TY - JOUR
T1 - MC4R Agonists
T2 - Structural Overview on Antiobesity Therapeutics
AU - Gonçalves, Juliana
AU - Palmer, Daniel
AU - Meldal, Morten Peter
PY - 2018/4
Y1 - 2018/4
N2 - The melanocortin-4 receptor (MC4R) regulates adipose tissue formation and energy homeostasis, and is believed to be a monogenic target for novel antiobesity therapeutics. Several research efforts targeting this receptor have identified potent and selective agonists. While viable agonists have been characterized in vitro, undesirable side effects frequently appeared during clinical trials. The most promising candidates have diverse structures, including linear peptides, cyclic peptides, and small molecules. Herein, we present a compilation of potent MC4R agonists and discuss the pivotal structural differences within those molecules that resulted in good selectivity for MC4R over other melanocortins. We provide insight on recent progress in the field and reflect on directions for development of new agonists.
AB - The melanocortin-4 receptor (MC4R) regulates adipose tissue formation and energy homeostasis, and is believed to be a monogenic target for novel antiobesity therapeutics. Several research efforts targeting this receptor have identified potent and selective agonists. While viable agonists have been characterized in vitro, undesirable side effects frequently appeared during clinical trials. The most promising candidates have diverse structures, including linear peptides, cyclic peptides, and small molecules. Herein, we present a compilation of potent MC4R agonists and discuss the pivotal structural differences within those molecules that resulted in good selectivity for MC4R over other melanocortins. We provide insight on recent progress in the field and reflect on directions for development of new agonists.
U2 - 10.1016/j.tips.2018.01.004
DO - 10.1016/j.tips.2018.01.004
M3 - Review
C2 - 29478721
SN - 0165-6147
VL - 39
SP - 402
EP - 423
JO - Trends in Pharmacological Sciences
JF - Trends in Pharmacological Sciences
IS - 4
ER -