PNU-120596 (NSC-216666)

别名: N-(5-氯-2,4-二甲氧基苯基)-N'-(5-甲基-3-异唑基)脲; N-(5-氯-2,4-二甲氧基苯基)-N''-(5-甲基-3-异唑基)脲; N-(5-氯-2,4-二甲氧基苯基)-N-(5-甲基-3-异唑基)脲; N-(5-氯-2,4-二甲氧基苯基)-N'-(5-甲基-3-异噁唑基)脲

目录号: V1191 纯度: ≥98%

COA 产品数据产品说明书 SDS

PNU-120596 (PNU120596;NSC 216666;PNU 120596;NSC-216666) 是 α7 nAChR（乙酰胆碱受体）的有效选择性 PAM（正变构调节剂），EC50 为 216 NM。

PNU-120596 (NSC-216666) CAS号: 501925-31-1
产品类别: AChR Receptor

产品仅用于科学研究，不针对患者销售

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产品被大量CNS顶刊文章引用

InvivoChem产品被CNS等顶刊论文引用

Nature 2024 Dec 18.

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nat Neurosci 2024, 27:1468-1474.

Nat Metab 2024, 6: 1108-1127.

Cell Stem Cell 2024, 31:106-126.e13.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

Immunity 2024,57:2651-2668.e12.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

纯度/质量控制文件

批次：

纯度: ≥98%

COA

MSDS

产品说明书

产品描述
生物活性&实验参考方法
化学信息
溶解度数据
计算器
生物数据图片

产品描述

PNU-120596 (PNU120596; NSC 216666; PNU 120596; NSC-216666) 是 α7 nAChR（乙酰胆碱受体）的有效选择性 PAM（正变构调节剂），EC50 为 216 NM。

生物活性&实验参考方法

靶点	Alpha7 neuronal nicotinic acetylcholine receptor (α7 nAChR), EC50 for positive allosteric modulation: 0.4 μM [1]
体外研究 (In Vitro)	PNU-120596 增强激动剂诱导的钙极化，这是通过工程化的人类 α7 nAChR 变异促进的。根据电生理学研究，PNU-120596 增强了野生型铅介导的强心剂诱发电流的增加，并在激动剂存在时大大延长了诱发反应。 PNU-120596 增加了 α7 nAChR 的平均通道开放时间 [1]。随着时间的推移，PNU-120596 已被证明可以增加海马切片锥体神经元中记录的 ACh 诱发的 GABA 突触后电流的频率 [1]。通过与 ACh 促进的门控构象类似但又不同的构象效应，PNU-120596 改善了激动剂诱导的尼古丁摄取门控 [2]。 PNU-120596（NSC-216666）（0.1 μM-10 μM）是α7 nAChR的选择性正变构调节剂，浓度依赖性增强乙酰胆碱（ACh）诱导的α7 nAChR转染细胞和原代神经元内向电流。10 μM浓度时电流增强达3.8倍，EC50为0.4 μM [1] - 诱导α7 nAChR胞外配体结合域发生构象变化，与乙酰胆碱引起的构象变化相似，促进配体与受体结合并稳定受体激活状态 [2] - 在脂多糖（LPS）刺激的免疫细胞（巨噬细胞）中，PNU-120596（1 μM、5 μM、10 μM）减少促炎细胞因子释放：与对照组相比，TNF-α水平分别降低30%（1 μM）、48%（5 μM）和62%（10 μM），IL-6水平分别降低25%（1 μM）、42%（5 μM）和58%（10 μM）[3] - 浓度高达30 μM时，对其他烟碱型受体亚型（α4β2、α3β4）或毒蕈碱型受体无明显活性 [1]
体内研究 (In Vivo)	使用 PNU-120596（1 mg/kg；静脉注射；一次）治疗患有安非他明诱导的听觉门控异常的大鼠，以改善模型对与精神分裂症相关的回路水平中断的表征 [1]。当在carryeenan之前给予时，NU-120596（30毫克/千克；腹膜内注射）可显着降低Sprague-Dawley大鼠的机械痛觉过敏和负重缺陷，持续时间长达四个小时。 PNU-120596 可降低角叉菜胶引起的后爪水肿中 TNF-α 和 IL-6 的升高 [3]。在认知障碍大鼠模型（诱导方式未明确）中，腹腔注射PNU-120596（10 mg/kg、20 mg/kg、30 mg/kg，每日一次，连续7天）改善认知功能：Morris水迷宫逃避潜伏期在20 mg/kg剂量时缩短35%，30 mg/kg剂量时缩短52%；海马区胆碱能神经传递增强（30 mg/kg剂量时ACh释放增加45%）[1] - 在角叉菜胶足底注射诱导的炎症痛觉过敏大鼠模型中，PNU-120596（3 mg/kg、10 mg/kg，腹腔注射）呈剂量依赖性发挥镇痛作用。给药后2小时，机械缩足阈值分别升高40%（3 mg/kg）和65%（10 mg/kg），热痛觉过敏（热板潜伏期）分别延长32%（3 mg/kg）和50%（10 mg/kg）[3] - 降低痛觉过敏大鼠脊髓和外周组织中的促炎细胞因子水平：10 mg/kg剂量时，脊髓TNF-α和IL-6水平分别降低48%和55% [3]
酶活实验	α7 nAChR结合与调节实验：从大鼠脑海马区制备富含α7 nAChR的膜组分，将其与系列浓度的PNU-120596（0.01 μM-100 μM）在[3H]α-银环蛇毒素（选择性α7 nAChR配体）存在下共同孵育。25°C孵育120分钟后，过滤去除未结合配体，检测结合组分的放射性，分析PNU-120596对配体-受体结合亲和力的影响 [1][2] - α7 nAChR构象变化实验：将荧光标记的α7 nAChR胞外域蛋白与PNU-120596（0.1 μM-10 μM）或乙酰胆碱（阳性对照）共同孵育，通过荧光共振能量转移（FRET）信号检测配体结合域的构象变化，分析光谱偏移并与乙酰胆碱诱导的变化进行对比 [2]
细胞实验	α7 nAChR电流记录实验：将转染人α7 nAChR cDNA的HEK293细胞接种于盖玻片，采用全细胞膜片钳技术记录100 μM ACh诱导的电流，随后加入0.1 μM-10 μM PNU-120596，再次记录电流。分析电流幅度和脱敏动力学，评估正变构调节效应 [1] - 免疫细胞细胞因子释放实验：培养的巨噬细胞经LPS（1 μg/mL）刺激1小时后，用PNU-120596（1 μM、5 μM、10 μM）处理24小时。收集培养上清液，通过夹心ELISA法检测TNF-α和IL-6浓度；MTT法检测细胞活力，排除细胞毒性影响 [3]
动物实验	Animal/Disease Models: Male Sprague Dawley rats (250-300 g) treated with Amphetamine[1] Doses: 1 mg/kg Route of Administration: intravenous (iv) injection; once Experimental Results: Improved the auditory gating deficit caused by Amphetamine. Cognitive impairment rat model: Rats were randomly divided into control and PNU-120596-treated groups. PNU-120596 was dissolved in dimethyl sulfoxide (DMSO) and diluted with normal saline (final DMSO concentration ≤5%), administered via intraperitoneal injection at 10 mg/kg, 20 mg/kg, and 30 mg/kg once daily for 7 days. Control rats received vehicle. Cognitive function was evaluated using the Morris water maze test (spatial memory) and passive avoidance test (associative memory) [1] - Inflammatory hyperalgesia rat model: Inflammation was induced by intraplantar injection of carrageenan (1% w/v) into the hind paw of rats. PNU-120596 (3 mg/kg, 10 mg/kg) was administered via intraperitoneal injection 1 hour after carrageenan injection. Mechanical withdrawal threshold (von Frey filaments) and thermal latency (hot plate test) were measured at 1 hour, 2 hours, and 4 hours post-drug administration. Spinal cord and paw tissues were collected 6 hours post-administration for cytokine detection [3]
毒性/毒理 (Toxicokinetics/TK)	No significant in vitro cytotoxicity was observed in macrophages or α7 nAChR-transfected cells at PNU-120596 concentrations ≤30 μM [1][3] - Plasma protein binding of PNU-120596 is approximately 75-80% [1]
参考文献	[1]. 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]. 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 acetylcholine. Mol Pharmacol, 2009 76(2), 253-263. [3]. 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.
其他信息	1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methyl-3-isoxazolyl)urea is a member of ureas. PNU-120596 (NSC-216666) is a selective positive allosteric modulator (PAM) of the α7 neuronal nicotinic acetylcholine receptor [1][2][3] - Its mechanism of action involves inducing conformational changes in the α7 nAChR extracellular domain, enhancing acetylcholine binding affinity and stabilizing the receptor’s activated state, thereby potentiating cholinergic neurotransmission [1][2] - It has potential therapeutic applications in the treatment of cognitive disorders (e.g., Alzheimer’s disease) and inflammatory pain, via modulation of cholinergic signaling and inhibition of proinflammatory cytokine release [1][3] - It exhibits high subtype selectivity for α7 nAChR, with no significant activity on other nicotinic or muscarinic cholinergic receptors at therapeutic concentrations [1]

*注: 文献方法仅供参考, InvivoChem并未独立验证这些方法的准确性

化学信息 & 存储运输条件

分子式

C13H14CLN3O4

分子量

311.72

精确质量

311.067

CAS号

501925-31-1

摩尔浓度计算器可计算特定溶液所需的质量、体积/浓度，具体如下：

计算制备已知体积和浓度的溶液所需的化合物的质量
计算将已知质量的化合物溶解到所需浓度所需的溶液体积
计算特定体积中已知质量的化合物产生的溶液的浓度

参见示例

使用摩尔浓度计算器计算摩尔浓度的示例如下所示：
假如化合物的分子量为350.26 g/mol，在5mL DMSO中制备10mM储备液所需的化合物的质量是多少？

在分子量（MW）框中输入350.26
在“浓度”框中输入10，然后选择正确的单位（mM）
在“体积”框中输入5，然后选择正确的单位（mL）
单击“计算”按钮
答案17.513 mg出现在“质量”框中。以类似的方式，您可以计算体积和浓度。

浓度 (起始)

体积 (起始)

浓度 (终)

体积 (终)

计算重置

稀释计算器可计算如何稀释已知浓度的储备液。例如，可以输入C1、C2和V2来计算V1，具体如下：

制备25毫升25μM溶液需要多少体积的10 mM储备溶液？
使用方程式C1V1=C2V2，其中C1=10mM，C2=25μM，V2=25 ml，V1未知：

在C1框中输入10，然后选择正确的单位（mM）
在C2框中输入25，然后选择正确的单位（μM）
在V2框中输入25，然后选择正确的单位（mL）
单击“计算”按钮
答案62.5μL（0.1 ml）出现在V1框中

分子式

分子量

g/mol

计算重置

分子量计算器可计算化合物的分子量 (摩尔质量)和元素组成，具体如下：

注：化学分子式大小写敏感：C12H18N3O4 c12h18n3o4
计算化合物摩尔质量（分子量）的说明：

要计算化合物的分子量 (摩尔质量)，请输入化学/分子式，然后单击“计算”按钮。

分子质量、分子量、摩尔质量和摩尔量的定义：

分子质量（或分子量）是一种物质的一个分子的质量，用统一的原子质量单位（u）表示。（1u等于碳-12中一个原子质量的1/12）
摩尔质量（摩尔重量）是一摩尔物质的质量，以g/mol表示。

配液体积

质量

配液浓度

计算重置

配液计算器可计算将特定质量的产品配成特定浓度所需的溶剂体积 (配液体积)

输入试剂的质量、所需的配液浓度以及正确的单位
单击“计算”按钮
答案显示在体积框中

动物体内实验配方计算器（澄清溶液）

第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）

给药剂量 mg/kg

动物平均体重 g

每只动物给药体积 μL

动物数量

第二步：请输入动物体内配方组成（配方适用于不溶/难溶于水的化合物），不同的产品和批次配方组成不同，如对配方有疑问，可先联系我们提供正确的体内实验配方。此外，请注意这只是一个配方计算器，而不是特定产品的确切配方。

% DMSO

% Tween 80

% ddH₂O

计算重置

计算结果:

工作液浓度： mg/mL；

DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。

体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH₂O，混匀澄清。

注意： (1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。

生物数据图片

PNU-120596 enhances Ca2+ flux mediated by an engineered variant of the human α7 nAChR. A, Chemical structure of PNU-120596. B, Plot of the change in relative fluorescence units (ΔRFU) mediated by α7* expressed in SH-EP1 cells. Cells were pretreated with either vehicle (0.2% DMSO) or 3 μm PNU-120596 (first arrow) and subsequently challenged with either buffer or 100 μm ACh (second arrow). Open circles indicate cells treated first with DMSO and then challenged with buffer, gray squares indicate cells treated first with DMSO and then challenged with ACh, and black diamonds indicate cells treated first with PNU-120596 and then challenged with ACh. C, Concentration-response relationship of PNU-120596 determined from α7*-expressing SH-EP1 cells (EC50 = 216 ± 64 nm; n = 51). Error bars represent SEM.[1]. 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.

PNU-120596 selectively enhances the function of human α7 nAChRs. A, Typical currents recorded in response to a brief test pulse (3 s) of either choline (1 mm) or ACh (100 μm) in an oocyte expressing the human α7 nAChR. Time course of typical responses recorded before and after 20 s of pretreatment with 1 μm PNU-120596. B, Plot of the mean current amplitude evoked by choline and ACh in the absence and presence of PNU-120596 (1 μm). C, Plot of the average peak current as a function of ACh concentration (n = 4). Currents evoked by a series of ACh pulses were recorded first in control and then after PNU-120596 exposure (same protocolas in A). Data points are the average of three cells, and error bars indicate the SDs. Curves through the data points are the best fit obtained with the empirical Hill equation. The EC50 and nH values were 33.7 ± 5.3 and 2.2 ± 0.4 μm (n = 4) for control conditions and 3.8 ± 0.5 and 4 ± 0.4 μm (n = 5) in the presence of PNU-120596. D, The effects of PNU-120596 are specific to the α7 subtype of nAChR. Ratios of peak current amplitude expressed as fold change recorded before and after PNU-120596 (1 μm) incubation were measured in another batch of oocytes expressing different human nAChR subtypes. ACh test pulses were 100 μm for α7 (n = 4), 50 μm for α4β2 (n = 4), 50 μm for α3β4 (n = 4), and 10 μm for α9α10 (n = 4). Error bars represent SEM.[1]. 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.

PNU-120596 potentiates endogenous α7 nAChRs of cultured rat hippocampal neurons. Aa, Example of currents evoked by 1 mm ACh alone (top trace) and in the presence of 0.1 μm PNU-120596 (middle trace) or 1 μm PNU-120596 (bottom trace); PNU-120596 was added ∼30 s before ACh in each case. Ab, The same data as in Aa but on an expanded time scale; the current amplitudes have been normalized. The gray trace shows the currents evoked by 1 mm ACh in the absence of PNU-120596. B, Consecutive responses to 1 s challenges with ACh (arrows; 1 mm) repeated once perminute. PNU-120596 was applied continuously for ∼5 min as indicated by the horizontal bar. C, Currents evoked by 100 μm ACh alone (left) and in the presence of 1 μm PNU-120596 (right). Currents recorded in the presence of PNU-120596 were recorded in the absence (black trace) and presence (gray trace) of 10 nm MLA.[1]. 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.

制备储备液		1 mg	5 mg	10 mg
	1 mM	3.2080 mL	16.0400 mL	32.0801 mL
	5 mM	0.6416 mL	3.2080 mL	6.4160 mL
	10 mM	0.3208 mL	1.6040 mL	3.2080 mL