A-317491 Sodium - 半岛电竞官方网址

Molecular Weight (MW)	631.12
Formula	C33H24NNa3O8
CAS No.	475205-49-3 (free acid)
Storage	-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO:>100 mg/mL (176.81 mM)
Water: N/A
Ethanol: >100 mg/mL (176.81 mM)
Solubility (In vivo)	O=C(C1=CC(C(N(CC2=CC=CC(OC3=CC=CC=C3)=C2)[C@H]4CCCC5=C4C=CC=C5)=O)=C(C([O-])=O) C=C1C([O-])=O)[O-].[Na+].[Na+].[Na+]
Synonyms	A-317491 sodium; A317491; A 317491

Molecular Weight (MW)

631.12

Formula

C33H24NNa3O8

CAS No.

475205-49-3 (free acid)

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO:>100 mg/mL (176.81 mM)

Water: N/A

Ethanol: >100 mg/mL (176.81 mM)

Solubility (In vivo)

O=C(C1=CC(C(N(CC2=CC=CC(OC3=CC=CC=C3)=C2)[C@H]4CCCC5=C4C=CC=C5)=O)=C(C([O-])=O) C=C1C([O-])=O)[O-].[Na+].[Na+].[Na+]

Synonyms

A-317491 sodium; A317491; A 317491

In Vitro	In vitro activity: A-317491 does not undergo any detectable metabolism (oxidation or glucuronidation) in in vitro assays using human and rat liver microsomes. It potently blocks recombinant human and rat P2X3 and P2X2/3 receptor-mediated calcium flux (Ki = 22-92 nM) and is highly selective (IC50>10 μM) over other P2 receptors and other neurotransmitter receptors, ion channels, and enzymes. Kinase Assay: A-317491 is a selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors, which inhibits calcium flux mediated by the receptors. The purinergic P2X3 and P2X2/3 receptors are in the peripheral nervous system almost exclusively confined to afferent sensory neurons, where they are found both at peripheral and central synapses. The P2X3 receptor is implicated in both neuropathic and inflammatory pain. It is known that P2X3 and P2X2/3 receptors stimulate the pronociceptive effects of ATP upon activation. Studies indicate that the P2X3 receptor is implicated in both neuropathic and inflammatory pain. P2X3 receptor is a promising target for therapeutic intervention in cancer patients for pain management. Cell Assay:
In Vivo	A-317491 is effective in reducing pain associated behavior in several animal models of inflammatory and neuropathic pain when administered systemically. It dose-dependently (ED50 = 30 μmol/kg s.c.) reduces complete Freund's adjuvant-induced thermal hyperalgesia in the rat. A-317491 is most potent (ED50 = 10-15 μmol/kg s.c.) in attenuating both thermal hyperalgesia and mechanical allodynia after chronic nerve constriction injury. Although active in chronic pain models, A-317491 is ineffective (ED50>100 μmol/kg s.c.) in reducing nociception in animal models of acute pain, postoperative pain, and visceral pain. Preliminary pharmacokinetic studies in rats indicate that 10 μmol/kg A-317491 had high (≈80%) systemic bioavailability after s.c. dosing (estimated plasma concentration = 15 μg/ml,>99% protein bound) and a half-life in plasma of 11 h.
Animal model	male Sprague-Dawley rats
Formulation & Dosage	0.01M PBS; 3, 10 and 30 mg/kg; s.c.
References	Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):17179-84; Eur J Pharmacol. 2004 Nov 3;504(1-2):45-53.

In Vitro

In vitro activity: A-317491 does not undergo any detectable metabolism (oxidation or glucuronidation) in in vitro assays using human and rat liver microsomes. It potently blocks recombinant human and rat P2X3 and P2X2/3 receptor-mediated calcium flux (Ki = 22-92 nM) and is highly selective (IC50>10 μM) over other P2 receptors and other neurotransmitter receptors, ion channels, and enzymes.

Kinase Assay: A-317491 is a selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors, which inhibits calcium flux mediated by the receptors. The purinergic P2X3 and P2X2/3 receptors are in the peripheral nervous system almost exclusively confined to afferent sensory neurons, where they are found both at peripheral and central synapses. The P2X3 receptor is implicated in both neuropathic and inflammatory pain. It is known that P2X3 and P2X2/3 receptors stimulate the pronociceptive effects of ATP upon activation. Studies indicate that the P2X3 receptor is implicated in both neuropathic and inflammatory pain. P2X3 receptor is a promising target for therapeutic intervention in cancer patients for pain management.

Cell Assay:

In Vivo

A-317491 is effective in reducing pain associated behavior in several animal models of inflammatory and neuropathic pain when administered systemically. It dose-dependently (ED50 = 30 μmol/kg s.c.) reduces complete Freund's adjuvant-induced thermal hyperalgesia in the rat. A-317491 is most potent (ED50 = 10-15 μmol/kg s.c.) in attenuating both thermal hyperalgesia and mechanical allodynia after chronic nerve constriction injury. Although active in chronic pain models, A-317491 is ineffective (ED50>100 μmol/kg s.c.) in reducing nociception in animal models of acute pain, postoperative pain, and visceral pain. Preliminary pharmacokinetic studies in rats indicate that 10 μmol/kg A-317491 had high (≈80%) systemic bioavailability after s.c. dosing (estimated plasma concentration = 15 μg/ml,>99% protein bound) and a half-life in plasma of 11 h.

Animal model

male Sprague-Dawley rats

Formulation & Dosage

0.01M PBS; 3, 10 and 30 mg/kg; s.c.

References

Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):17179-84; Eur J Pharmacol. 2004 Nov 3;504(1-2):45-53.

CAS NO:	475205-49-3
规格:	≥98%

包装	价格(元)
5mg	电议
10mg	电议
25mg	电议
50mg	电议
100mg	电议
250mg	电议
500mg	电议