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Hruby VJ, Cai M, Nyberg J, et al. Approaches to the rational design of selective melanocortin receptor antagonists. Expert Opin Drug Discov. 2011;6(5):543-57doi: 10.1517/17460441.2011.565743.
Hruby, V. J., Cai, M., Nyberg, J., & Muthu, D. (2011). Approaches to the rational design of selective melanocortin receptor antagonists. Expert opinion on drug discovery, 6(5), 543-57. https://doi.org/10.1517/17460441.2011.565743
Hruby, Victor J, et al. "Approaches to the rational design of selective melanocortin receptor antagonists." Expert opinion on drug discovery vol. 6,5 (2011): 543-57. doi: https://doi.org/10.1517/17460441.2011.565743
Hruby VJ, Cai M, Nyberg J, Muthu D. Approaches to the rational design of selective melanocortin receptor antagonists. Expert Opin Drug Discov. 2011 May;6(5):543-57. doi: 10.1517/17460441.2011.565743. Epub 2011 Mar 24. PMID: 22646078; PMCID: PMC4608743.
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Expert Opin Drug Discov. 2011 May;6(5):543-57. doi: 10.1517/17460441.2011.565743. Epub 2011 Mar 24.

Approaches to the rational design of selective melanocortin receptor antagonists.

Expert opinion on drug discovery

Victor J Hruby, Minying Cai, Joel Nyberg, Dhanasekaran Muthu

Affiliations

  1. University of Arizona, Department of Chemistry and Biochemistry , 1306 E. University Blvd., Tucson, AZ 85721 , USA [email protected].

PMID: 22646078 PMCID: PMC4608743 DOI: 10.1517/17460441.2011.565743

Abstract

INTRODUCTION: When establishing the physiological roles of specific receptors in normal and disease states, it is critical to have selective antagonist ligands for each receptor in a receptor system with several subtypes. The melanocortin receptors have five subtypes referred to as the melanocortin 1 receptor, melanocortin 2 receptor, melanocortin 3 receptor, melanocortin 4 receptor and melanocortin 5 receptor, and they are of critical importance for many aspects of human health and disease.

AREAS COVERED: This article reviews the current efforts to design selective antagonistic ligands for the five human melanocortin receptors summarizing the currently published orthosteric and allosteric antagonists for each of these receptors.

EXPERT OPINION: Though there has been progress, there are still few drugs available that address the many significant biological activities and diseases that are associated with these receptors, which is possibly due to the lack of receptor selectivity that these designed ligands are currently showing. The authors believe that further studies into the antagonists' 3D conformational and topographical properties in addition to future mutagenesis studies will provide greater insight into these ligands which could play a role in the treatment of various diseases in the future.

References

  1. J Med Chem. 2002 Nov 21;45(24):5287-94 - PubMed
  2. Endocrinology. 1996 Aug;137(8):3291-4 - PubMed
  3. Am J Clin Nutr. 2007 Apr;85(4):950-3 - PubMed
  4. J Med Chem. 2008 May 8;51(9):2701-7 - PubMed
  5. Nature. 1997 Jan 9;385(6612):165-8 - PubMed
  6. Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4867-72 - PubMed
  7. Life Sci. 1982 Jul 19;31(3):189-99 - PubMed
  8. Peptides. 2007 Jun;28(6):1191-6 - PubMed
  9. Bioorg Med Chem Lett. 2005 May 16;15(10):2541-6 - PubMed
  10. J Med Chem. 2003 Aug 14;46(17):3728-33 - PubMed
  11. Med Res Rev. 1982 Jul-Sep;2(3):247-70 - PubMed
  12. J Med Chem. 2002 Jun 6;45(12):2644-50 - PubMed
  13. Curr Top Med Chem. 2007;7(11):1098-1106 - PubMed
  14. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5754-8 - PubMed
  15. Anesthesiology. 2005 Mar;102(3):509-14 - PubMed
  16. J Med Chem. 1989 Dec;32(12):2555-61 - PubMed
  17. Peptides. 2006 Feb;27(2):259-64 - PubMed
  18. Endocrinology. 2000 Sep;141(9):3518-21 - PubMed
  19. Neurosci Lett. 2004 Mar 25;358(2):79-82 - PubMed
  20. J Med Chem. 2005 Mar 24;48(6):1839-48 - PubMed
  21. Bioorg Med Chem Lett. 2006 Oct 15;16(20):5462-7 - PubMed
  22. Chem Biol Drug Des. 2006 May;67(5):329-35 - PubMed
  23. Mol Endocrinol. 1994 Oct;8(10):1298-308 - PubMed
  24. J Med Chem. 2003 Feb 27;46(5):810-9 - PubMed
  25. Urology. 2000 Oct 1;56(4):641-6 - PubMed
  26. J Neurosci. 1996 Aug 15;16(16):5182-8 - PubMed
  27. Anesthesiology. 2010 Jan;112(1):181-8 - PubMed
  28. J Med Chem. 1995 Sep 1;38(18):3454-61 - PubMed
  29. J Med Chem. 2008 Jan 24;51(2):187-95 - PubMed
  30. Bioorg Khim. 2008 Jan-Feb;34(1):29-35 - PubMed
  31. Ann N Y Acad Sci. 1977 Oct 28;297:1-664 - PubMed
  32. Cell. 1997 Dec 12;91(6):789-98 - PubMed
  33. Br J Pharmacol. 1999 Jan;126(1):27-34 - PubMed
  34. J Neurosci. 2008 Nov 26;28(48):12946-55 - PubMed
  35. J Am Chem Soc. 2010 Jun 16;132(23):8115-28 - PubMed
  36. Endocrinology. 1998 Dec;139(12):5006-14 - PubMed
  37. Methods Enzymol. 1975;39:347-59 - PubMed
  38. J Med Chem. 2006 Mar 23;49(6):1946-52 - PubMed
  39. Regul Pept. 2009 Jun 5;155(1-3):46-54 - PubMed
  40. Neuroreport. 1995 Nov 13;6(16):2193-6 - PubMed
  41. J Med Chem. 2003 Nov 6;46(23):4965-73 - PubMed
  42. J Med Chem. 2001 Oct 25;44(22):3665-72 - PubMed
  43. Int J Pept Protein Res. 1990 Mar;35(3):228-34 - PubMed
  44. Biochem J. 1990 Jun 1;268(2):249-62 - PubMed
  45. Endocr Rev. 2006 Dec;27(7):736-49 - PubMed
  46. Br J Pharmacol. 1998 May;124(1):75-82 - PubMed
  47. J Med Chem. 2006 Nov 16;49(23):6888-96 - PubMed
  48. Bioorg Med Chem Lett. 2006 Apr 15;16(8):2302-5 - PubMed
  49. J Leukoc Biol. 2004 Oct;76(4):845-53 - PubMed
  50. Bioorg Med Chem Lett. 2005 Jul 15;15(14):3434-8 - PubMed
  51. J Biol Chem. 2007 Jul 27;282(30):21712-9 - PubMed
  52. J Neurochem. 2007 May;101(4):1145-52 - PubMed
  53. Biochemistry. 1994 Apr 19;33(15):4543-9 - PubMed
  54. Bioorg Med Chem Lett. 2007 Dec 1;17(23):6546-52 - PubMed
  55. Endocrinology. 2007 Dec;148(12):6186-94 - PubMed
  56. J Hypertens. 2006 Nov;24(11):2239-46 - PubMed
  57. J Urol. 1998 Aug;160(2):389-93 - PubMed
  58. Eur J Pharmacol. 2003 Aug 1;474(1):95-101 - PubMed
  59. Methods Enzymol. 2002;343:49-72 - PubMed
  60. Int Arch Allergy Immunol. 2010;153(1):13-8 - PubMed
  61. Proc Natl Acad Sci U S A. 1974 Jan;71(1):80-3 - PubMed
  62. Pharmacol Biochem Behav. 2005 Dec;82(4):621-6 - PubMed
  63. Biopolymers. 1997;43(3):219-66 - PubMed
  64. Bioorg Med Chem Lett. 2007 May 1;17(9):2492-8 - PubMed
  65. J Pharmacol Exp Ther. 2003 Feb;304(2):818-26 - PubMed
  66. Nat Rev Drug Discov. 2002 Nov;1(11):847-58 - PubMed

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