Targeting melanocortin receptors: an approach to treat weight disorders and sexual dysfunction

被引：100

作者：

Wikberg, Jarl E. S. ^{[1
]}

Mutulis, Felikss ^{[1
]}

机构：

[1] Uppsala Univ, Div Pharmacol, Dept Pharmaceut Biosci, SE-75124 Uppsala, Sweden

来源：

NATURE REVIEWS DRUG DISCOVERY | 2008年 / 7卷 / 04期

关键词：

D O I：

10.1038/nrd2331

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The melanocortin system has multifaceted roles in the control of body weight homeostasis, sexual behaviour and autonomic functions, and so targeting this pathway has immense promise for drug discovery across multiple therapeutic areas. In this Review, we first outline the physiological roles of the melanocortin system, then discuss the potential of targeting melanocortin receptors by using MC3 and MC4 agonists for treating weight disorders and sexual dysfunction, and MC 4 antagonists to treat anorectic and cachectic conditions. Given the complexity of the melanocortin system, we also highlight the challenges and opportunities for future drug discovery in this area.

引用

页码：307 / 323

页数：17

共 272 条

[1] Inverse agonism gains weight [J].

Adan, RAH ;

Kas, MJH .

TRENDS IN PHARMACOLOGICAL SCIENCES, 2003, 24 (06) :315-321

[2] POTENT AND PROLONGED ACTING CYCLIC LACTAM ANALOGS OF ALPHA-MELANOTROPIN - DESIGN BASED ON MOLECULAR-DYNAMICS [J].

ALOBEIDI, F ;

CASTRUCCI, AMD ;

HADLEY, ME ;

HRUBY, VJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1989, 32 (12) :2555-2561

[3] Quantitative measurement of the levels of melanocortin receptor subtype 1, 2, 3 and 5 and pro-opio-melanocortin peptide gene expression in subsets of human peripheral blood leucocytes [J].

Andersen, GN ;

Hägglund, M ;

Nagaeva, O ;

Frängsmyr, L ;

Petrovska, R ;

Mincheva-Nilsson, L ;

Wikberg, JES .

SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 2005, 61 (03) :279-284

[4] MC1 receptors are constitutively expressed on leucocyte subpopulations with antigen presenting and cytotoxic functions [J].

Andersen, GN ;

Nagaeva, O ;

Mandrika, I ;

Petrovska, R ;

Muceniece, R ;

Mincheva-Nilsson, L ;

Wikberg, JES .

CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2001, 126 (03) :441-446

[5]

[Anonymous], 2004, CHEMOGENOMICS DRUG D, DOI DOI 10.1002/3527603948.CH10

[6] ACTH- and α-MSH-induced grooming, stretching, yawning and penile erection in male rats:: Site of action in the brain and role of melanocortin receptors [J].

Argiolas, A ;

Melis, MR ;

Murgia, S ;

Schlöth, HB .

BRAIN RESEARCH BULLETIN, 2000, 51 (05) :425-431

[7] A polymorphism in the human agouti-related protein is associated with late-onset obesity [J].

Argyropoulos, G ;

Rankinen, T ;

Neufeld, DR ;

Rice, T ;

Province, MA ;

Leon, AS ;

Skinner, JS ;

Wilmore, JH ;

Rao, DC ;

Bouchard, C .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2002, 87 (09) :4198-4202

[8]

ASTELLAS PHARM INC, 2005, Patent No. 2005047253

[9] Functional dimorphism of two hAgRP promoter SNPs in linkage disequilibrium [J].

Bai, F ;

Rankinen, T ;

Charbonneau, C ;

Belsham, DD ;

Rao, DC ;

Bouchard, C ;

Argyropoulos, G .

JOURNAL OF MEDICAL GENETICS, 2004, 41 (05) :350-353

[10] Optimization of a privileged structure leading to potent and selective human melanocortin subtype-4 receptor ligands [J].

Bakshi, RK ;

Hong, QM ;

Tang, R ;

Kalyani, RN ;

MacNeil, T ;

Weinberg, DH ;

Van der Ploeg, LHT ;

Patchett, AA ;

Nargund, RP .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (05) :1130-1133

← 1 2 3 4 5 6 7 8 9 10 →