afamelanotide   

GtoPdb Ligand ID: 1324

Synonyms: α-NDP-MSH | [Nle4,dPhe7]α-MSH | CUV-1647 | CUV1647 | NDP-MSH | Scenesse®
afamelanotide is an approved drug (EMA (2014), FDA (2019))
Comment: Afamelanotide is a synthetic analogue of α-MSH, and is a first-in-class clinically used melanocortin-1 receptor agonist. It is used for certain dematological applications [5-6].
2D Structure
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SMILES / InChI / InChIKey
Canonical SMILES CCCCC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NCC(=O)NC(C(=O)N1CCCC1C(=O)NC(C(=O)N)C(C)C)CCCCN)Cc1c[nH]c2c1cccc2)CCCNC(=N)N)Cc1ccccc1)Cc1[nH]cnc1)CCC(=O)O)NC(=O)C(NC(=O)C(NC(=O)C(NC(=O)C)CO)Cc1ccc(cc1)O)CO
Isomeric SMILES CCCC[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N)C(C)C)CCCCN)Cc1c[nH]c2c1cccc2)CCCNC(=N)N)Cc1ccccc1)Cc1[nH]cnc1)CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)C)CO)Cc1ccc(cc1)O)CO
InChI InChI=1S/C78H111N21O19/c1-5-6-19-52(91-75(116)61(41-101)97-72(113)57(34-46-24-26-49(103)27-25-46)94-74(115)60(40-100)88-44(4)102)68(109)92-54(28-29-64(105)106)70(111)96-59(36-48-38-83-42-87-48)73(114)93-56(33-45-16-8-7-9-17-45)71(112)90-53(22-14-31-84-78(81)82)69(110)95-58(35-47-37-85-51-20-11-10-18-50(47)51)67(108)86-39-63(104)89-55(21-12-13-30-79)77(118)99-32-15-23-62(99)76(117)98-65(43(2)3)66(80)107/h7-11,16-18,20,24-27,37-38,42-43,52-62,65,85,100-101,103H,5-6,12-15,19,21-23,28-36,39-41,79H2,1-4H3,(H2,80,107)(H,83,87)(H,86,108)(H,88,102)(H,89,104)(H,90,112)(H,91,116)(H,92,109)(H,93,114)(H,94,115)(H,95,110)(H,96,111)(H,97,113)(H,98,117)(H,105,106)(H4,81,82,84)/t52-,53-,54-,55-,56+,57-,58-,59-,60-,61-,62-,65-/m0/s1
InChI Key UAHFGYDRQSXQEB-LEBBXHLNSA-N
References
1. Adan RA, Szklarczyk AW, Oosterom J, Brakkee JH, Nijenhuis WA, Schaaper WM, Meloen RH, Gispen WH. (1999)
Characterization of melanocortin receptor ligands on cloned brain melanocortin receptors and on grooming behavior in the rat.
Eur J Pharmacol, 378: 249-258. [PMID:10493100]
2. Kim ES, Garnock-Jones KP. (2016)
Afamelanotide: A Review in Erythropoietic Protoporphyria.
Am J Clin Dermatol, 17 (2): 179-85. [PMID:26979527]
3. Luger TA, Böhm M. (2015)
An α-MSH analog in erythropoietic protoporphyria.
J. Invest. Dermatol., 135 (4): 929-931. [PMID:25785940]
4. MacNeil DJ, Howard AD, Guan X, Fong TM, Nargund RP, Bednarek MA, Goulet MT, Weinberg DH, Strack AM, Marsh DJ et al.. (2002)
The role of melanocortins in body weight regulation: opportunities for the treatment of obesity.
Eur. J. Pharmacol., 440 (2-3): 141-57. [PMID:12007532]
5. McNeil MM, Nahhas AF, Braunberger TL, Hamzavi IH. (2018)
Afamelanotide in the Treatment of Dermatologic Disease.
Skin Therapy Lett., 23 (6): 6-10. [PMID:30517779]
6. Minder EI, Barman-Aksoezen J, Schneider-Yin X. (2017)
Pharmacokinetics and Pharmacodynamics of Afamelanotide and its Clinical Use in Treating Dermatologic Disorders.
Clin Pharmacokinet, 56 (8): 815-823. [PMID:28063031]
7. Sawyer TK, Sanfilippo PJ, Hruby VJ, Engel MH, Heward CB, Burnett JB, Hadley ME. (1980)
4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity.
Proc. Natl. Acad. Sci. U.S.A., 77 (10): 5754-8. [PMID:6777774]
8. Smith AI, Funder JW. (1988)
Proopiomelanocortin processing in the pituitary, central nervous system, and peripheral tissues.
Endocr. Rev., 9: 159-179. [PMID:3286233]
9. Yang YK, Fong TM, Dickinson CJ, Mao C, Li JY, Tota MR, Mosley R, Van Der Ploeg LH, Gantz I. (2000)
Molecular determinants of ligand binding to the human melanocortin-4 receptor.
Biochemistry, 39 (48): 14900-11. [PMID:11101306]