setmelanotide   Click here for help

GtoPdb Ligand ID: 9272

Synonyms: BIM-22493 | Imcivree® | IRC-022493 | RM-493
Approved drug
setmelanotide is an approved drug (FDA (2020))
Comment: Setmelanotide is an agonist of melanocortin receptors, with approximately 20-fold selectivity for the melanocortin 4 receptor subtype [5]. Chemically it is an eight-amino-acid cyclic peptide, that is able to cross the blood-brain barrier when administered peripherally. Setmelanotide offers anti-obesity potential.

HELM annotation : PEPTIDE1{[ac].R.C.[dA].H.[dF].R.W.C.[am]}$PEPTIDE1,PEPTIDE1,3:R3-9:R3$$$
INN record documents the sequence as N2-acetyl-L-arginyl-L-cysteinyl-D-alanyl-L-histidyl-D-phenylalanyl-L-arginyl-L-tryptophyl-L-cysteinamide, cyclic (2-8)-disulfide.
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2D Structure
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SMILES / InChI / InChIKey
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Canonical SMILES NC(=NCCCC(C(=O)NC1CSSCC(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C(NC1=O)C)Cc1[nH]cnc1)Cc1ccccc1)CCCN=C(N)N)Cc1c[nH]c2c1cccc2)C(=O)N)NC(=O)C)N
Isomeric SMILES NC(=NCCC[C@@H](C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](NC(=O)[C@@H](NC(=O)[C@H](NC1=O)C)Cc1[nH]cnc1)Cc1ccccc1)CCCN=C(N)N)Cc1c[nH]c2c1cccc2)C(=O)N)NC(=O)C)N
InChI InChI=1S/C49H68N18O9S2/c1-26-41(70)63-37(20-30-22-55-25-59-30)46(75)64-35(18-28-10-4-3-5-11-28)44(73)62-34(15-9-17-57-49(53)54)43(72)65-36(19-29-21-58-32-13-7-6-12-31(29)32)45(74)66-38(40(50)69)23-77-78-24-39(47(76)60-26)67-42(71)33(61-27(2)68)14-8-16-56-48(51)52/h3-7,10-13,21-22,25-26,33-39,58H,8-9,14-20,23-24H2,1-2H3,(H2,50,69)(H,55,59)(H,60,76)(H,61,68)(H,62,73)(H,63,70)(H,64,75)(H,65,72)(H,66,74)(H,67,71)(H4,51,52,56)(H4,53,54,57)/t26-,33+,34+,35-,36+,37+,38+,39+/m1/s1
InChI Key HDHDTKMUACZDAA-PHNIDTBTSA-N
References
1. Chen KY, Muniyappa R, Abel BS, Mullins KP, Staker P, Brychta RJ, Zhao X, Ring M, Psota TL, Cone RD et al.. (2015)
RM-493, a melanocortin-4 receptor (MC4R) agonist, increases resting energy expenditure in obese individuals.
J Clin Endocrinol Metab, 100 (4): 1639-45. [PMID:25675384]
2. Clément K, van den Akker E, Argente J, Bahm A, Chung WK, Connors H, De Waele K, Farooqi IS, Gonneau-Lejeune J, Gordon G et al.. (2020)
Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials.
Lancet Diabetes Endocrinol, 8 (12): 960-970. [PMID:33137293]
3. Fani L, Bak S, Delhanty P, van Rossum EF, van den Akker EL. (2014)
The melanocortin-4 receptor as target for obesity treatment: a systematic review of emerging pharmacological therapeutic options.
Int J Obes (Lond.), 38 (2): 163-9. [PMID:23774329]
4. Farooqi IS, O'Rahilly S. (2008)
Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity.
Nat Clin Pract Endocrinol Metab, 4 (10): 569-77. [PMID:18779842]
5. Kumar KG, Sutton GM, Dong JZ, Roubert P, Plas P, Halem HA, Culler MD, Yang H, Dixit VD, Butler AA. (2009)
Analysis of the therapeutic functions of novel melanocortin receptor agonists in MC3R- and MC4R-deficient C57BL/6J mice.
Peptides, 30 (10): 1892-900. [PMID:19646498]
6. Kühnen P, Clément K, Wiegand S, Blankenstein O, Gottesdiener K, Martini LL, Mai K, Blume-Peytavi U, Grüters A, Krude H. (2016)
Proopiomelanocortin Deficiency Treated with a Melanocortin-4 Receptor Agonist.
N Engl J Med, 375 (3): 240-6. [PMID:27468060]