CAS 870653-45-5|PAP-1

Introduction：Basic information about CAS 870653-45-5|PAP-1, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. PAP-1 BiologicalActivity
3. Chemical & Physical Properties
4. Safety Information
5. Customs
6. Synonyms

Common Name	PAP-1
CAS Number	870653-45-5	Molecular Weight	350.365
Density	1.3±0.1 g/cm3	Boiling Point	555.8±50.0 °C at 760 mmHg
Molecular Formula	C₂₁H₁₈O₅	Melting Point	/
MSDS	USA	Flash Point	289.9±30.1 °C
Symbol	GHS08	Signal Word	Danger

Names

Name	5-(4-Phenoxybutoxy)psoralen
Synonym	More Synonyms

PAP-1 BiologicalActivity

Description	PAP-1 is a selective inhibitor of Kv1.3, voltage-gated K+ channel. PAP-1 (EC50=2 nM) potently inhibits human T effector memory cell proliferation and delayed hypersensitivity. IC50 value: 2 nM (EC50) [1]in vitro: blocks Kv1.3 in a use-dependent manner, with a Hill coefficient of 2 and an EC50 of 2 nM, by preferentially binding to the C-type inactivated state of the channel. PAP-1 is 23-fold selective over Kv1.5, 33- to 125-fold selective over other Kv1-family channels, and 500- to 7500-fold selective over Kv2.1, Kv3.1, Kv3.2, Kv4.2, HERG, calcium-activated K+ channels, Na+,Ca2+, and Cl- channels [1]. The blockade of Kv1.3 results in membrane depolarization and inhibition of TEM proliferation and function. In this study, the in vitro effects of PAP-1 on T cells and the in vivo toxicity and pharmacokinetics (PK) were examined in rhesus macaques (RM) with the ultimate aim of utilizing PAP-1 to define the role of TEMs in RM infected with simian immunodeficiency virus (SIV). Electrophysiologic studies on T cells in RM revealed a Kv1.3 expression pattern similar to that in human T cells. Thus, PAP-1 effectively suppressed TEM proliferation in RM [2].in vivo: PAP-1 does not exhibit cytotoxic or phototoxic effects, is negative in the Ames test, and affects cytochrome P450-dependent enzymes only at micromolar concentrations. PAP-1 potently inhibits the proliferation of human TEM cells and suppresses delayed type hypersensitivity, a TEM cell-mediated reaction, in rats [1]. When administered intravenously, PAP-1 showed a half-life of 6.4 hrs; the volume of distribution suggested extensive distribution into extravascular compartments. When orally administered, PAP-1 was efficiently absorbed. Plasma concentrations in RM undergoing a 30-day, chronic dosing study indicated that PAP-1 levels suppressive to TEMs in vitro can be achieved and maintained in vivo at a non-toxic dose [2].
Related Catalog	Signaling Pathways >>Membrane Transporter/Ion Channel >>Potassium ChannelResearch Areas >>Inflammation/Immunology
References	[1]. Schmitz A, et al. 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]. Pereira LE, et al. 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.

Description

PAP-1 is a selective inhibitor of Kv1.3, voltage-gated K+ channel. PAP-1 (EC50=2 nM) potently inhibits human T effector memory cell proliferation and delayed hypersensitivity. IC50 value: 2 nM (EC50) [1]in vitro: blocks Kv1.3 in a use-dependent manner, with a Hill coefficient of 2 and an EC50 of 2 nM, by preferentially binding to the C-type inactivated state of the channel. PAP-1 is 23-fold selective over Kv1.5, 33- to 125-fold selective over other Kv1-family channels, and 500- to 7500-fold selective over Kv2.1, Kv3.1, Kv3.2, Kv4.2, HERG, calcium-activated K+ channels, Na+,Ca2+, and Cl- channels [1]. The blockade of Kv1.3 results in membrane depolarization and inhibition of TEM proliferation and function. In this study, the in vitro effects of PAP-1 on T cells and the in vivo toxicity and pharmacokinetics (PK) were examined in rhesus macaques (RM) with the ultimate aim of utilizing PAP-1 to define the role of TEMs in RM infected with simian immunodeficiency virus (SIV). Electrophysiologic studies on T cells in RM revealed a Kv1.3 expression pattern similar to that in human T cells. Thus, PAP-1 effectively suppressed TEM proliferation in RM [2].in vivo: PAP-1 does not exhibit cytotoxic or phototoxic effects, is negative in the Ames test, and affects cytochrome P450-dependent enzymes only at micromolar concentrations. PAP-1 potently inhibits the proliferation of human TEM cells and suppresses delayed type hypersensitivity, a TEM cell-mediated reaction, in rats [1]. When administered intravenously, PAP-1 showed a half-life of 6.4 hrs; the volume of distribution suggested extensive distribution into extravascular compartments. When orally administered, PAP-1 was efficiently absorbed. Plasma concentrations in RM undergoing a 30-day, chronic dosing study indicated that PAP-1 levels suppressive to TEMs in vitro can be achieved and maintained in vivo at a non-toxic dose [2].

Related Catalog

Signaling Pathways >>Membrane Transporter/Ion Channel >>Potassium ChannelResearch Areas >>Inflammation/Immunology

References

[1]. Schmitz A, et al. 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]. Pereira LE, et al. 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.

Chemical & Physical Properties

Density	1.3±0.1 g/cm3
Boiling Point	555.8±50.0 °C at 760 mmHg
Molecular Formula	C₂₁H₁₈O₅
Molecular Weight	350.365
Flash Point	289.9±30.1 °C
Exact Mass	350.115417
PSA	61.81000
LogP	4.56
Vapour Pressure	0.0±1.5 mmHg at 25°C
Index of Refraction	1.619
InChIKey	KINMYBBFQRSVLL-UHFFFAOYSA-N
SMILES	O=c1ccc2c(OCCCCOc3ccccc3)c3ccoc3cc2o1
Storage condition	2~8°C

Safety Information

Symbol	GHS08
Signal Word	Danger
Hazard Statements	H334
Precautionary Statements	P261-P342 + P311
Personal Protective Equipment	dust mask type N95 (US);Eyeshields;Faceshields;Gloves
Risk Phrases	R42/43
Safety Phrases	22-36/37-45
RIDADR	NONH for all modes of transport
HS Code	2932999099

Customs

HS Code	2932999099
Summary	2932999099. other heterocyclic compounds with oxygen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Synonyms

7H-Furo[3,2-g][1]benzopyran-7-one, 4-(4-phenoxybutoxy)-

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

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

5-(4-Phenoxybutoxy)psoralen

PAP-1

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