Novo Nordisk 

Compound Sharing

Novo Nordisk 

Compound Sharing


Long-acting a-MSH analogue

Amount per vial
1000 nmol

Alpha- melanocyte-stimulating hormone (a-MSH) is one of the native ligands for the melanocortin receptors 1-5. The melanocortin 4 receptor (MC4-R) is involved in the regulation of food intake and body weight. 

NNC0070-0453 is a long-acting MC4-R selective a-MSH analogue which is N-terminally modified with a long chain fatty acid derivative.


Selected calculated properties for NNC0070-0453 and MT-II (NNC0090-1735) are listed in the table.
PropertyNNC0070-0453MT-II (NNC0090-1735)
MW (Da)20921024
pI (calculated)5.813.0
Fatty acidC16-tetrazole-
Sum formulaC96 H146 N28 O25C50 H69 N15 O9
Extinction coefficient (calculated, 280 nm)55005500

2D sketch of NNC0070-0453. The salt bridge in a-MSH between Glu5 and Lys11 is replaced with a lactam bridge. Gly-10 has been removed and the oxidative labile Met4 has been replaced with an isosteric norleucine (Nor). A fatty acid derivative (C16-tetrazole) is attached to the N-terminal.
2D sketch of the structure of MT-II (NNC0090-1735), a widely used reference for a-MSH used in the litterature.

New receptor binding data from scintillation proximity assays (SPA) binding assays (different from the previously published data) are listed in the table.
ReceptorNNC0070-0453 (IC50, nM)MT-II (IC50, nM)NDP-a-MSH (IC50, nM)
hMC1R, hMC3R, hMC4R, hMC5R: human melanocortin receptor subtype 1,3,4, and 5, respectively.

For NNC0070-0453 the mean T1/2 in Sprague Dawley rats were 28 h after subcutaneous (s.c.) dosing. NNC0070-0453 and other long chain fatty acid analogues have an effect up to 48 h in an acute feeding study in male Sprague-Dawley rats after a single s.c. administration (see the Conde-Frieboes K et al., 2012, reference listed in the reference section further details).

The reference compound is MT-II (NNC0090-1735), which is a short cyclic analogue of a-MSH. Please indicate in the 'Purpose' field when you order NNC0070-0453 if you would like to have MT-II (NNC0090-1735) included in your shipment.

For in vitro experiments the compound can be dissolved in DMSO, 80/20% DMSO/MilliQ water or low salt buffer with neutral to basic pH. Peptides and proteins have a tendency to adhere to glass and plastic surfaces. This may at low concentration impact the actual amount in solution. To minimize this unspecific adherence, adding detergents or inert proteins like e.g., ovalbumin or other serum albumins to the solution can minimize this phenomenon. In case albumins are added to peptide/protein solutions, ensure that the albumins are free of any proteases, but be aware that it will affect the apparent potency and affinity in in vitro assays in case a fatty acid is attached to the compound.

Conde-Frieboes K et al.
Identification and in vivo and in vitro characterization of Long Acting and Melanocortin 4 Receptor (MC4-R) selective a-melanocyte-stimulating hormone (a-MSH) analogues
J Med Chem. 2012;55(5):1969-77
Royalty JE et al.
Investigation of safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses of a long-acting a-MSH analogue in healthy overweight and obese subjects
J Clin Pharmacol. 2014; 54(4): 394–404.
al-Obeidi F et al.
Design of a new class of superpotent cyclic a-melanotropins based on quenched dynamic simulations
J. Am. Chem. Soc. 1989, 111, 3413– 3416