MC1 receptor agonist,potent and selective
CAS：457893-92-4
分子式：C32H41N5O4.2HCl
分子量：632.62
纯度：98%
存储：Store at -20°C

Background:

BMS 470539 dihydrochloride is a potent and selective melanocortin-1 (MC1) receptor agonist with IC50 of 120 nM [1].
The melanocortin-1 receptor (MC-1R) is a G protein-coupled receptor involved in blocking inflammation and augmenting skin pigmentation [1].
In human melanoma cells, which endogenously express MC-1R, BMS-470539 inhibited TNF- -induced activation of a NF-κB transcriptional reporter in a dose-dependent way.
In a murine LPS (lipopolysaccharide) induced cytokine accumulation model, BMS 470539 dihydrochloride reduced TNF-α levels by 65% and 82% at 11umol/kg and 33umol/kg respectively in a dose-dependent way [1]. In a murine lung inflammation model, BMS 470539 (15umol/kg) reduced LPS-induced leukocyte infiltration (comprised primarily of neutrophils) by 45%. In a delayed-type hypersensitivity model, BMS 470539 reduced paw swelling by 59% [2]. In mice with IR, BMS 470539 (doses of 6.16 and 18.47 mg/kg) significantly inhibited leucocyte adhesion and emigration in a dose-dependent way. In the cremasteric microcirculation inflamed by platelet-activating factor, BMS-470539 inhibited cell emigration, but did not affect cell adhesion [3].
参考文献:
[1]. Herpin TF, Yu G, Carlson KE, et al. Discovery of tyrosine-based potent and selective melanocortin-1 receptor small-molecule agonists with anti-inflammatory properties. J Med Chem, 2003, 46(7): 1123-1126.
[2]. Kang L, McIntyre KW, Gillooly KM, et al. A selective small molecule agonist of the melanocortin-1 receptor inhibits lipopolysaccharide-induced cytokine accumulation and leukocyte infiltration in mice. J Leukoc Biol, 2006, 80(4): 897-904.
[3]. Leoni G, Voisin MB, Carlson K, et al. The melanocortin MC(1) receptor agonist BMS-470539 inhibits leucocyte trafficking in the inflamed vasculature. Br J Pharmacol, 2010, 160(1): 171-180.