IS-159

IS-159, also known as serotonin-O-carboxymethylglycyltyrosinamide, is a triptan-like serotonin 5-HT_1B and 5-HT_1D receptor agonist which was under development for the treatment of migraine but was never marketed.^{[1][2][3][6][5][7]} It is taken intranasally or subcutaneously.^[1][2][3]

Other namesIS159; Serotonin-O-carboxymethylglycyltyrosinamide; Serotonin-carboxylmethyleneoxy-L-tyrosylglycinamide; 2-(3-(2-aminoethyl)-1H-indol-5-yloxy)acetyl-L-tyrosyl-glycinamide

Routes of
administrationIntranasal, subcutaneous^[1][2][3]

Drug classSerotonin 5-HT_1B and 5-HT_1D receptor agonist; Triptan-like drug; Antimigraine agent

ATC code

• None

Quick facts Clinical data, Other names ...

IS-159

Clinical data
Other names	IS159; Serotonin-O-carboxymethylglycyltyrosinamide; Serotonin-carboxylmethyleneoxy-L-tyrosylglycinamide; 2-(3-(2-aminoethyl)-1H-indol-5-yloxy)acetyl-L-tyrosyl-glycinamide
Routes of administration	Intranasal, subcutaneous[1][2][3]
Drug class	Serotonin 5-HT1B and 5-HT1D receptor agonist; Triptan-like drug; Antimigraine agent
ATC code	None
Pharmacokinetic data
Onset of action	15–20 minutes (TmaxTooltip time to peak levels)[2][4]
Elimination half-life	2–2.5 hours[2][4][5]
Identifiers
IUPAC name (2S)-2-[[2-[[3-(2-aminoethyl)-1H-indol-5-yl]oxy]acetyl]amino]-N-(2-amino-2-oxoethyl)-3-(4-hydroxyphenyl)propanamide
CAS Number	133790-13-3
PubChem CID	196859
ChemSpider	170507
UNII	7N2D7W2TCJ
CompTox Dashboard (EPA)	DTXSID80928273
Chemical and physical data
Formula	C23H27N5O5
Molar mass	453.499 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1=CC(=CC=C1C[C@@H](C(=O)NCC(=O)N)NC(=O)COC2=CC3=C(C=C2)NC=C3CCN)O
InChI 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

Close

The drug is a small serotonin-containing peptide and is described as being peripherally selective.^[3] It acts as a selective and potent serotonin 5-HT_1B and 5-HT_1D receptor agonist (K_i = 3.2 nM and 1.6 nM, respectively).^[8][4] IS-159 has more than 300-fold lower affinity for the serotonin 5-HT_1A receptor (K_i = 1,000) and is inactive at the serotonin 5-HT_1E and 5-HT_1F receptors (K_i = >10,000 nM).^[8][9][10] The drug's pharmacokinetics in humans have been studied.^[2][4][5]

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.^[1][2] The drug reached phase 2 clinical trials prior to the discontinuation of its development.^[1][2][5]