SPS-4251 [PAP-1; SPS4251; 5-(4-Phenoxybutoxy)psoralen] is a novel and potent KCNA3 channel blocker (inhibitor of Kv1.3, voltage-gated K+ channel) with the potential to be used in treatment of multiple sclerosis.

Physicochemical Properties

Molecular Formula	C21H18O5
Molecular Weight	350.37
Exact Mass	350.115
CAS #	870653-45-5
PubChem CID	11302540
Appearance	White to yellow solid powder
Density	1.3±0.1 g/cm3
Boiling Point	555.8±50.0 °C at 760 mmHg
Flash Point	289.9±30.1 °C
Vapour Pressure	0.0±1.5 mmHg at 25°C
Index of Refraction	1.619
LogP	4.56
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	7
Heavy Atom Count	26
Complexity	499
Defined Atom Stereocenter Count	0
InChi Key	KINMYBBFQRSVLL-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H18O5/c22-20-9-8-16-19(26-20)14-18-17(10-13-24-18)21(16)25-12-5-4-11-23-15-6-2-1-3-7-15/h1-3,6-10,13-14H,4-5,11-12H2
Chemical Name	4-(4-phenoxybutoxy)furo[3,2-g]chromen-7-one
Synonyms	SPS4251 SPS 4251 SPS-4251PAP-1SPS42515-(4-Phenoxybutoxy)psoralen
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

ln Vitro	PAP-1 (2-100 nM; 30 minutes) suppresses CCR7-TEM cell proliferation with an IC50 of 10 nM [1].
ln Vivo	Lewis rats treated intraperitoneally with PAP-1 (0.3–3 mg/kg) three times a day for 48 hours are protected against delayed-type hypersensitivity (DTH) [1].
Cell Assay	Cell proliferation assay [1] Cell Types: CCR7-TEM cells (anti-CD3 Ab stimulation) Tested Concentrations: 2, 10, 25, 100 nM Incubation Duration: 30 minutes Experimental Results: Inhibits the proliferation of CCR7-TEM cells, IC50 is 10 nM.
Animal Protocol	Animal/Disease Models: 9 to 11 weeks old female Lewis rats [1] Usage and Doses: intraperitoneal (ip) injection; 3 times a day for 48 hrs (hrs (hours)). Dosing: 0.3, 1, 3 mg/kg. Experimental Results: Dose-dependent inhibition of DTH response.
References	[1]. Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases. Mol Pharmacol. 2005 Nov;68(5):1254-70. [2]. Pharmacokinetics, toxicity, and functional studies of the selective Kv1.3 channel blocker 5-(4-phenoxybutoxy)psoralen in rhesus macaques. Exp Biol Med (Maywood). 2007 Nov;232(10):1338-54.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~142.71 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.14 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 (7.14 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 (7.14 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	2.8541 mL	14.2706 mL	28.5413 mL
	5 mM	0.5708 mL	2.8541 mL	5.7083 mL
	10 mM	0.2854 mL	1.4271 mL	2.8541 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.