Nemifitide

Nemifitide
Nemifitide
Systematic (IUPAC) name
(4R)-4-hydroxy-L-prolyl-N5-(diaminomethylidene)-L-ornithylglycyl-N-[(2S)-2-amino-3-(4-fluorophenyl)propanoyl]-L-tryptophanamide
Clinical data
Pregnancy cat.  ?
Legal status Non-regulated
Routes Subcutaneous injection
Pharmacokinetic data
Half-life 15-30 minutes[1]
Identifiers
CAS number 173240-15-8
ATC code None
PubChem CID 177265
ChemSpider 154356
UNII RO19OXA9NG YesY
Chemical data
Formula C33H43FN10O6 
Mol. mass 694.756 g/mol
SMILES eMolecules & PubChem

Nemifitide (INN-00835), also known as 4-F-Phe-4-OH-Pro-Arg-Gly-Trp-NH2, is a novel antidepressant drug with a pentapeptide structure similar to that of melanocyte-inhibiting factor (MIF-1).[1][2] It is under development by Tetragenex (previously Innapharma, Inc.) for the treatment of major depressive disorder.[3] It has been given to over 430 humans over the course of 12 clinical trials throughout a little over the past decade, and has reached Phase III studies, but has not yet been approved for marketing in any country.[3]

Nemifitide has shown mixed efficacy in alleviating depressive symptoms,[4][5] but in the cases in which it has worked, it has proven to have a rapid onset of action (~5-7 days), few to no side effects, and an excellent safety profile.[5] However, it is inactive orally, and must be administered via subcutaneous injection (SC). Remarkably, despite having a very short half-life of only 15-30 minutes,[1] in most or all studies assessing its efficacy, it has been administered merely once daily via the SC route, and yet is as effective as it is against depression.

Its mechanism of action is unclear, but since MIF-1 has been demonstrated to have similar antidepressant effects,[6] it may act in an analogous manner.[1][2] Of interest, however, is that nemifitide binds to several receptors at micromolar concentrations, including 5-HT2A, NPY1, bombesin, and melanocortin MC4 and MC5.[5] In addition, it has been determined to act in an antagonistic manner at the 5-HT2A receptor.[5] However, it is unclear whether any of these relatively weak actions are of significance.

See also

References

  1. ^ a b c d William O. Foye; Thomas L. Lemke; David A. Williams (1 September 2007). = R0W1ErpsQpkC&pg = PA596 Foye's principles of medicinal chemistry. Lippincott Williams & Wilkins. p. 596. ISBN 9780781768795. http://books.google.com/books?id = R0W1ErpsQpkC&pg = PA596. Retrieved 13 June 2011. 
  2. ^ a b Holtzheimer, PE; Nemeroff, CB (2008). "Novel targets for antidepressant therapies.". Current psychiatry reports 10 (6): 465–73. PMID 18980729. 
  3. ^ a b "Tetragenex Pharmaceuticals Inc. - Product Technology - Nemifitide". http://www.tetragenex.com/technology.html#nem. Retrieved 2011-06-13. 
  4. ^ Rakofsky, Jeffrey J; Holtzheimer, Paul E; Nemeroff, Charles B (2009). "Emerging targets for antidepressant therapies". Current Opinion in Chemical Biology 13 (3): 291–302. doi:10.1016/j.cbpa.2009.04.617. PMID 19501541. 
  5. ^ a b c d Renato D. Alarcón (2004). Antidepressants: past, present, and future. Springer. p. 575. ISBN 9783540430544. http://books.google.com/books?id=sO_hArhCxwMC&pg=PA575. 
  6. ^ Van Der Velde, CD (1983). "Rapid clinical effectiveness of MIF-I in the treatment of major depressive illness". Peptides 4 (3): 297–300. doi:10.1016/0196-9781(83)90136-5. PMID 6138756. 

Further reading

  • Dingemanse, J. (Jul 2003). "Nemifitide. Innapharma.". Curr Opin Investig Drugs 4 (7): 859–62. PMID 14619408. 



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  • Melanocyte-inhibiting factor — Systematic (IUPAC) name (S) N ((S) 1 (2 amino 2 oxoethylamino) 4 methyl 1 oxopentan 2 yl)pyrrolidine 2 carboxamide Clinical data MedlineP …   Wikipedia

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