Cyclic analogue design
Seven cyclic lactam analogues of alpha-MSH(4-13) and alpha-MSH(4-10) were synthesised and compared in frog and lizard skin bioassays, examining how ring size affected potency and prolonged activity1.
Sources [1]
Research Peptide · For laboratory research use only
MT-2
Also known as Melanotan II
- Formula
- C50H69N15O9
- CAS
- 121062-08-6
Available as
Certificates of analysis
Overview
MT-2 (melanotan II, MTII) is a cyclic lactam analogue of alpha-MSH, Ac-[Nle4, Asp5, D-Phe7, Lys10]-alpha-MSH(4-10)-NH2, in which a lactam bridge links the side chains of aspartic acid 5 and lysine 10 to form a 23-membered ring. It was described in 1989 as part of a series of cyclic alpha-MSH fragment analogues designed using molecular dynamics1.
Melanotan II is an agonist at the neural MC3 and MC4 melanocortin receptors and has been used as a research tool for the central melanocortin system2,3. Rodent studies have examined feeding behaviour, energy expenditure and grooming2,3,4,5.
Mechanism of action
As described in the research literature
As described in the research literature, the 23-membered cyclic analogues showed about 100-fold higher melanotropic potency than alpha-MSH in the lizard skin bioassay, with prolonged activity; increasing or decreasing the ring size reduced potency1.
In mice, MTII inhibited feeding in fasted C57BL/6J, ob/ob and agouti A(Y) mice and in mice given neuropeptide Y, and this inhibition was blocked by the melanocortin antagonist SHU9119. The authors concluded that melanocortinergic neurons exert a tonic inhibition of feeding2. A comparison of melanocortin ligands on cloned rat MC3 and MC4 receptors related their in vitro potencies to melanocortin-induced grooming, which was attributed to the MC4 receptor3.
Research areas
What published studies have examined
Central melanocortin system and feeding
Studies used MTII and the antagonist SHU9119 to test the role of hypothalamic melanocortin receptors in feeding and the agouti obesity syndrome2. In chow-fed and diet-induced obese rats, central MTII was examined for effects on caloric intake, body weight, visceral adiposity, oxygen consumption and brown adipose tissue UCP14. In rat pups, MTII was used to study hypothalamic c-Fos activation, food intake and UCP1 mRNA before feeding circuitry is fully developed5.
Receptor subtype pharmacology
Nine melanocortin ligands, including melanotan II and [Nle4, D-Phe7]-alpha-MSH, were characterised on cloned rat MC3 and MC4 receptors and in a rat grooming model3.
Sources [3]
Development history
A review by the originating group traces the design of melanotan I and melanotan II, their progression into clinical investigation and the derivation of the later analogue PT-141 from melanotan II6.
Sources [6]
Specifications
- Sequence
- Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 (lactam bridge between Asp and Lys)
- Molecular formula
- C50H69N15O9
- Molecular weight
- 1024.2 g/mol
- CAS number
- 121062-08-6
Vial
- Form
- White to off-white lyophilised powder in a sealed vial (10 mg)
- Storage
- Store lyophilised powder at -20 °C, protected from light and moisture. Once reconstituted, keep refrigerated at 2 to 8 °C and protect from light.
- Solubility and reconstitution
- Reconstitute with bacteriostatic water. Add the diluent slowly down the inside wall of the vial and swirl gently until clear; do not shake.
Mist Applicator
- Form
- 10 mg in a vial fitted with a 10 mL mist applicator
- Storage
- Store as directed on the product label, protected from light.
- Solubility and reconstitution
- Prepare and use as directed on the product label.
References
- 1
Potent and prolonged acting cyclic lactam analogues of alpha-melanotropin: design based on molecular dynamics.
Al-Obeidi F, Castrucci AM, Hadley ME, et al. Journal of Medicinal Chemistry, 1989.
- 2
Role of melanocortinergic neurons in feeding and the agouti obesity syndrome.
Fan W, Boston BA, Kesterson RA, et al. Nature, 1997.
- 3
Characterization of melanocortin receptor ligands on cloned brain melanocortin receptors and on grooming behavior in the rat.
Adan RA, Szklarczyk AW, Oosterom J, et al. European Journal of Pharmacology, 1999.
- 4
Unabated anorexic and enhanced thermogenic responses to melanotan II in diet-induced obese rats despite reduced melanocortin 3 and 4 receptor expression.
Li G, Zhang Y, Wilsey JT, et al. The Journal of Endocrinology, 2004.
- 5
Melanocortinergic activation by melanotan II inhibits feeding and increases uncoupling protein 1 messenger ribonucleic acid in the developing rat.
Glavas MM, Joachim SE, Draper SJ, et al. Endocrinology, 2007.
- 6
Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization.
Hadley ME, Dorr RT Peptides, 2006.
This page is provided for research and educational reference only. It does not constitute medical advice, dosing guidance, or a recommendation for use. All compounds are strictly for laboratory and in-vitro research purposes.