Therapeutic potential for thyroid hormone receptor-β selective agonists for treating obesity, hyperlipidemia and diabetes

Current Vascular Pharmacology

Volumn 5, Issue 2, 2007, Pages 141-154

  Grover, Gary J ^a,b   Mellström, Karin ^a,b   Malm, Johan ^a,b  

^a Eurofins Medinet Inc   (United States)

^b Karo Bio   (Sweden)

Author keywords

Cholesterol; KB 141; Obesity; Thyroid hormone agonists; Thyroid hormone receptor P

Indexed keywords

CGS 23425; GC 1; GCS 23425; KB 141; LOW DENSITY LIPOPROTEIN; THYROID HORMONE; THYROID HORMONE RECEPTOR BETA; THYROMIMETIC AGENT; THYROTROPIN; UNCLASSIFIED DRUG; ANTIDIABETIC AGENT; ANTILIPEMIC AGENT; ANTIOBESITY AGENT; DIPHENYL ETHER DERIVATIVE; PHENYLACETIC ACID DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; BINDING AFFINITY; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG DOSE COMPARISON; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG UPTAKE; HUMAN; HYPERLIPIDEMIA; METABOLIC RATE; NONHUMAN; OBESITY; REVIEW; STRUCTURE ACTIVITY RELATION; THYROID HORMONE METABOLISM; THYROTROPIN RELEASE; ANIMAL; DIABETES MELLITUS; DRUG POTENTIATION; GENETICS; MOUSE; MOUSE MUTANT; PATHOPHYSIOLOGY; PHYSIOLOGY; PRIMATE; RAT; THYROID DISEASE;

ANIMALS; ANTI-OBESITY AGENTS; ANTILIPEMIC AGENTS; DIABETES MELLITUS; HUMANS; HYPERLIPIDEMIAS; HYPOGLYCEMIC AGENTS; MICE; MICE, KNOCKOUT; OBESITY; PHENYL ETHERS; PHENYLACETATES; PRIMATES; RATS; THYROID DISEASES; THYROID HORMONE RECEPTORS BETA; THYROID HORMONES;

EID: 34247895631     PISSN: 15701611     EISSN: None     Source Type: Journal    
DOI: 10.2174/157016107780368271     Document Type: Review

References (73)

1. Grundy SM. Metabolic complications of obesity. Endocrine 2000; 13: 155-65.
2. Devasthale PS, Chen Y, Jeon F, Qwu C, Shao W, Wang H, et al. Design and synthesis of BMS-298585 (Muraglitizar), a novel dual peroxisome proliferators-activated receptor α/β duel agonist with efficacious glucose and lipid-lowering activities. J Med Chem 2005; 48: 2248-50.
3. Kral JG. Morbidity of severe obesity. Surg Clin North Am 2001; 81: 1039-10.
4. Weigle DS. Pharmacological therapy of obesity: past, present, and future. J Clin Endocrinol Metab 2003; 88: 2462-69.
5. Simpkins S. Dintrophenol and desiccated thyroid in the treatment of obesity. JAMA 1937; 108: 2110-19.
6. Grover GJ, Malm J. Thyroid hormone modulators: A strategy for treating metabolic syndrome. Drug Discovery Today: Therapeutic Strategies. 2005; 2: 137-42.
7. Abenhaim L, Moride Y, Brenot F, Rich J, Kurz X, Higenbottom T, et al. Appetite-suppressant drugs and the risk of primary pulmonary hypertension. N Engl J Med 1996; 335: 609-16.
8. Schwartz MW, Woods SC, Porte Jr. K, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature 2000; 404: 661-71.
9. Wadden TA, Berkowitz RI, Womble LG, Sarwer DB, Sarwer DB, Arnol ME, et al. Effects of sibutramine plus orlistat in obese women following 1 year of treatment by sibutramine alone: a placebo-controlled trial. Obes Res 2000; 8: 431-7.
10. Yen PM. Physiological and Molecular Basis of Thyroid Hormone Action. Phys Rev 2001; 81: 1097-142.
11. Ribeiro RC, Kushner PJ, Baxter JD. The nuclear hormone receptor gene superfamily. Ann Rev Med 1995; 46: 443-53.
12. Schwartz HL, Strait KA, Ling NC, Oppenheimer JH. Quantitation of rat tissue thyroid hormone binding receptor isoforms by immunoprecipitation of nuclear triiodothyronine binding capacity. J Bjol Chem 1992; 267: 11794-99.
13. Braverman LE, Utiger RD. Introduction to hypothyroidism. In: The thyroid: a fundamental and clinical text. New York, Lippincot-Raven, 1996; 736-37.
14. Lanni A, Moreno M, Lombardi A, de Lange P, Goglia F. Control of energy metabolism by iodothyronines. J Endocrinol Invest 2001; 24: 897-913.
15. Beylot M, Martin C, Laville M, Riou JP, Cohen R, Mornex R. Lipolytic and ketogenic fluxes in human hyperthyroidism. J Clin Endocrinol Metab 1991; 73: 42-9.
16. Engelken SF, Eaton RP. The effects of altered thyroid status on lipid metabolism in the genetic hyperlipemic Zucker rat. Atherosclerosis 1981; 38: 177-88.
17. Ness GC, Lopez D, Chambers CM, Newsome WP, Cornelius P, Long CA, et al. Effects of L-Triiodothyronine and the thyromimetic L-94901 on serum lipoprotein levels and hepatic LDL-receptor, 3-Hydroxy-3-methyglutaryl coenzyme A reductase, and Apo A-I gene expression. Biochem Pharm 1998; 56: 121-9.
18. Casla A, Rovira A, Wells JA, Dohm GL. Increased glucose transporter (GLUT-4) protein expression in hyperthyroidism. Biochem Biophys Res Commun 1990; 171: 182-8.
19. Paget GE, Thorp JM. An effect of thyroxin on the fine structure of the rat liver cell. Nature 1963; 199: 1307-10.
20. 3 increases mitochondrial ATP production in oxidative muscle despite increased expression of UCP2 and -3. Am J Physiol 2001; 280: E761-E69.
21. De Lange P, Lanni A, Beneduce L, Moreno M, Lombardi A, Silvestri E, et al. Uncoupling protein-3 is a molecular determinant for the regulation of resting metabolic rate by thyroid hormone. Endocrinology 2001; 142: 3414-20.
22. Trost S, Swanson E, Gloss B, Wang-Iverson DB, Zhang H, Volodarsky T, et al. The thyroid hormone receptor-beta-selective agonist GC-1 differentially affects plasma lipids and cardiac activity. Endocrinology 2000; 141: 3057-64.
23. Ribeiro MO, Carcalho SD, Schultz JJ, Chiellini G, Scanlan TS, Bianco AC, et al. Thyroid hormone-sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform-specific. J Clin Invest 2001; 108: 97-105.
24. Luboshitzky R, Herer P. Cardiovascular risk factors in middle-aged women with subclinical hypothyroidism. Neuro Endocrinol Lett 2004; 25: 262-6.
25. Perez A, Cubero JM, Sucunza N, Ortega E, Arcelus R, Rodriguez-Espinosa J, et al. Emerging cardiovascular risk factors in subclinical hypothyroidism: lack of change after restoration of euthyroidism. Metabolism 2004; 53: 1512-15.
26. Danesh J, Collins R, Peto R. Lipoprotein (a) and coronary heart disease. Meta-analysis of prospective studies. Circulation 2000; 102: 1082-5.
27. Smallridge RC. Metabolic, physiologic, and clinical indexes of thyroid function. In: The thyroid: a fundamental and clinical text. New York, Lippincot-Raven, 1996; 397-405.
28. Sandler G, Wilson GM. The nature and prognosis of heart disease in thyrotoxicosis. Q J Med 1959; 28: 347-53.
29. Featherstone HJ, Stewart DK. Angina in thyrotoxicosis: thyroid-related coronary artery spasm. Arch Intern Med 1983; 143: 554-60.
30. Ryono DE, Grover GJ, Mellstrom K Thyroid hormones and thyromimetics. In: Burger's Medicinal Chemistry and Drug Discovery (6th Edition, vol 3) Abraham JA (Ed,), Chapter 12.
31. Acotto CG, Niepomniszcze H, Mautalen CA. Estimating body fat and lean tissue distribution in hyperthyroidism by dual-energy X-ray absorptiometry. J Clin Densitom 2002; 5: 305-11.
32. Lonn L, Stenlof K, Ottosson M, Lindroos AK, Nystrom E, Sjostrom L. Body weight and body composition changes after treatment of hyperthyroidism. J Clin Endocrinol Metab 1998; 83: 4269-73.
33. Beylot M, Martin C, Laville M, Riou JP, Cohen P, Mornex R. Lipolytic and ketogenic fluxes in human hyperthyroidism. J Clin Endocrinol Metab 1991; 73: 42-9.
34. Freake JC, Schwartzx HL, Oppenheimer JH. The regulation of lipogenesis by thyroid hormone and its contribution to thermogenesis. Endocrinology 1989; 125: 2868-74.
35. Grover G, Mellstrom K, Ye L, Malm J, Li-Y L, Bladh L, et al. Selective thyroid hormone receptorβ activation: a strategy for reduction of weight, cholesterol, and lipoprotein (a) with reduced cardiovascular liability. Proc Natl Acad Sci USA 2003; 100: 10067-72.
36. Ness GC. Thyroid hormone: Basis for its hypocholesterolemic effect. J Fla Med Assoc 1991; 78: 383-85.
37. Matthaei S, Trost B, Hamann A, Kausch C, Benecke H, Greten H, et al. Effect of in vivo thyroid hormone status on insulin signaling and GLUT1 and GLUT4 transport systems in rat adipocytes. J Endocrinol 1995; 144: 347-57.
38. Mangelsdor DJ, Thummel C, Beato M, Herrlic P, Schulz G, Umesono K, et al. The nuclear receptor superfamily: the second decade. Cell 1995; 83: 838-9.
39. Green S, Kumar V, Theulaz I, Wahli W, Chanbon P. The N-terminal DNA-binding "zinc"finger of the oestrogen and glucocorticoid receptors determines target gene specificity. EMBO J 1988; 7: 3037-44.
40. Lazar MA. Thyroid hormone receptors: multiple forms, multiple possibilities. Endocr Rev 1993; 14: 348-99.
41. Renaud JP, Rochel N, Ruff M, Vivat V, Chambon P, Gronemeyer H, et al. Crystal structure of the RAR-gamma ligand-binding domain bound to all-trans retinoic acid Nature 1995; 378: 681-689.
42. Wagner RL, Apriletti JW, McGrath ME, West BL, Baxter JD, Fletterick RJ. A structural role for hormone in the thyroid hormone receptor. Nature 1995; 378: 690-7.
43. Ribeiro MO, Apriletti JW, Wagner RL, West BL, Feng W, Huber R., et al. Mechanisms of thyroid hormone action: insights from X-ray crystallographic and functional studies. Rec Prog Horm Res 1998; 53: 351-94.
44. Kliewer SA, Umesono K, Noonan DJ, Heyman RA, Evans RM. Convergence of 9-cis retinoic acid and peroxisome proliferators signaling pathways through heterodimer formation of their receptors. Nature 1992; 358: 771-4
45. Leid M, Kastner P, Lyons R, Nakshatri H, Saunders M, Zacharewski T, et al. Purification, cloning and RXR identity of the LeLA cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently. Cell 1992; 68: 377-.
46. Glass CR, Lipkin SM, Devary OV, Rosenfeld MG. Positive and negative regulation of gene transcription by a retinoic acid-thyroid hormone receptor heterodimer. Cell 1989; 59: 697-708.
47. Sharma D, Fondell JD. Temporal formation of distinct thyroid hormone receptor coactivator complexes in HeLa Cells. Mol Endocrinol 2003; 14: 2001-9.
48. Sharma D, Fondell JD. Ordered recruitment of histone acetyltransferaases and the TRAP/Mediator complex to thyroid hormone-responsive promoters in vivo. Proc Soc Natl Acad Sci USA 2002; 99: 7934-39.
49. Stephen ZF, Yurachek EC, Sharif P, Wasvary JM, Leonards KS, Hu CW, et al. Demonstration of potent lipid-lowering activity by a thyromimetic agent devoid of cardiovascular and thermogenic effects. Atherosclerosis 1996; 126: 53-3.
50. Underwood AH, Emmett JC, Ellis D, Flynn SB, Leeson PD, Benson GM, et al. A thyromimetic that decreases plasma cholesterol levels without increasing cardiac activity. Nature 1986; 324: 425-9.
51. Yokoyama N, Walker GN, Main AJ, Stanton JL, Morrissey MM, Boehm C, et al. J Med Chem 1995; 38: 695-99.
52. Hodin RA, Lazar MA, Chin WW. Differential and tissue-specific of the multiple rat c-erbA mRNA species by thyroid hormone. J Clin Invest 1990; 68: 397-440.
53. Hodin RA, Lazar MA, Chin WW. Differential and tissue-specific of the multiple rat c-erbA mRNA species by thyroid hormone. J Clin Invest 1990; 68: 397-440.
54. Johansson C, Vennström B, Thoren P. Evidence that decreased heart rate in thyroid hormone receptor-a1-deficient mice is an intrinsic defect. Am J Physiol 1998; 275: R640-6.
55. Forrest D, Vennström B. Functions of thyroid hormone receptors in mice. Thyroid 2000; 10: 41-52.
56. Wikström L, Johansson C, Salto C, Barlow C, Campos, Barros A, et al. Abnormal heart rate and body temperature in mice lacking thyroid hormone receptor alpha-1. EMBO J 1998; 17: 455-61.
57. Moore JMR, Galicia SJ, McReynolds AC, Nguyen N-H, Scanlan TS, Guy RK. Quantitative proteomics of the thyroid hormone receptor-coregulator interactions. J Biol Chem 2004; 279: 27584-90.
58. Jorgensen CH. In: Li CH Ed, Hormonal Proteins and Peptides, Thyroid hormones and analogs. II. Structure-activity relationships. New York, Academic Press. 1978; 6: 107-204.
59. Ellis D, Emmett JC, Leeson PD, Underwood AH. In Vederame M Ed, Handbook of Hormones, Vitamins and Radiopaques. Boca Raton, CRC Press. 1986; 94.
60. Leeson PD, Underwood AH. In Emmett JC Ed, Comprehensive Medicinal Chemistry, Thyroid Hormone Receptors. Oxford, London, Pergamon Press 1990; 3: 1145-73.
61. Chiellini G, Apriletti JW, Yosihhara HA, Baxter JD, Ribeiro RCJ, Scanlan TS. A high-affinity subtype-selective agonist ligand for the thyroid hormone receptor. Chem Biol 1998; 5: 299-306.
62. Grover GJ, Egan D, Sleph PG, Beehler BC, Chiellini G, Ngoc-Ha N, et al. Effects of the thyroid hormone receptor agonist GC-1 on metabolic rate and cholesterol in rats and primates: selective actions relative to 3,5,3′-Triiodo-thyronine. Endocrinology 2004; 145: 1656-61.
63. 1. J Med Chem 2003; 45: 1580-8.
64. Baxter JD, Goede P, Apriletti FW. Structure-based design and synthesis of a thyroid hormone receptor (TR) antagonist. Endocrinology 2002; 143:517-4.
65. Novitzky D, Cooper DKC, Barton CI, Greer A, Chaffin J, Grim J, et al. Triiodothyronine as an inotropic agent after open heart surgery. J Throac Cardiovasc Surg 1989; 98: 972-8.
66. Malm J. Thyroid hormone ligands and metabolic diseases. Curr Pharmaceut Des 2004; 10: 3525-32.
67. Hangeland JJ, Doweyko AM, Dejneka T, Friends TJ, Devasthale P, Mellstrom K, et al. Thyroid Receptor Ligands, Part 2: Thyromimetics with Improved Selectivity for the Thyroid Hormone Receptor Beta. Bioorg Med Chem Lett 2004; 14: 3549-53.
68. Dow RL, Schnelier SR, Paight ES, Hank RF, Chiang P, Cornelius P. Discovery of a Novel Series of 6-Azauracil-Based Thyroid Hormone Receptor Ligands. Potent, TRβ Subtype-Selective Thyromimetics. Bioorg Med Chem Lett 2003; 13: 379-82.
69. Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med 2001; 344: 501-9.
70. Gloss B, Trost S. Bluhm W, Swanson E, Clark R, Winkfein R, et al. Cardiac ion channel expression and contractile function in mice with deletion of thyroid hormone receptor alpha or beta. Endocrinology 2001; 142: 544-50.
71. Carlsson B, Singh BN, Temciuc M, Nilsson S, Li YL, Mellin C, et al. Synthesis and preliminary characterization of a novel aniarrhythmic compound (KB-130015) with an improved toxicity profile compared with amiodarone. J Med Chem 2002; 45: 623-30.
72. Chalmers DK, Munro SLA, Iskander MN, Craik DJ. Models for the binding of amiodarone to the thyroid hormone receptor. Comput Aided Mol Des 1992; 6: 19-31.
73. Van Beeren GC, Jong WM, Kaptein E, Visser TJ, Bakker O, Wiersinga WM. Dronerarone acts as a selective inhibitor of 3,5,3′-triiodothyronine binding to thyroid hormone receptor-α1: in vitro and in vivo evidence. Endocrinology 2003; 144: 552-8.