Small molecule inhibitors of human adipocyte fatty acid binding protein (FABP4)

Medicinal Chemistry

Volumn 10, Issue 4, 2014, Pages 339-347

  Zhang, Mingming ^a   Zhu, Weiliang ^b   Li, Yingxia ^a  

^a FUDAN UNIVERSITY   (China)

^b SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

Author keywords

FABP4; Fatty acid binding protein 4; Inhibitor; Receptor; Small molecule; Type 2 diabetes

Indexed keywords

BIPHENYL DERIVATIVE; FATTY ACID BINDING PROTEIN 4; FATTY ACID DERIVATIVE; PYRIMIDINE DERIVATIVE; PYRROLE DERIVATIVE; FABP4 PROTEIN, HUMAN; FATTY ACID BINDING PROTEIN; MOLECULAR LIBRARY;

ADIPOCYTE; ARTICLE; ATHEROSCLEROSIS; CELL MEMBRANE; FATTY ACID METABOLISM; HEART; MACROPHAGE; METABOLIC SYNDROME X; METABOLISM; MITOCHONDRION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PRIORITY JOURNAL; SKELETAL MUSCLE; STRUCTURE ACTIVITY RELATION; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; GENETICS; HUMAN; MOLECULAR LIBRARY; PHARMACOLOGY; SYNTHESIS;

ADIPOCYTES; FATTY ACID-BINDING PROTEINS; HUMANS; MODELS, MOLECULAR; SMALL MOLECULE LIBRARIES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84899822367     PISSN: 15734064     EISSN: 18756638     Source Type: Journal    
DOI: 10.2174/15734064113096660045     Document Type: Article

References (37)

1. Storch, J.; Corsico, B. The emerging functions and mechanisms of mammalian fatty acid-binding proteins. Annu. Rev. Nutr., 2008, 28, 73-95.
2. Chmurzyńska, A. The multigene family of fatty acid-binding proteins (FABPs): function, structure and polymorphism. J. Appl. Genet., 2006, 47, 39-48.
3. Haunerland, N.H.; Spener, F. Fatty acid-binding proteins-insights from genetic manipulations. Prog. Lipid Res., 2004, 43, 328-49.
4. Furuhashi, M.; Fucho, R.; Gorgun, C.Z.; Tuncman, G.; Cao, H.; Hotamisligil, G.S. Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice. J. Clin. Invest., 2008, 118, 2640-50.
5. Hotamisligil, G.S.; Johnson, R.S.; Distel, R.J.; Ellis, R.; Papaioannou, V.E.; Spiegelman, B.M. Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science, 1996, 274, 1377-79.
6. Uysal, K.T.; Scheja, L.; Wiesbrock, S.M.; Bonner-Weir, S.; Hotamisligil, G.S. Improved glucose and lipid metabolism in genetically obese mice lacking aP2. Endocrinology, 2000, 141, 3388-96.
7. Shen, W.J.; Sridhar, K.; Bernlohr, D.A.; Kraemer, F.B. Interaction of rat hormone-sensitive lipase with adipocyte lipid-binding protein. Proc. Natl. Acad. Sci. U.S.A., 1999, 96, 5528-32.
8. Scheja, L.; Makowski, L.; Uysal, K.T.; Wiesbrock, S.M.; Shimshek, D.R.; Meyers, D.S.; Morgan, M.; Parker, R.A.; Hotamisligil, G.S. Altered insulin secretion associated with reduced lipolytic efficiency in aP2-/- mice. Diabetes, 1999, 48, 1987-94.
9. Coe, N.R.; Simpson, M.A.; Bernlohr, D.A. Targeted disruption of the adipocyte lipid-binding protein (aP2 protein) gene impairs fat cell lipolysis and increases cellular fatty acid levels. J. Lipid Res., 1999, 40, 967-72.
10. Makowski, L.; Boord, J.B.; Maeda, K.; Babaev, V.R.; Uysal, K.T.; Morgan, M.A.; Parker, R.A.; Suttles, J.; Fazio, S.; Hotamisligil, G.S.; Linton, M.F. Lack of macrophage fatty-acid -binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis. Nat. Med., 2001, 7, 699-705.
11. Makowski, L.; Brittingham, K.C.; Reynolds, J.M.; Suttles, J.; Hotamisligil, G.S. The fatty acid-binding protein, aP2, coordinates macrophage cholesterol trafficking and inflammatory activity. Macrophage expression of aP2 impacts peroxisome proliferatoractivated receptor γ and IκB kinase activities. J. Biol. Chem., 2005, 280, 12888-95.
12. Beniyama, Y.; Matsuno, K.; Miyachi, H. Structure-guided design, synthesis and in vitro evaluation of a series of pyrazole-based fatty acid binding protein (FABP) 3 ligands. Bioorg. Med. Chem. Lett., 2013, 23, 1662-6.
13. Jenkins-Kruchten, A.E.; Bennaars-Eiden, A.; Ross, J.R.; Shen, W.J.; Kraemer, F.B.; Bernlohr, D.A. Fatty acid-bindingproteinhormone-sensitive lipase interaction. Fatty acid dependence on binding. J. Biol. Chem., 2003, 278, 47636-43.
14. Smith, A.J.; Thompson, B.R.; Sanders, M.A.; Bernlohr, D.A. Interaction of the adipocyte fatty acid-binding protein with the hormone-sensitive lipase: regulation by fatty acids and phosphorylation. J. Biol. Chem., 2007, 282, 32424-32.
15. Thompson, B.R.; Muzurkiewicz-Munoz, A.M.; Suttles, J.; Carter-Su, C.; Bernlohr, D.A. Interaction of adipocyte fatty acid-binding protein (AFABP) and JAK2: AFABP/aP2 as a regulator of JAK2 signaling. J. Biol. Chem., 2009, 284, 13473-80.
16. Adida, A.; Spener, F. Adipocyte-type fatty acid-binding protein as intercompartmental shuttle for peroxisome proliferator activated receptor gamma agonists in cultured cell. Biochim. Biophys. Acta., 2006, 1761, 172-81.
17. Ayers, S.D.; Nedrow, K.L.; Gillilan, R.E.; Noy, N. Continuous nucleocytoplasmic shuttling underlies transcriptional activation of PPARgamma by FABP4. Biochemistry, 2007, 46, 6744-52.
18. Chmurzyńska, A. The multigene family of fatty acid-binding proteins (FABPs): function, structure and polymorphism. J. Appl. Genet., 2006, 47, 39-48.
19. Xu, Z.; Bernlohr, D.A.; Banaszak, L.J. The adipocyte lipid-binding protein at 1.6-A resolution. J. Biol. Chem., 1993, 268, 7874-8.
20. Storch, J.; McDermott, L. Structural and functional analysis of fatty acid-binding proteins. J. Lipid Res., 2009, (50 Suppl.), S126-31.
21. Lehmann, F.; Haile, S.; Axen, E.; Medina, C.; Uppenberg, J.; Svensson, S.; Lundbäck, T.; Rondahl, L.; Barf, T. Discovery of inhibitors of human adipocyte fatty acid-binding protein, a potential type 2 diabetes target. Bioorg. Med. Chem. Lett., 2004, 14, 4445-8.
22. Barf, T.; Lehmann, F.; Hammer, K.; Haile, S.; Axen, E.; Medina, C.; Uppenberg, J.; Svensson, S.; Rondahl, L.; Lundbäck, T.N-Benzyl-indolo carboxylic acids: Design and synthesis of potent and selective adipocyte fatty-acid binding protein (A-FABP) inhibitors. Bioorg. Med. Chem. Lett., 2009, 19, 1745-8.
23. Xu, Q.; Huang, L.; Liu, J.; Ma, L.; Chen, T.; Chen, J.; Peng, F.; Cao, D.; Yang, Z.; Qiu, N.; Qiu, J.; Wang, G.; Liang, X.; Peng, A.; Xiang, M.; Wei, Y.; Chen, L. Design, synthesis and biological evaluation of thiazole- and indole-based derivatives for the treatment of type II diabetes. Eur. J. Med. Chem., 2012, 52, 70-81.
24. Sulsky, R.; Magnin, D.R.; Huang, Y.; Simpkins, L.; Taunk, P.; Patel, M.; Zhu, Y.; Stouch, T.R.; Bassolino-Klimas, D.; Parker, R.; Harrity, T.; Stoffel, R.; Taylor, D.S.; Lavoie, T.B.; Kish, K.; Jacobson, B.L.; Sheriff, S.; Adam, L.P.; Ewing, W.R.; Robl, J.A. Potent and selective biphenyl azole inhibitors of adipocyte fatty acid binding protein (aFABP). Bioorg. Med. Chem. Lett., 2007, 17, 3511-5.
25. Furuhashi, M.; Tuncman, G.; Görgün, C.Z.; Makowski, L.;Atsumi, G.; Vaillancourt, E.; Kono, K.;Babaev, V.R.; Fazio, S.; Linton, M.F.; Sulsky, R.; Robl, J.A.; Parker, R.A.; Hotamisligil, G.S. Treatment of diabetes and atherosclerosis by inhibiting fatty-acidbinding protein aP2. Nature, 2007, 447, 959-65.
26. Hirosumi, J.; Tuncman, G.; Chang, L.; Görgün, C.Z.; Uysal, K.T.; Maeda, K.; Karin, M.; Hotamisligil, G.S.A centralrole for JNK in obesity and insulin resistance. Nature, 2002, 420, 333-6.
27. Tuncman, G.; Hirosumi, J.; Solinas, G.; Chang, L.; Karin, M.; Hotamisligil, G.S. Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance. Proc. Natl. Acad. Sci. U.S.A., 2006, 103, 10741-6.
28. Liu, X.; Huang, X.; Lin, W.; Wang, D.; Diao, Y.; Li, H.; Hui, X.; Wang, Y.; Xu, A.; Wu, D.; Ke, D. New aromatic substituted pyrazoles as selective inhibitors of human adipocyte fatty acid-binding protein. Bioorg. Med. Chem. Lett., 2011, 21, 2949-52.
29. 14C]BMS-309403, a radioligand for adipocyte fatty acid binding protein. Chem. Pharm. Bull., 2012, 60, 164-68.
30. Escoté, X.; Megia, A.; López-Dupla, M.; Miranda, M.; Veloso, S.; Alba, V.; Domingo, P.; Pardo, P.; Viladés, C.; Peraire, J.; Giralt, M.; Richart, C.; Vendrell, J.; Vidal, F. HIV-1 Lipodystrophy Study Group. A study of fatty acid binding protein 4 in HIV-1 infection and in combination antiretroviral therapy-related metabolic disturbances and lipodystrophy. HIV Med., 2011, 12, 428-37.
31. Hertzel, A.V.; Hellberg, K.; Reynolds, J.M.; Kruse, A.C.; Juhlmann, B.E.; Smith, A.J.; Sanders, M.A.; Ohlendorf, D.H.; Suttles, J.; Bernlohr, D.A. Identification and characterization of a small molecule inhibitor of Fatty Acid binding proteins. J. Med. Chem., 2009, 52, 6024-31.
32. Ringom, R.; Axen, E.; Uppenberg, J.; Lundbäck, T.; Rondahl, L.; Barf, T. Substituted benzylamino-6-(trifluoromethyl)pyrimidin-4(1H)-ones: a novel class of selective human A-FABP inhibitors. Bioorg. Med. Chem. Lett., 2004, 14, 4449-52.
33. Maeda, K.; Cao, H.; Kono, K.; Gorgun, C.Z.; Furuhashi, M.; Uysal, K.T.; Cao, Q.; Atsumi, G.; Malone, H.; Krishnan, B.; Minokoshi, Y.; Kahn, B.B.; Parker, R.A.; Hotamisligil, G.S. Adipocyte/ macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes. Cell Metab., 2005, 1, 107-19.
34. Shipps, G.W. Jr.; Cheng, C.C.; Huang, X.; Achab, A.A.; Orth, P.; Voigt, J.H.; Soucy, K.A. Inhibitors of fatty acid binding protein (FABP). WO 2010/056631, May 20, 2010.
35. Lan, H.; Cheng, C.C.; Kowalski, T.J.; Pang, L.; Shan, L.; Chuang, C.C.; Jackson, J.; Rojas-Triana, A.; Bober, L.; Liu, L.; Voigt, J.; Orth, P.; Yang, X.; Shipps, G.W. Jr.; Hedrick, J.A. Small-molecule inhibitors of FABP4/5 ameliorate dyslipidemia but not insulin resistance in mice with diet-induced obesity. J. Lipid. Res., 2011, 52, 646-56.
36. Cai, H.; Yan, G.; Zhang, X.; Gorbenko, O.; Wang, H.; Zhu, W. Discovery of highly selective inhibitors of human fatty acid binding protein 4 (FABP4) by virtual screening. Bioorg. Med. Chem. Lett., 2010, 20, 3675-9.
37. Cheng, C.C.; Shipps, G.W. Jr.; Huang, X.; Shao, N.; Rao, A.; Palani, A.; Voigt, J.H.; Herr, R.J.; Rossiter, L.M.; Zeng, Q.; Sun, X. Inhibitors of fatty acid binding protein. U.S. Patent 2012/0122837, May 17, 2012.