WAY-181187 (SAX187) is a novel, potent and selective 5-HT6 receptor agonist with a Ki of 2.2 nM and an EC50 of 6.6 nM. WAY-181187 exhibits a full receptor agonist profile (WAY-EC50=6.6 nM, Emax=93%) and a high affinity binding (2.2 and 4.8 nM, respectively) at the human 5-HT6 receptor. Without affecting glutamate or norepinephrine levels, acute subcutaneous (s.c.) administration of WAY-181187 (3–30 mg/kg) markedly raised extracellular GABA concentrations in the rat frontal cortex.

Physicochemical Properties

Molecular Formula	C15H13CLN4O2S2
Molecular Weight	380.87232
Exact Mass	380.017
CAS #	554403-49-5
Related CAS #	WAY-181187 oxalate; 1883548-85-3; WAY-181187 hydrochloride; 554403-08-6
PubChem CID	10150497
Appearance	White to yellow solid powder
LogP	4.523
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	4
Heavy Atom Count	24
Complexity	572
Defined Atom Stereocenter Count	0
InChi Key	RYBOXBBYCVOYNO-UHFFFAOYSA-N
InChi Code	InChI=1S/C15H13ClN4O2S2/c16-13-14(19-7-8-23-15(19)18-13)24(21,22)20-9-10(5-6-17)11-3-1-2-4-12(11)20/h1-4,7-9H,5-6,17H2
Chemical Name	2-[1-(6-chloroimidazo[2,1-b][1,3]thiazol-5-yl)sulfonylindol-3-yl]ethanamine
Synonyms	WAY-181187; WAY 181187; WAY181187; SAX187; SAX-187; SAX187
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	5-HT6 Receptor ( Ki = 2.2 nM ); 5-HT6 Receptor ( EC50 = 6.6 nM )
ln Vitro	WAY-181187 (1 and 10 μM) enhances ERK1/2 activation. WAY-181187 wood increases Fyn Manhattan activity[2]. Western Blot Analysis[2] Cell line: HEK/HA-5-HT6 receptor cell concentration: 1 and 10 μM Incubation time: 5 minutes of pretreatment Results: The activation of ERK1/2 increased at both 1 and 10 μM concentrations.
ln Vivo	Acute administration of WAY-181187 (3-30 mg/kg, sc) significantly increased extracellular GABA concentrations without altering glutamate or nordepine levels in the FX frontal lobes. Additionally, WAY-181187 (30 mg/kg, sc) modulates but significantly reduces cortical dopamine and 5-HT levels [1]. Animal model: Adult male Sprague-Dawley rat, body weight 280–350 g[1] Dosage: 3, 10 or 30 mg/kg Administration: Acute subcutaneous administration Results: Significant increase in extracellular GABA concentration without alteration Levels of glutamate or norepinephrine.
Cell Assay	Cell Line: HEK/HA-5-HT6 receptor cells Concentration: 1 and 10 μM Incubation Time: Pretreatment 5 minutes Result: Increased activation of ERK1/2 both at 1 and 10 μM concentrations.
Animal Protocol	Adult male Sprague-Dawley rats weighing 280–350 g 3, 10, or 30 mg/kg Acute dministered by s.c.
References	[1]. Neuropharmacological Profile of Novel and Selective 5-HT6 Receptor Agonists: WAY-181187 and WAY-208466. Neuropsychopharmacology. 2008 May;33(6):1323-35. [2]. ST1936 Stimulates cAMP, Ca2+, ERK1/2 and Fyn Kinase Through a Full Activation of Cloned Human 5-HT6 Receptors. Eur J Pharmacol. 2011 Jul 1;661(1-3):8-14.

Solubility Data

Solubility (In Vitro)

DMSO: ~100 mg/mL (~262.6 mM）

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.56 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (6.56 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.56 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6256 mL	13.1278 mL	26.2557 mL
	5 mM	0.5251 mL	2.6256 mL	5.2511 mL
	10 mM	0.2626 mL	1.3128 mL	2.6256 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.