Back to Search
Start Over
Novel approaches to the design of bioavailable melanotropins.
- Source :
-
Expert opinion on drug discovery [Expert Opin Drug Discov] 2017 Oct; Vol. 12 (10), pp. 1023-1030. Date of Electronic Publication: 2017 Jul 12. - Publication Year :
- 2017
-
Abstract
- Introduction: The melanocortin system is a primordial and critical system for survival, involved in a wide variety of physiological functions. It includes melanocortin receptors (MCRs) and melanotropin ligands (MCLs). MCRs are important drug targets that can regulate several key physiological processes. Extensive efforts have been made to develop peptide and peptidomimetics targeting melanocortin receptors including MC1R, MC3R, MC4R and MC5R. Most research is focused on developing potent and selective melanotropins. However, developing bioavailable melanotropins remains challenging. Areas covered: Herein, the authors summarize promising strategies for developing bioavailable MCLs by using cyclized N-methylated melanotropins, and using cyclotide and tetrapeptide as templates. They discuss their unique advantages in oral availability and targeting MCRs in the central nervous system or in peripheral tissues. Finally, they discuss the observed differences in thepharmacology of MCRs between in vitro and in vivo tests. Expert opinion: N-methylated cyclized melanotropins have great potential to become bio- available drugs targeting MCRs in the brain, while MCR-grafted cyclotides tend to target MCRs in peripheral tissue. A better understanding of the biased signaling process is a new challenge and opportunity for the future discovery of bioavailable MCLs.
- Subjects :
- Animals
Biological Availability
Cyclotides chemical synthesis
Cyclotides pharmacokinetics
Cyclotides pharmacology
Humans
Ligands
Melanocyte-Stimulating Hormones chemistry
Melanocyte-Stimulating Hormones pharmacokinetics
Peptides chemical synthesis
Peptides pharmacokinetics
Peptides pharmacology
Peptidomimetics chemical synthesis
Peptidomimetics pharmacokinetics
Peptidomimetics pharmacology
Tissue Distribution
Drug Design
Melanocyte-Stimulating Hormones chemical synthesis
Receptors, Melanocortin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1746-045X
- Volume :
- 12
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Expert opinion on drug discovery
- Publication Type :
- Academic Journal
- Accession number :
- 28699792
- Full Text :
- https://doi.org/10.1080/17460441.2017.1351940