IS-159

IS-159
Clinical data
Other namesIS159; Serotonin-O-carboxymethylglycyltyrosinamide; Serotonin-carboxylmethyleneoxy-L-tyrosylglycinamide; 2-(3-(2-aminoethyl)-1H-indol-5-yloxy)acetyl-L-tyrosyl-glycinamide
Routes of
administration		Intranasal, subcutaneous
Drug classSerotonin 5-HT1B and 5-HT1D receptor agonist; Triptan-like drug; Antimigraine agent
ATC code
  • None
Pharmacokinetic data
Onset of action15–20 minutes (TmaxTooltip time to peak levels)
Elimination half-life2–2.5 hours
Identifiers
  • (2S)-2-[[2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]acetyl]amino]-N-(2-amino-2-oxoethyl)-3-(4-hydroxyphenyl)propanamide
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC23H27N5O5
Molar mass453.499 g·mol−1
3D model (JSmol)
  • C1=CC(=CC=C1C[C@@H](C(=O)NCC(=O)N)NC(=O)COC2=CC3=C(C=C2)NC=C3CCN)O
  • InChI=1S/C23H27N5O5/c24-8-7-15-11-26-19-6-5-17(10-18(15)19)33-13-22(31)28-20(23(32)27-12-21(25)30)9-14-1-3-16(29)4-2-14/h1-6,10-11,20,26,29H,7-9,12-13,24H2,(H2,25,30)(H,27,32)(H,28,31)/t20-/m0/s1
  • Key:PBRWGFLPYQYNGI-FQEVSTJZSA-N

IS-159, also known as serotonin-O-carboxymethylglycyltyrosinamide, is a triptan-like serotonin 5-HT1B and 5-HT1D receptor agonist which was under development for the treatment of migraine but was never marketed. It is taken intranasally or subcutaneously.

The drug is a small serotonin-containing peptide and is described as being peripherally selective. It acts as a selective and potent serotonin 5-HT1B and 5-HT1D receptor agonist (Ki = 3.2 nM and 1.6 nM, respectively). IS-159 has more than 300-fold lower affinity for the serotonin 5-HT1A receptor (Ki = 1,000) and is inactive at the serotonin 5-HT1E and 5-HT1F receptors (Ki = >10,000 nM). The drug's pharmacokinetics in humans have been studied.

IS-159 was originated by Immunotech in France and was under development by Immunotech and The Medicines Company in the 1990s and early 2000s, but development was discontinued in 2003. The drug reached phase 2 clinical trials prior to the discontinuation of its development.

See also

References

  1. 1 2 3 4 5 "IS 159". AdisInsight. 17 January 2020. Retrieved 25 January 2026.
  2. 1 2 3 4 5 6 7 8 "IS 159". Drugs in R&D. 2 (6): 390–391. December 1999. doi:10.2165/00126839-199902060-00006. PMID 10763448.
  3. 1 2 3 4 Mucke H (December 2002). "Therapies in development for the treatment of migraine". Expert Opinion on Investigational Drugs. 11 (12): 1813–1820. doi:10.1517/13543784.11.12.1813. PMID 12457440.
  4. 1 2 3 4 Ramadan NM (2001). "Acute treatments: future developments". Current Medical Research and Opinion. 17 Suppl 1: s81–s86. doi:10.1185/0300799039117018. PMID 12463284.
  5. 1 2 3 4 Dingemanse J, Soubrouillard C, Paris J, Pisano P, Blin O (August 2000). "Pronounced effect of caprylocaproyl macrogolglycerides on nasal absorption of IS-159, a peptide serotonin 1B/1D-receptor agonist". Clinical Pharmacology and Therapeutics. 68 (2): 114–121. doi:10.1067/mcp.2000.108196. PMID 10976542.
  6. ↑ Ramadan NM, Buchanan TM, Pearlman SH (2004). "Clinical Science: Peripheral and Central Trigeminal Targets for Acute Migraine Therapy: Early Clinical Trial Results". Headache Currents. 1 (1): 7–12. doi:10.1111/j.1743-5013.2004.10104.x. ISSN 1743-5005. Retrieved 25 January 2026.
  7. ↑ Chauveau J, Delaage MA (1997). "IS-159: A High-Affinity Specific 5-HT1D Full Receptor Agonist, Effective in the Acute Treatment of Migraine". Frontiers in Headache Research. 6th International Headache Research Seminar; 1995 Nov 17-19. 6. Copenhagen: 287–292.
  8. 1 2 Martin GR (1997). "Serotonin Receptor Involvement in the Pathogenesis and Treatment of Migraine". In Goadsby VG, Silberstein SD (eds.). Blue Books of Practical Neurology. Vol. 17. pp. 25–38. ISBN 978-0-7506-9871-9.
  9. ↑ Waeber C (November 2003). "Emerging drugs in migraine treatment". Expert Opinion on Emerging Drugs. 8 (2): 437–456. doi:10.1517/14728214.8.2.437. PMID 14661998.
  10. ↑ van den Broek RW (13 March 2002). Vascular Effects of Antimigraine Drugs: pharmacology of human in vitro models in migraine. RePub, Erasmus University Repository (Doctoral thesis). Erasmus University Rotterdam. Retrieved 25 January 2026.