Discovery of tyrosine-based potent and selective melanocortin-1 receptor small-molecule agonists with anti-inflammatory properties.
The melanocortin-1 receptor (MC-1R) is a G-protein-coupled receptor involved in inflammation and skin pigmentation. Compound 2 is the first highly potent and selective MC-1R small-molecule agonist reported. Compound 2 showed efficacy in an acute model of inflammation, which has demonstrated the role of MC-1R in modulation of inflammation.
Herpin
Timothy F
TF
Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 5400, Princeton, New Jersey 08543, USA.
Yu
Guixue
G
Carlson
Kenneth E
KE
Morton
George C
GC
Wu
Ximao
X
Kang
Liya
L
Tuerdi
Huji
H
Khanna
Ashish
A
Tokarski
John S
JS
Lawrence
R Michael
RM
Macor
John E
JE
D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008070:Lipopolysaccharides; D051379:Mice; D008807:Mice, Inbred BALB C; D018043:Receptors, Corticotropin / Q000819:agonists*; D044101:Receptors, Melanocortin; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine