Modimelanotide

Modimelanotide (INN) (code names AP-214, ABT-719, ZP-1480) is a melanocortinergic peptide drug derived from α-melanocyte-stimulating hormone (α-MSH) which was under development by, at different times, Action Pharma, Abbott Laboratories, AbbVie, and Zealand for the treatment of acute kidney injury.[1][2] It acts as a non-selective melanocortin receptor agonist, with IC50 values of 2.9 nM, 1.9 nM, 3.7 nM, and 110 nM at the MC1, MC3, MC4, and MC5 receptors.[3] Modimelanotide failed clinical trials for acute kidney injury despite showing efficacy in animal models,[4][5] and development was not further pursued.[1][2]

Modimelanotide
Clinical data
Other namesAcetylhexa-L-lysyl-α-MSH
ATC code
  • None
Identifiers
IUPAC name
  • N2-acetyl-L-lysyl-L-lysyl-L-lysyl-L-lysyl-L-lysyl-L-lysyl-L-seryl-L-tyrosyl-L-seryl-L-methionyl-L-alpha-glutamyl-L-histidyl-L-phenylalanyl-L-arginyl-L-tryptophylglycyl-L-lysyl-L-prolyl-L-valinamide
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC113H181N33O25S
Molar mass2433.96 g·mol−1
3D model (JSmol)
SMILES
  • [H]/N=C(\N)/NCCC[C@@H](C(=O)N[C@@H](Cc1c[nH]c2c1cccc2)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N3CCC[C@H]3C(=O)N[C@@H](C(C)C)C(=O)N)NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@H](Cc5c[nH]cn5)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@H](Cc6ccc(cc6)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)C
InChI
  • InChI=1S/C113H181N33O25S/c1-66(2)94(95(121)154)145-111(170)91-38-25-54-146(91)112(171)84(36-16-23-52-120)130-92(151)62-127-96(155)87(58-70-60-126-74-29-9-8-28-73(70)74)141-102(161)81(37-24-53-125-113(122)123)136-106(165)85(56-68-26-6-5-7-27-68)139-108(167)88(59-71-61-124-65-128-71)142-104(163)82(43-44-93(152)153)137-105(164)83(45-55-172-4)138-109(168)89(63-147)144-107(166)86(57-69-39-41-72(150)42-40-69)140-110(169)90(64-148)143-103(162)80(35-15-22-51-119)135-101(160)79(34-14-21-50-118)134-100(159)78(33-13-20-49-117)133-99(158)77(32-12-19-48-116)132-98(157)76(31-11-18-47-115)131-97(156)75(129-67(3)149)30-10-17-46-114/h5-9,26-29,39-42,60-61,65-66,75-91,94,126,147-148,150H,10-25,30-38,43-59,62-64,114-120H2,1-4H3,(H2,121,154)(H,124,128)(H,127,155)(H,129,149)(H,130,151)(H,131,156)(H,132,157)(H,133,158)(H,134,159)(H,135,160)(H,136,165)(H,137,164)(H,138,168)(H,139,167)(H,140,169)(H,141,161)(H,142,163)(H,143,162)(H,144,166)(H,145,170)(H,152,153)(H4,122,123,125)/t75-,76-,77-,78-,79-,80-,81-,82-,83-,84-,85-,86-,87-,88-,89-,90-,91-,94-/m0/s1
  • Key:WHRVKPBBRZHWTN-ZHHKRVSMSA-N

See also

References
  1. Ramos AM, González-Guerrero C, Sanz A, Sanchez-Niño MD, Rodríguez-Osorio L, Martín-Cleary C, et al. (May 2015). "Designing drugs that combat kidney damage". Expert Opinion on Drug Discovery. 10 (5): 541–56. doi:10.1517/17460441.2015.1033394. PMID 25840605. S2CID 24191324.
  2. Montero-Melendez T (May 2015). "ACTH: The forgotten therapy". Seminars in Immunology. 27 (3): 216–26. doi:10.1016/j.smim.2015.02.003. PMID 25726511.
  3. "Renal-Urologic drugs". Drug Data Reports. Prous Science. 29 (1): 42. 2007. ISSN 0379-4121.
  4. Doi K, Hu X, Yuen PS, Leelahavanichkul A, Yasuda H, Kim SM, et al. (June 2008). "AP214, an analogue of alpha-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality". Kidney International. 73 (11): 1266–74. doi:10.1038/ki.2008.97. PMC 2398767. PMID 18354376.
  5. Simmons MN, Subramanian V, Crouzet S, Haber GP, Colombo JR, Ukimura O, et al. (April 2010). "Alpha-melanocyte stimulating hormone analogue AP214 protects against ischemia induced acute kidney injury in a porcine surgical model". The Journal of Urology. 183 (4): 1625–9. doi:10.1016/j.juro.2009.12.007. PMID 20172543.
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