Discovery of a beta-MSH-derived MC-4R selective agonist.
A series of novel, disulfide-constrained human beta-melanocyte stimulating hormone (beta-MSH)-derived peptides were optimized for in vitro melanocortin-4 receptor (MC-4R) binding affinity, agonist efficacy, and selectivity. The most promising of these, analogue 18, was further studied in vivo using chronic rat food intake and body weight models.
Mayer
John P
JP
Lilly Research Laboratories, A Division of Eli Lilly and Co., Lilly Corporate Center, Indianapolis, Indiana 46285, USA. j.mayer@lilly.com
Hsiung
Hansen M
HM
Flora
David B
DB
Edwards
Patrick
P
Smith
Dennis P
DP
Zhang
Xing-Yue
XY
Gadski
Robert A
RA
Heiman
Mark L
ML
Hertel
Jeanne L
JL
Emmerson
Paul J
PJ
Husain
Saba
S
O'brien
Thomas P
TP
Kahl
Steven D
SD
Smiley
David L
DL
Zhang
Lianshan
L
Dimarchi
Richard D
RD
Yan
Liang Zeng
LZ
D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D004435:Eating / Q000187:drug effects; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists*; D013329:Structure-Activity Relationship; D019824:beta-MSH / Q000737:chemistry*
D019440:Anti-Obesity Agents; D009842:Oligopeptides; D044105:Receptor, Melanocortin, Type 4; D019824:beta-MSH