CAS 501925-31-1|PNU-120596

Introduction：Basic information about CAS 501925-31-1|PNU-120596, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. PNU-120596 BiologicalActivity
3. Chemical & Physical Properties
4. Safety Information
5. Customs
6. Articles1
7. Synonyms

Common Name	PNU-120596
CAS Number	501925-31-1	Molecular Weight	311.721
Density	1.4±0.1 g/cm3	Boiling Point	385.0±42.0 °C at 760 mmHg
Molecular Formula	C₁₃H₁₄ClN₃O₄	Melting Point	/
MSDS	ChineseUSA	Flash Point	186.6±27.9 °C

Names

Name	1-(5-Chloro-2,4-dimethoxyphenyl)-3-(5-methylisoxazol-3-yl)urea
Synonym	More Synonyms

PNU-120596 BiologicalActivity

Description	PNU-120596 (NSC 216666 ) is a potent and selective positive allosteric α7 nAChR modulator with an EC50 of 0.2 μM.IC50 value: 0.2 uM (EC50) [1] Target: α7in vitro: PNU-120596 increases agonist (Ach)-evoked calcium flux mediated by an engineered variant of the human α7 nAChR. PNU-120596 increases agonists (choline and ACh)-evoked currents mediated by wild-type receptors and also demonstrates a pronounced prolongation of the evoked response in the continued presence of agonist in Xenopus oocytes. PNU-120596 increases the channel mean open time ofα7 nAChRs but has no effect on ion selectivity and relatively little, if any, effect on unitary conductance. When applied to acute hippocampal slices, PNU-120596 increases the frequency of ACh-evoked GABAergic postsynaptic currents measured in pyramidal neurons; this effect is suppressed by TTX, suggesting that PNU-120596 modulates the function of α7 nAChRs located on the somatodendritic membrane of hippocampal interneurons [1]. Besides the positive modulation to α7 nAChR, PNU-120596 induces a profound retardation of the kinetics of desensitization, raising the potential of Ca2+-induced toxicity through excessive stimulation of α7 nAChR [2]. PNU-120596 causes changes in cysteine accessibility at the inner beta sheet, transition zone and agonist binding site while binding to α7 nAChR. Binding sites for PNU-120596 are not in the agonist-binding sites and PNU-120596 enhances agonist-evoked gating of nicotinic receptors by eliciting conformational effects that are similar but nonidentical to the gating conformations promoted by Ach [3].in vivo: Systemic administration of PNU-120596 (1 mg/kg) to rats improves the auditory gating deficit caused by amphetamine, a model proposed to reflect a circuit level disturbance associated with schizophrenia. [1] When administered prior to Carrageenan, 30 mg/kg PNU-1230596 significantly blunts mechanical hyperalgesia and weight bearing deficits for up to 4 hours. PNU-120596 attenuates the carrageenan-induced increase in levels of TNF-α and IL-6 within the hindpaw oedema, diclofenac only attenuated IL-6 levels. Established mechanical hyperalgesia induced by Carrageenan or CFA is also partially reversed by PNU-120596 [4].
Related Catalog	Signaling Pathways >>Membrane Transporter/Ion Channel >>nAChRSignaling Pathways >>Neuronal Signaling >>nAChRResearch Areas >>Neurological Disease
References	[1]. Hurst RS, et al. A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization. J Neurosci, 2005, 25(17), 4396-4405. [2]. Ng HJ, et al. Nootropic alpha7 nicotinic receptor allosteric modulator derived from GABAA receptor modulators. Proc Natl Acad Sci USA, 2007, 104(19), 8059-8064. [3]. Barron SC, et al. An allosteric modulator of alpha7 nicotinic receptors, N-(5-Chloro-2,4-dimethoxyphenyl)-N'-(5-methyl-3-isoxazolyl)-urea (PNU-120596), causes conformational changes in the extracellular ligand binding domain similar to those caused by ace [4]. Munro G, et al. The α7 nicotinic ACh receptor agonist compound B and positive allosteric modulator PNU-120596 both alleviate inflammatory hyperalgesia and cytokine release in the rat. Br J Pharmacol, 2012, doi: 10.1111/j.1476-5381.2012.02003.x

Description

PNU-120596 (NSC 216666 ) is a potent and selective positive allosteric α7 nAChR modulator with an EC50 of 0.2 μM.IC50 value: 0.2 uM (EC50) [1] Target: α7in vitro: PNU-120596 increases agonist (Ach)-evoked calcium flux mediated by an engineered variant of the human α7 nAChR. PNU-120596 increases agonists (choline and ACh)-evoked currents mediated by wild-type receptors and also demonstrates a pronounced prolongation of the evoked response in the continued presence of agonist in Xenopus oocytes. PNU-120596 increases the channel mean open time ofα7 nAChRs but has no effect on ion selectivity and relatively little, if any, effect on unitary conductance. When applied to acute hippocampal slices, PNU-120596 increases the frequency of ACh-evoked GABAergic postsynaptic currents measured in pyramidal neurons; this effect is suppressed by TTX, suggesting that PNU-120596 modulates the function of α7 nAChRs located on the somatodendritic membrane of hippocampal interneurons [1]. Besides the positive modulation to α7 nAChR, PNU-120596 induces a profound retardation of the kinetics of desensitization, raising the potential of Ca2+-induced toxicity through excessive stimulation of α7 nAChR [2]. PNU-120596 causes changes in cysteine accessibility at the inner beta sheet, transition zone and agonist binding site while binding to α7 nAChR. Binding sites for PNU-120596 are not in the agonist-binding sites and PNU-120596 enhances agonist-evoked gating of nicotinic receptors by eliciting conformational effects that are similar but nonidentical to the gating conformations promoted by Ach [3].in vivo: Systemic administration of PNU-120596 (1 mg/kg) to rats improves the auditory gating deficit caused by amphetamine, a model proposed to reflect a circuit level disturbance associated with schizophrenia. [1] When administered prior to Carrageenan, 30 mg/kg PNU-1230596 significantly blunts mechanical hyperalgesia and weight bearing deficits for up to 4 hours. PNU-120596 attenuates the carrageenan-induced increase in levels of TNF-α and IL-6 within the hindpaw oedema, diclofenac only attenuated IL-6 levels. Established mechanical hyperalgesia induced by Carrageenan or CFA is also partially reversed by PNU-120596 [4].

Related Catalog

Signaling Pathways >>Membrane Transporter/Ion Channel >>nAChRSignaling Pathways >>Neuronal Signaling >>nAChRResearch Areas >>Neurological Disease

References

[1]. Hurst RS, et al. A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization. J Neurosci, 2005, 25(17), 4396-4405.

[2]. Ng HJ, et al. Nootropic alpha7 nicotinic receptor allosteric modulator derived from GABAA receptor modulators. Proc Natl Acad Sci USA, 2007, 104(19), 8059-8064.

[3]. Barron SC, et al. An allosteric modulator of alpha7 nicotinic receptors, N-(5-Chloro-2,4-dimethoxyphenyl)-N'-(5-methyl-3-isoxazolyl)-urea (PNU-120596), causes conformational changes in the extracellular ligand binding domain similar to those caused by ace

[4]. Munro G, et al. The α7 nicotinic ACh receptor agonist compound B and positive allosteric modulator PNU-120596 both alleviate inflammatory hyperalgesia and cytokine release in the rat. Br J Pharmacol, 2012, doi: 10.1111/j.1476-5381.2012.02003.x

Chemical & Physical Properties

Density	1.4±0.1 g/cm3
Boiling Point	385.0±42.0 °C at 760 mmHg
Molecular Formula	C₁₃H₁₄ClN₃O₄
Molecular Weight	311.721
Flash Point	186.6±27.9 °C
Exact Mass	311.067291
PSA	85.62000
LogP	2.14
Appearance of Characters	white to off-white
Vapour Pressure	0.0±0.9 mmHg at 25°C
Index of Refraction	1.625
InChIKey	CEIIEALEIHQDBX-UHFFFAOYSA-N
SMILES	COc1cc(OC)c(NC(=O)Nc2cc(C)on2)cc1Cl
Storage condition	Desiccate at +4°C
Water Solubility	DMSO: >10mg/mL

Safety Information

RIDADR	NONH for all modes of transport
HS Code	2934999090

Customs

HS Code	2934999090
Summary	2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles1

Activation of Alpha 7 Cholinergic Nicotinic Receptors Reduce Blood-Brain Barrier Permeability following Experimental Traumatic Brain Injury.

J. Neurosci. 36 , 2809-18, (2016)

Traumatic brain injury (TBI) is a major human health concern that has the greatest impact on young men and women. The breakdown of the blood-brain barrier (BBB) is an important pathological consequenc...

Synonyms

1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methylisoxazol-3-yl)urea

Urea, N-(5-chloro-2,4-dimethoxyphenyl)-N'-(5-methyl-3-isoxazolyl)-

1-(5-Chloro-2,4-dimethoxyphenyl)-3-(5-methyl-1,2-oxazol-3-yl)urea

PNU-120596

PNU120596

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