Assessment of a small molecule melanocortin-4 receptor-specific agonist on energy homeostasis

Brain Research

Volumn 1000, Issue 1-2, 2004, Pages 64-71

  Cepoi, David ^a   Phillips, Teresa ^b   Cismowski, Mary ^b   Goodfellow, Val S ^b   Ling, Nick ^b   Cone, Roger D ^a   Fan, Wei ^a  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^b NEUROCRINE BIOSCIENCES INC   (United States)

Author keywords

Feeding; Ingestive behaviors; Melanocortin receptor; Neural basis of behavior; Obesity; POMC; Small molecule agonist

Indexed keywords

4 TETRAHYDROISOQUINOLINE 3 CARBOXYLIC ACID [(4 CHLOROBENZYL) 2 (4 CYCLOHEXYL 4 [1,2,4]TRIAZOL 1 YLMETHYLPIPERIDIN 1 YL) 2 OXOETHYL]AMIDE; INSULIN; ISOQUINOLINE DERIVATIVE; MELANOCORTIN 4 RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG EFFECT; DRUG POTENCY; DRUG PURIFICATION; DRUG STRUCTURE; DRUG SYNTHESIS; EMBRYO; FEEDING BEHAVIOR; HOMEOSTASIS; HUMAN; HUMAN CELL; IN VITRO STUDY; INSULIN RELEASE; KNOCKOUT MOUSE; MALE; METABOLIC RATE; MOUSE; NONHUMAN; PRIORITY JOURNAL;

ANIMALS; CELL LINE; EATING; ENERGY METABOLISM; HOMEOSTASIS; HUMANS; MALE; MICE; MICE, KNOCKOUT; RECEPTOR, MELANOCORTIN, TYPE 4; TETRAHYDROISOQUINOLINES; TRIAZOLES;

EID: 1842453288     PISSN: 00068993     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.brainres.2003.10.041     Document Type: Article

References (28)

1. Bagnol D., Lu X.Y., Kaelin C.B., Day H.E., Ollmann M., Gantz I., Akil H., Barsh G.S., Watson S.J. Anatomy of an endogenous antagonist: relationship between agouti-related protein and proopiomelanocortin in brain. J. Neurosci. 19:1999;RC26.
2. Benoit S.C., Schwartz M.W., Lachey J.L., Hagan M.M., Rushing P.A., Blake K.A., Yagaloff K.A., Kurylko G., Franco L., Danhoo W., Seeley R.J. A novel selective melanocortin-4 receptor agonist reduces food intake in rats and mice without producing aversive consequences. J. Neurosci. 20:2000;3442-3448.
3. Bray G.A., Greenway F.L. Current and potential drugs for treatment of obesity. Endocr. Rev. 20:1999;805-875.
4. Butler A.A., Kesterson R.A., Khong K., Cullen M.J., Pelleymounter M.A., Dekoning J., Baetscher M., Cone R.D. A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology. 141:2000;3518-3521.
5. Butler A.A., Marks D.L., Fan W., Kuhn C.M., Bartolome M., Cone R.D. Melanocortin-4 receptor is required for acute homeostatic responses to increased dietary fat. Nat. Neurosci. 4:2001;605-611.
6. Chen A.S., Marsh D.J., Trumbauer M.E., Frazier E.G., Guan X.M., Yu H., Rosenblum C.I., Vongs A., Feng Y., Cao L., Metzger J.M., Strack A.M., Camacho R.E., Mellin T.N., Nunes C.N., Min W., Fisher J., Gopal-Truter S., MacIntyre D.E., Chen H.Y., Van der Ploeg L.H. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat. Genet. 26:2000;97-102.
7. Cowley M.A., Pronchuk N., Fan W., Dinulescu D.M., Colmers W.F., Cone R.D. Integration of NPY, AGRP, and melanocortin signals in the hypothalamic paraventricular nucleus: evidence of a cellular basis for the adipostat. Neuron. 24:1999;155-163.
8. De Souza J., Butler A.A., Cone R.D. Disproportionate inhibition of feeding in A(y) mice by certain stressors: a cautionary note. Neuroendocrinology. 72:2000;126-132.
9. Fan W., Boston B.A., Kesterson R.A., Hruby V.J., Cone R.D. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature. 385:1997;165-168.
10. Fan W., Dinulescu D.M., Butler A.A., Zhou J., Marks D.L., Cone R.D. The central melanocortin system can directly regulate serum insulin levels. Endocrinology. 141:2000;3072-3079.
11. Fong T.M., Mao C., MacNeil T., Kalyani R., Smith T., Weinberg D., Tota M.R., Van der Ploeg L.H. ART (protein product of agouti-related transcript) as an antagonist of MC-3 and MC-4 receptors. Biochem. Biophys. Res. Commun. 237:1997;629-631.
12. Franklin K.B.J., Paxinos G. The Mouse Brain in Stereotaxic Coordinates. 1997;Academic Press, San Diego.
13. Giraudo S.Q., Billington C.J., Levine A.S. Feeding effects of hypothalamic injection of melanocortin 4 receptor ligands. Brain Res. 809:1998;302-306.
14. Grieco P., Balse P.M., Weinberg D., MacNeil T., Hruby V.J. D-Amino acid scan of gamma-melanocyte-stimulating hormone: importance of Trp(8) on human MC3 receptor selectivity. J. Med. Chem. 43:2000;4998-5002.
15. Haynes W.G., Morgan D.A., Djalali A., Sivitz W.I., Mark A.L. Interactions between the melanocortin system and leptin in control of sympathetic nerve traffic. Hypertension. 33:1999;542-547.
16. Huszar D., Lynch C.A., Fairchild-Huntress V., Dunmore J.H., Fang Q., Berkemeier L.R., Gu W., Kesterson R.A., Boston B.A., Cone R.D., Smith F.J., Campfield L.A., Burn P., Lee F. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell. 88:1997;131-141.
17. Lu D., Willard D., Patel I.R., Kadwell S., Overton L., Kost T., Luther M., Chen W., Woychik R.P., Wilkison W.O., et al. Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature. 371:1994;799-802.
18. Marsh D.J., Hollopeter G., Huszar D., Laufer R., Yagaloff K.A., Fisher S.L., Burn P., Palmiter R.D. Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides. Nat. Genet. 21:1999;119-122.
19. Mizuno T.M., Makimura H., Silverstein J., Roberts J.L., Lopingco T., Mobbs C.V. Fasting regulates hypothalamic neuropeptide Y, agouti-related peptide, and proopiomelanocortin in diabetic mice independent of changes in leptin or insulin. Endocrinology. 140:1999;4551-4557.
20. Mountjoy K.G., Robbins L.S., Mortrud M.T., Cone R.D. The cloning of a family of genes that encode the melanocortin receptors. Science. 257:1992;1248-1251.
21. Mountjoy K.G., Mortrud M.T., Low M.J., Simerly R.B., Cone R.D. Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol. Endocrinol. 8:1994;1298-1308.
22. Ollmann M.M., Wilson B.D., Yang Y.K., Kerns J.A., Chen Y., Gantz I., Barsh G.S. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science. 278:1997;135-138.
23. A.A. Pachett, Abstracts of Papers, Medicinal Chemistry Section, American Chemical Society meeting, Chicago, 2001, p. 152.
24. Robinson S.W., Dinulescu D.M., Cone R.D. Genetic models of obesity and energy balance in the mouse. Annu. Rev. Genet. 34:2000;687-745.
25. Sawchenko P.E. Toward a new neurobiology of energy balance, appetite, and obesity: the anatomists weigh in. J. Comp. Neurol. 402:1998;435-441.
26. Sebhat I.K., Martin W.J., Ye Z., Barakat K., Mosley R.T., Johnston D.B., Bakshi R., Palucki B., Weinberg D.H., MacNeil T., Kalyani R.N., Tang R., Stearns R.A., Miller R.R., Tamvakopoulos C., Strack A.M., McGowan E., Cashen D.E., Drisko J.E., Hom G.J., Howard A.D., MacIntyre D.E., van der Ploeg L.H., Patchett A.A., Nargund R.P. Design and pharmacology of N-[(3R)-1,2,3,4- tetrahydroisoquinolinium-3-ylcarbonyl]-(1R)-1-(4-chlorobenzyl) -2-[4-cyclohexyl-4-(1H-1,2,4-triazol-1-ylmethyl)piperidin-1-yl]-2-oxoethylamine (1), a potent, selective, melanocortin subtype-4 receptor agonist. J. Med. Chem. 45:2002;4589-4593.
27. Spiegelman B.M., Flier J.S. Obesity and the regulation of energy balance. Cell. 104:2001;531-543.
28. Van der Ploeg L.H., Martin W.J., Howard A.D., Nargund R.P., Austin C.P., Guan X., Drisko J., Cashen D., Sebhat I., Patchett A.A., Figueroa D.J., DiLella A.G., Connolly B.M., Weinberg D.H., Tan C.P., Palyha O.C., Pong S.S., MacNeil T., Rosenblum C., Vongs A., Tang R., Yu H., Sailer A.W., Fong T.M., Huang C., Tota M.R., Chang R.S., Stearns R., Tamvakopoulos C., Christ G., Drazen D.L., Spar B.D., Nelson R.J., MacIntyre D.E. A role for the melanocortin 4 receptor in sexual function. Proc. Natl. Acad. Sci. USA. 99:2002;11381-11386.