SPS-4251 | AS-77 | PAP-1 | CAS#870653-45-5 | KCNA3 Channel Blocker

MedKoo Cat#: 527717 | Name: SPS-4251

Description:

WARNING: This product is for research use only, not for human or veterinary use.

SPS-4251, also known as PAP-1, is a KCNA3 (Potassium voltage-gated channel, shaker-related subfamily, member 3) channel blocker potentially for the treatment of plaque psoriasis. Kv1.3 channels regulate the activation/proliferation of effector memory T cells and thus play a critical role in the pathogenesis of autoimmune diseases. SPS-4251 reduced the secretion of TNFα by adipose tissue but had no effect on the secretion of IL-6. SPS-4251 can also potentially inhibit the exocytosis of cytoplasmic granules from CD4(+)CD28(null) T cells.

Chemical Structure

SPS-4251

CAS#870653-45-5

Theoretical Analysis

MedKoo Cat#: 527717

Name: SPS-4251

CAS#: 870653-45-5

Chemical Formula: C21H18O5

Exact Mass: 350.1154

Molecular Weight: 350.37

Elemental Analysis: C, 71.99; H, 5.18; O, 22.83

Price and Availability

Size	Price	Availability
25mg	USD 250.00	2 Weeks
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,650.00	2 Weeks
2g	USD 6,250.00	2 Weeks

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Synonym

SPS-4251; SPS 4251; SPS4251; AS-77; PAP-1; AS 77; PAP 1; AS77; PAP1

IUPAC/Chemical Name

4-(4-phenoxybutoxy)-7H-furo[3,2-g]chromen-7-one

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

SMILES Code

O=C1C=CC2=C(OCCCCOC3=CC=CC=C3)C4=C(OC=C4)C=C2O1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

SPS-4251 is an inhibitor of Kv1.3 voltage-gated potassium channels (EC50 = 2 nM at -80 mV in cells overexpressing the human channel). It is selective for Kv1.3 over a panel of 22 ion channels, including potassium, sodium, calcium, and chloride channels (EC50s = 45-15,000 nM for all).

In vitro activity:

SPS-4251 is a promising tool for immunosuppression, offering potential for oral immunomodulators. SPS-4251 had 2- to 50-fold selectivity for the lymphocyte K+ channel Kv1.3 over Kv1.5. SPS-4251 effectively blocks Kv1.3 without cytotoxic effects and inhibits TEM cell proliferation. Reference: Mol Pharmacol. 2005 Nov;68(5):1254-70. https://pubmed.ncbi.nlm.nih.gov/16099841/

In vivo activity:

In a mouse model of DSS-induced colitis, SPS-4251 reduced DSS-induced colonic pathological damage, DAI score, MPO activity and levels of IL-1, IL-6, TNF-a, IL-18. Compared with the DSS model group, the expression of Kv1.3, iNOS, NLRP3, ASC, caspase-1p20, pro-IL-1β and IL-1β in colon were decreased in the DSS-induced colitis mice with SPS-4251 injection. SPS-4251 also reduced the expression of Kv1.3, iNOS, NLRP3, caspase-1p20 and IL-1β on macrophages in colitis mice. Reference: Int Immunopharmacol. 2019 Oct;75:105776. https://pubmed.ncbi.nlm.nih.gov/31351364/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	9.0	25.69

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 350.37 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Li M, Zhang Y, Zeb A, Wu Y, Cheng L. Bergamottin and PAP-1 Induced ACE2 Degradation to Alleviate Infection of SARS-CoV-2. Int J Mol Sci. 2022 Oct 19;23(20):12565. doi: 10.3390/ijms232012565. PMID: 36293419; PMCID: PMC9604380. 2. Schmitz A, Sankaranarayanan A, Azam P, Schmidt-Lassen K, Homerick D, Hänsel W, Wulff H. 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. doi: 10.1124/mol.105.015669. Epub 2005 Aug 11. PMID: 16099841. 3. Mei Y, Fang C, Ding S, Liu X, Hu J, Xu J, Mei Q. PAP-1 ameliorates DSS-induced colitis with involvement of NLRP3 inflammasome pathway. Int Immunopharmacol. 2019 Oct;75:105776. doi: 10.1016/j.intimp.2019.105776. Epub 2019 Jul 24. PMID: 31351364. 4. Ngala RA, Zaibi MS, Langlands K, Stocker CJ, Arch JR, Cawthorne MA. Stimulation of glucose uptake in murine soleus muscle and adipocytes by 5-(4-phenoxybutoxy)psoralen (PAP-1) may be mediated by Kv1.5 rather than Kv1.3. PeerJ. 2014 Oct 7;2:e614. doi: 10.7717/peerj.614. PMID: 25320682; PMCID: PMC4193404.

In vitro protocol:

In vivo protocol:

1. Mei Y, Fang C, Ding S, Liu X, Hu J, Xu J, Mei Q. PAP-1 ameliorates DSS-induced colitis with involvement of NLRP3 inflammasome pathway. Int Immunopharmacol. 2019 Oct;75:105776. doi: 10.1016/j.intimp.2019.105776. Epub 2019 Jul 24. PMID: 31351364. 2. Ngala RA, Zaibi MS, Langlands K, Stocker CJ, Arch JR, Cawthorne MA. Stimulation of glucose uptake in murine soleus muscle and adipocytes by 5-(4-phenoxybutoxy)psoralen (PAP-1) may be mediated by Kv1.5 rather than Kv1.3. PeerJ. 2014 Oct 7;2:e614. doi: 10.7717/peerj.614. PMID: 25320682; PMCID: PMC4193404.

1: Kundu-Raychaudhuri S, Chen YJ, Wulff H, Raychaudhuri SP. Kv1.3 in psoriatic disease: PAP-1, a small molecule inhibitor of Kv1.3 is effective in the SCID mouse psoriasis--xenograft model. J Autoimmun. 2014 Dec;55:63-72. doi: 10.1016/j.jaut.2014.07.003. PubMed PMID: 25175978; PubMed Central PMCID: PMC4398058. 2: Ngala RA, Zaibi MS, Langlands K, Stocker CJ, Arch JR, Cawthorne MA. Stimulation of glucose uptake in murine soleus muscle and adipocytes by 5-(4-phenoxybutoxy)psoralen (PAP-1) may be mediated by Kv1.5 rather than Kv1.3. PeerJ. 2014 Oct 7;2:e614. doi: 10.7717/peerj.614. PubMed PMID: 25320682; PubMed Central PMCID: PMC4193404. 3: Wu X, Xu R, Cao M, Ruan L, Wang X, Zhang C. Effect of the Kv1.3 voltage-gated potassium channel blocker PAP-1 on the initiation and progress of atherosclerosis in a rat model. Heart Vessels. 2015 Jan;30(1):108-14. doi: 10.1007/s00380-013-0462-7. PubMed PMID: 24441938. 4: Cidad P, Novensà L, Garabito M, Batlle M, Dantas AP, Heras M, López-López JR, Pérez-García MT, Roqué M. K+ channels expression in hypertension after arterial injury, and effect of selective Kv1.3 blockade with PAP-1 on intimal hyperplasia formation. Cardiovasc Drugs Ther. 2014 Dec;28(6):501-11. doi: 10.1007/s10557-014-6554-5. Erratum in: Cardiovasc Drugs Ther. 2015 Apr;29(2):199-200. PubMed PMID: 25348824. 5: Jorgensen C, Darré L, Vanommeslaeghe K, Omoto K, Pryde D, Domene C. In silico identification of PAP-1 binding sites in the Kv1.2 potassium channel. Mol Pharm. 2015 Apr 6;12(4):1299-307. doi: 10.1021/acs.molpharmaceut.5b00023. PubMed PMID: 25734225. 6: Hao B, Chen ZW, Zhou XJ, Zimin PI, Miljanich GP, Wulff H, Wang YX. Identification of phase-I metabolites and chronic toxicity study of the Kv1.3 blocker PAP-1 (5-(4-phenoxybutoxy)psoralen) in the rat. Xenobiotica. 2011 Mar;41(3):198-211. doi: 10.3109/00498254.2010.532886. PubMed PMID: 21070145; PubMed Central PMCID: PMC3644211. 7: Stokely ME, Garg P, Bhat MA, Koulen P. Transient 5-(4-phenylbutoxy)psoralen (PAP-1) treatment dissociates developing pathologies in autoimmune optic neuritis into two distinct pathology profiles. J Neurosci Res. 2008 Jul;86(9):2111-24. doi: 10.1002/jnr.21645. PubMed PMID: 18335521. 8: Azam P, Sankaranarayanan A, Homerick D, Griffey S, Wulff H. Targeting effector memory T cells with the small molecule Kv1.3 blocker PAP-1 suppresses allergic contact dermatitis. J Invest Dermatol. 2007 Jun;127(6):1419-29. PubMed PMID: 17273162; PubMed Central PMCID: PMC1929164. 9: Cidad P, Novensà L, Garabito M, Batlle M, Dantas AP, Heras M, López-López JR, Pérez-García MT, Roqué M. Erratum to: K(+) Channels Expression in Hypertension After Arterial Injury, and Effect of Selective Kv1.3 Blockade with PAP-1 on Intimal Hyperplasia Formation. Cardiovasc Drugs Ther. 2015 Apr;29(2):199-200. doi: 10.1007/s10557-015-6578-5. PubMed PMID: 25732511. 10: Schmitz A, Sankaranarayanan A, Azam P, Schmidt-Lassen K, Homerick D, Hänsel W, Wulff H. 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. PubMed PMID: 16099841. 11: Zou Z, Wang Y, Jiang H. Manduca sexta prophenoloxidase activating proteinase-1 (PAP-1) gene: organization, expression, and regulation by immune and hormonal signals. Insect Biochem Mol Biol. 2005 Jun;35(6):627-36. PubMed PMID: 15857768; PubMed Central PMCID: PMC2020815. 12: Leanza L, Trentin L, Becker KA, Frezzato F, Zoratti M, Semenzato G, Gulbins E, Szabo I. Clofazimine, Psora-4 and PAP-1, inhibitors of the potassium channel Kv1.3, as a new and selective therapeutic strategy in chronic lymphocytic leukemia. Leukemia. 2013 Aug;27(8):1782-5. doi: 10.1038/leu.2013.56. PubMed PMID: 23426166. 13: Maita H, Kitaura H, Ariga H, Iguchi-Ariga SM. CIR, a corepressor of CBF1, binds to PAP-1 and effects alternative splicing. Exp Cell Res. 2005 Feb 15;303(2):375-87. PubMed PMID: 15652350. 14: Maita H, Kitaura H, Ariga H, Iguchi-Ariga SM. Association of PAP-1 and Prp3p, the products of causative genes of dominant retinitis pigmentosa, in the tri-snRNP complex. Exp Cell Res. 2005 Jan 1;302(1):61-8. PubMed PMID: 15541726. 15: Maita H, Kitaura H, Keen TJ, Inglehearn CF, Ariga H, Iguchi-Ariga SM. PAP-1, the mutated gene underlying the RP9 form of dominant retinitis pigmentosa, is a splicing factor. Exp Cell Res. 2004 Nov 1;300(2):283-96. PubMed PMID: 15474994. 16: Leung K. (99m)Tc-Mercaptoacetyl-Gly-Gly-Gly-PAP-1. 2008 Aug 8 [updated 2008 Aug 15]. Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013. Available from http://www.ncbi.nlm.nih.gov/books/NBK24577/ PubMed PMID: 20641925. 17: Maita H, Harada Y, Nagakubo D, Kitaura H, Ikeda M, Tamai K, Takahashi K, Ariga H, Iguchi-Ariga SM. PAP-1, a novel target protein of phosphorylation by pim-1 kinase. Eur J Biochem. 2000 Aug;267(16):5168-78. PubMed PMID: 10931201. 18: Straub SV, Perez SM, Tan B, Coughlan KA, Trebino CE, Cosgrove P, Buxton JM, Kreeger JM, Jackson VM. Pharmacological inhibition of Kv1.3 fails to modulate insulin sensitivity in diabetic mice or human insulin-sensitive tissues. Am J Physiol Endocrinol Metab. 2011 Aug;301(2):E380-90. doi: 10.1152/ajpendo.00076.2011. PubMed PMID: 21586699. 19: Nguyen HM, Grössinger EM, Horiuchi M, Davis KW, Jin LW, Maezawa I, Wulff H. Differential Kv1.3, KCa3.1, and Kir2.1 expression in "classically" and "alternatively" activated microglia. Glia. 2017 Jan;65(1):106-121. doi: 10.1002/glia.23078. PubMed PMID: 27696527; PubMed Central PMCID: PMC5113690. 20: Zimin PI, Garic B, Bodendiek SB, Mahieux C, Wulff H, Zhorov BS. Potassium channel block by a tripartite complex of two cationophilic ligands and a potassium ion. Mol Pharmacol. 2010 Oct;78(4):588-99. doi: 10.1124/mol.110.064014. PubMed PMID: 20601455; PubMed Central PMCID: PMC2981387.