatty Acid Receptor 4 (FFA4/GPR120), Demonstrates Both Potential Opportunity and Possible Challenges to Therapeutic Agonism. Mol. Pharmacol. 2013, 84 (5), 710–725.
39. Schilperoort, M.; van Dam, A. D.; Hoeke, G.; Shabalina, I. G.; Okolo, A.; Hanyaloglu, A. C.; Dib, L. H.; Mol, I. M.; Caengprasath, N.; Chan, Y.-W. The GPR120 Agonist TUG-891 Promotes Metabolic Health by Stimulating Mitochondrial Respiration in Brown Fat. EMBO Mol. Med. 2018, 10 (3).
40. Sparks, S. M.; Chen, G.; Collins, J. L.; Danger, D.; Dock, S. T.; Jayawickreme, C.; Jenkinson, S.; Laudeman, C.; Leesnitzer, M. A.; Liang, X. Identification of Diarylsulfonamides as Agonists of the Free Fatty Acid Receptor 4 (FFA4/GPR120). Bioorg. Med. Chem. Lett. 2014, 24 (14), 3100–3103.
41. Bruno, A.; Aiello, F.; Costantino, G.; Radi, M. Homology Modeling, Validation and Dynamics of the G Protein-Coupled Estrogen Receptor 1 (GPER-1). Mol. Inform. 2016, 35 (8–9), 333–339.
42. França, T. C. C. Homology Modeling: An Important Tool for the Drug Discovery. J. Biomol. Struct. Dyn. 2015, 33 (8), 1780–1793.
43. Nero, T. L.; Parker, M. W.; Morton, C. J. Protein Structure and Computational Drug Discovery. Biochem. Soc. Trans. 2018, 46 (5), 1367–1379. https://doi.org/10.1042/BST20180202.
44. Macalino, S. J. Y.; Gosu, V.; Hong, S.; Choi, S. Role of Computer-Aided Drug Design in Modern Drug Discovery. Arch. Pharm. Res. 2015, 38 (9), 1686–1701.
45. Davis, A. M.; Teague, S. J.; Kleywegt, G. J. Application and Limitations of X-Ray Crystallographic Data in Structure-Based Ligand and Drug Design. Angew. Chem. Int. Ed. 2003, 42 (24), 2718–2736.
46. Webb, B.; Sali, A. Protein Structure Modeling with MODELLER. In Functional Genomics; Springer, 2017; pp 39–54.
47. Schwede, T.; Kopp, J.; Guex, N.; Peitsch, M. C. SWISS-MODEL: An Automated Protein Homology-Modeling Server. Nucleic Acids Res. 2003, 31 (13), 3381–3385.
48. Kelley, L. A.; Mezulis, S.; Yates, C. M.; Wass, M. N.; Sternberg, M. J. E. The Phyre2 Web Portal for Protein Modeling, Prediction and Analysis. Nat. Protoc. 2015, 10 (6), 845–858. https://doi.org/10.1038/nprot.2015.053.
49. Yang, J.; Zhang, Y. I-TASSER Server: New Development for Protein Structure and Function Predictions. Nucleic Acids Res. 2015, 43 (W1), W174–W181.
50. Lybrand, T. P. Ligand—Protein Docking and Rational Drug Design. Curr. Opin. Struct. Biol. 1995, 5 (2), 224–228.
51. Khan, S. U.; Ahemad, N.; Chuah, L.-H.; Naidu, R.; Htar, T. T. Sequential Ligand-and Structure-Based Virtual Screening Approach for the Identification of Potential G Protein-Coupled Estrogen Receptor-1 (GPER-1) Modulators. RSC Adv. 2019, 9 (5), 2525–2538.
52. Jacob, R. B.; Andersen, T.; McDougal, O. M. Accessible High-Throughput Virtual Screening Molecular Docking Software for Students and Educators. PLoS Comput. Biol. 2012, 8 (5), e1002499.
53. Gaulton, A.; Bellis, L. J.; Bento, A. P.; Chambers, J.; Davies, M.; Hersey, A.; Light, Y.; McGlinchey, S.; Michalovich, D.; Al-Lazikani, B. ChEMBL: A Large-Scale Bioactivity Database for Drug Discovery. Nucleic Acids Res. 2011, 40 (D1), D1100–D1107.
54. Irwin, J. J.; Shoichet, B. K. ZINC- a Free Database of Commercially Available Compounds for Virtual Screening. J. Chem. Inf. Model. 2005, 45 (1), 177–182.
55. Schneidman-Duhovny, D.; Dror, O.; Inbar, Y.; Nussinov, R.; Wolfson, H. J. PharmaGist: A Webserver for Ligand-Based Pharmacophore Detection. Nucleic Acids Res. 2008, 36 (suppl_2), W223–W228.
56. Irwin, J. J.; Shoichet, B. K.; Mysinger, M. M.; Huang, N.; Colizzi, F.; Wassam, P.; Cao, Y. Automated Docking Screens: A Feasibility Study. J. Med. Chem. 2009, 52 (18), 5712–5720.
57. Labbé, C. M.; Rey, J.; Lagorce, D.; Vavruša, M.; Becot, J.; Sperandio, O.; Villoutreix, B. O.; Tufféry, P.; Miteva, M. A. MTiOpenScreen: A Web Server for Structure-Based Virtual Screening. Nucleic Acids Res. 2015, 43 (W1), W448–W454.
58. Sunseri, J.; Koes, D. R. Pharmit: Interactive Exploration of Chemical Space. Nucleic Acids Res. 2016, 44 (W1), W442–W448.
59. Koes, D. R.; Camacho, C. J. ZINCPharmer: Pharmacophore Search of the ZINC Database. Nucleic Acids Res. 2012, 40 (W1), W409–W414.
60. Verma, J.; Khedkar, V. M.; Coutinho, E. C. 3D-QSAR in Drug Design-a Review. Curr. Top. Med. Chem. 2010, 10 (1), 95–115.
61. Bordás, B.; K\Homíves, T.; Lopata, A. Ligand-Based Computer-Aided Pesticide Design. A Review of Applications of the CoMFA and CoMSIA Methodologies. Pest Manag. Sci. Former. Pestic. Sci. 2003, 59 (4), 393–400.
62. Koes, D. R. Pharmacophore Modeling: Methods and Applications. In Computer-Aided Drug Discovery; Zhang, W., Ed.; Methods in Pharmacology and Toxicology; Springer New York: New York, NY, 2016; pp 167–188.
63. Sheridan, R. P.; Kearsley, S. K. Why Do We Need so Many Chemical Similarity Search Methods? Drug Discov. Today 2002, 7 (17), 903–911.
64. Zhang, L.; Tsai, K.-C.; Du, L.; Fang, H.; Li, M.; Xu, W. How to Generate Reliable and Predictive CoMFA Models. Curr. Med. Chem. 2011, 18 (6), 923–930.
65. Roy, K.; Kar, S.; Das, R. N. Understanding the Basics of QSAR for Applications in Pharmaceutical Sciences and Risk Assessment; Academic press, 2015.
66. Tikhonova, I. G. Application of GPCR Structures for Modelling of Free Fatty Acid Receptors. In Free Fatty Acid Receptors; Springer, 2016; pp 57–77.
67. Sun, Q.; Hirasawa, A.; Hara, T.; Kimura, I.; Adachi, T.; Awaji, T.; Ishiguro, M.; Suzuki, T.; Miyata, N.; Tsujimoto, G. Structure-Activity Relationships of GPR120 Agonists Based on a Docking Simulation. Mol. Pharmacol. 2010, 78 (5), 804–810.
68. Suzuki, T.; Igari, S.; Hirasawa, A.; Hata, M.; Ishiguro, M.; Fujieda, H.; Itoh, Y.; Hirano, T.; Nakagawa, H.; Ogura, M. Identification of G Protein-Coupled Receptor 120-Selective Agonists Derived from PPARγ Agonists. J. Med. Chem. 2008, 51 (23), 7640–7644.
69. Watson, S.-J.; Brown, A. J.; Holliday, N. D. Differential Signaling by Splice Variants of the Human Free Fatty Acid Receptor GPR120. Mol. Pharmacol. 2012, 81 (5), 631–642.
70. Hudson, B. D.; Shimpukade, B.; Milligan, G.; Ulven, T. The Molecular Basis of Ligand Interaction at Free Fatty Acid Receptor 4 (FFA4/GPR120). J. Biol. Chem. 2014, 289 (29), 20345–20358.
71. Hara, T.; Hirasawa, A.; Sun, Q.; Sadakane, K.; Itsubo, C.; Iga, T.; Adachi, T.; Koshimizu, T.; Hashimoto, T.; Asakawa, Y. Novel Selective Ligands for Free Fatty Acid Receptors GPR120 and GPR40. Naunyn. Schmiedebergs Arch. Pharmacol. 2009, 380 (3), 247–255.
72. Takeuchi, M.; Hirasawa, A.; Hara, T.; Kimura, I.; Hirano, T.; Suzuki, T.; Miyata, N.; Awaji, T.; Ishiguro, M.; Tsujimoto, G. FFA1-Selective Agonistic Activity Based on Docking Simulation Using FFA1 and GPR120 Homology Models. Br. J. Pharmacol. 2013, 168 (7), 1570–1583.
73. Rasmussen, S. G.; Choi, H.-J.; Fung, J. J.; Pardon, E.; Casarosa, P.; Chae, P. S.; DeVree, B. T.; Rosenbaum, D. M.; Thian, F. S.; Kobilka, T. S. Structure of a Nanobody-Stabilized Active State of the β 2 Adrenoceptor. Nature 2011, 469 (7329), 175.
Published
2020-06-25
How to Cite
SAUDALE, F., TOKAN, M., LEO, S., & ATI, S. (2020). FFAR4/GPR120 SEBAGAI TARGET DESAIN DAN PENGEMBANGAN OBAT DIABETES MELITUS TIPE 2 IN SILICO: SUATU TINJAUAN DAN PERSPEKTIF. Chemistry Notes, 2(1), 12-35. https://doi.org/10.35508/cn.v2i1.2338
Section
Articles
In order to publish in Chemistry Notes, authors are required to agree to the copyright permission stating that the authors give the publisher the right to reproduce, display or distribute the accepted manuscript. In this agreement the authors also automatically declare that the submitted manuscript is exempted from plagiarism issue and conflict of interest among the authors.
