TY - JOUR
T1 - Approaches to the rational design of selective melanocortin receptor antagonists
AU - Hruby, Victor J.
AU - Cai, Minying
AU - Nyberg, Joel
AU - Muthu, Dhanasekaran
N1 - Funding Information:
The research reported from our laboratory has primarily been supported by a grant from the National Institutes of Health (DK17420).
PY - 2011/5
Y1 - 2011/5
N2 - Introduction: When establishing the physiological roles of specific receptors in normal and disease states, it is critical to have selective antagonist ligands for each receptor in a receptor system with several subtypes. The melanocortin receptors have five subtypes referred to as the melanocortin 1 receptor, melanocortin 2 receptor, melanocortin 3 receptor, melanocortin 4 receptor and melanocortin 5 receptor, and they are of critical importance for many aspects of human health and disease. Areas covered: This article reviews the current efforts to design selective antagonistic ligands for the five human melanocortin receptors summarizing the currently published orthosteric and allosteric antagonists for each of these receptors. Expert opinion: Though there has been progress, there are still few drugs available that address the many significant biological activities and diseases that are associated with these receptors, which is possibly due to the lack of receptor selectivity that these designed ligands are currently showing. The authors believe that further studies into the antagonists' 3D conformational and topographical properties in addition to future mutagenesis studies will provide greater insight into these ligands which could play a role in the treatment of various diseases in the future.
AB - Introduction: When establishing the physiological roles of specific receptors in normal and disease states, it is critical to have selective antagonist ligands for each receptor in a receptor system with several subtypes. The melanocortin receptors have five subtypes referred to as the melanocortin 1 receptor, melanocortin 2 receptor, melanocortin 3 receptor, melanocortin 4 receptor and melanocortin 5 receptor, and they are of critical importance for many aspects of human health and disease. Areas covered: This article reviews the current efforts to design selective antagonistic ligands for the five human melanocortin receptors summarizing the currently published orthosteric and allosteric antagonists for each of these receptors. Expert opinion: Though there has been progress, there are still few drugs available that address the many significant biological activities and diseases that are associated with these receptors, which is possibly due to the lack of receptor selectivity that these designed ligands are currently showing. The authors believe that further studies into the antagonists' 3D conformational and topographical properties in addition to future mutagenesis studies will provide greater insight into these ligands which could play a role in the treatment of various diseases in the future.
KW - allosteric antagonist
KW - melanocortin receptors
KW - orthosteric antagonists
KW - receptor antagonists
UR - http://www.scopus.com/inward/record.url?scp=79955404363&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955404363&partnerID=8YFLogxK
U2 - 10.1517/17460441.2011.565743
DO - 10.1517/17460441.2011.565743
M3 - Review article
C2 - 22646078
AN - SCOPUS:79955404363
SN - 1746-0441
VL - 6
SP - 543
EP - 557
JO - Expert Opinion on Drug Discovery
JF - Expert Opinion on Drug Discovery
IS - 5
ER -