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扑蛲灵

扑蛲灵用途

Pyrvinium pamoate是FDA批准的抗蠕虫药物,抑制 WNT 通路信号传导。

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扑蛲灵名称

[ CAS 号 ]:
3546-41-6

[ 中文名 ]:
扑蛲灵

[ 英文名 ]:
Pyrvinium pamoate

[中文别名 ]:

吡维铵

[英文别名 ]:

pyrvinium pamoate

扑蛲灵生物活性

[ 描述 ]:

Pyrvinium pamoate是FDA批准的抗蠕虫药物,抑制 WNT 通路信号传导。

[ 相关类别 ]:

信号通路 >> 干细胞及 Wnt 通路 >> Wnt信号

研究领域 >> 癌症

[体外研究]

Pamvinium pamoate(0-500 nM)以剂量抑制MCF-7(腔),MDA-MB-231(claudin-low),MDA-MB-468(基底样)和SkBr3(HER2-OE)细胞的增殖依赖性方式,对MDA-MB-231细胞系的IC50值为1170±105.0nM。 Pamvinium pamoate显着抑制BCSCs的自我更新和增殖,并抑制具有不同表型的BCSC群体。 Pamvinium pamoate在转录水平显着降低FZD1,FZD10,WNT1,WNT7B,CTNNB1,MYC和LRP5的平均表达水平。此外,Pyrvinium pamoate还可有效下调其他干性基因的表达,包括ALDH1,CD44和ABCG2 [1]。 Pamvinium pamoate以剂量依赖性方式在体外阻断结肠癌细胞生长,抑制浓度(IC50)差异很大,对于具有WNT信号传导突变的结肠癌细胞,范围为0.6至65μM。 Pamvinium pamoate将已知WNT靶基因的信使RNA(mRNA)和蛋白水平降低为c-MYC,从而导致p21的诱导[2]。 Pamvinium pamoate尽管对CK1缺乏疗效,但最终抑制Wnt信号传导[3]。 Pamvinium pamoate对缺血时的心脏成纤维细胞具有特异性毒性(IC50 = 9.5nM)。 Pamvinium pamoate对葡萄糖和谷氨酰胺缺乏条件下心脏成纤维细胞的细胞毒作用[4]。

[体内研究]

在异种移植模型中,Pyrvinium pamoate(500 nM)预处理强烈延迟肿瘤大小和肿瘤重量,并且肿瘤体积显着减少[1]。

[细胞实验]

将Pyrvinium pamoate以1μM的浓度溶解在DMSO中，并以等分试样在-20℃下储存。将细胞（1×10 4）悬浮于200μL培养基中，然后一式五份接种到96孔板中过夜。用指定浓度的Pamvinium pamoate（0-8,000μM）处理细胞。孵育3天后，将CCK8（10μL）加入各孔中，并在37℃下孵育1小时。使用酶标仪在450nm处测量吸光度[1]。

[动物实验]

小鼠：NOD / SCID小鼠在无菌条件下饲养在单独通风的笼子中。对于异种移植，将5×106 Pamvinium pamoate预处理或未处理的乳腺癌细胞（MDA-MB-231）重悬于培养基和Matrigel的1：1混合物中，然后移植到小鼠的第四对乳腺脂肪垫中（4） -6周龄）。注射后，每天通过卡尺测量肿瘤大小并绘制肿瘤生长。到达终点后，处死小鼠并收获肿瘤。所有肿瘤均经福尔马林固定，石蜡包埋苏木精和伊红，并进行免疫组化染色[1]。

[参考文献]

[1]. Xu L, et al. WNT pathway inhibitor pyrvinium pamoate inhibits the self-renewal and metastasis of breast cancer stem cells. Int J Oncol. 2016 Mar;48(3):1175-86.

[2]. Wiegering A, et al. The impact of pyrvinium pamoate on colon cancer cell viability. Int J Colorectal Dis. 2014 Oct;29(10):1189-98.

[3]. Venerando A, et al. Pyrvinium pamoate does not activate protein kinase CK1, but promotes Akt/PKB down-regulation and GSK3 activation. Biochem J. 2013 May 15;452(1):131-7.

[4]. Murakoshi M, et al. An anthelmintic drug, pyrvinium pamoate, thwarts fibrosis and ameliorates myocardial contractile dysfunction in a mouse model of myocardial infarction. PLoS One. 2013 Nov 4;8(11):e79374.

[相关活性小分子]

扑蛲灵物理化学性质

[ 密度 ]:
1.0104 (rough estimate)

[ 沸点 ]:
829.27°C (rough estimate)

[ 熔点 ]:
210-215° (softens at 190°)

[ 分子式 ]:
C₂₆H₂₈N_3.1/₂C₂₃H₁₄O₆

[ 分子量 ]:
575.70

[ PSA ]:
144.82000

[ LogP ]:
12.33840

[ 外观性状 ]:
red

[ 折射率 ]:
1.6400 (estimate)

[ 储存条件 ]:
room temp

[ 水溶解性 ]:
DMSO: >10mg/mL

扑蛲灵MSDS

详细MSDS(安全技术说明书)

扑蛲灵毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: VC3543500

CAS REGISTRY NUMBER :: 3546-41-6

LAST UPDATED :: 199512

DATA ITEMS CITED :: 11

MOLECULAR FORMULA :: C75-H70-N6-O6

MOLECULAR WEIGHT :: 1151.51

WISWESSER LINE NOTATION :: T66 BKJ B1 HN1&1 C1U1- CT5NJ AR& B1 E1 &L66J CQ DVO B1- BL66J CQ DVO

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 5 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 200 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - tremor

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 15 gm/kg/30D-C

TOXIC EFFECTS :: Endocrine - other changes Related to Chronic Data - death Related to Chronic Data - changes in testicular weight

MUTATION DATA

TYPE OF TEST :: Gene conversion and mitotic recombination

TEST SYSTEM :: Yeast - Saccharomyces cerevisiae

DOSE/DURATION :: 400 umol/L

REFERENCE :: MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 187,79,1987 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 81965 No. of Facilities: 805 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 805 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 81965 No. of Facilities: 19 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 774 (estimated) No. of Female Employees: 337 (estimated)

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扑蛲灵安全信息

[ 符号 ]:

GHS07, GHS08

[ 信号词 ]:
Warning

[ 危害声明 ]:
H302 + H312 + H332-H315-H319-H335-H351

[ 警示性声明 ]:
P261-P280-P301 + P312 + P330-P305 + P351 + P338

[ 危害码 (欧洲) ]:
Xn

[ 风险声明 (欧洲) ]:
20/21/22-36/37/38-40

[ 安全声明 (欧洲) ]:
26-36

[ 危险品运输编码 ]:
NONH for all modes of transport

扑蛲灵文献

Casein kinase 1 suppresses activation of REST in insulted hippocampal neurons and halts ischemia-induced neuronal death.

J. Neurosci. 34(17) , 6030-9, (2014)

Repressor Element-1 (RE1) Silencing Transcription Factor/Neuron-Restrictive Silencer Factor (REST/NRSF) is a gene-silencing factor that is widely expressed during embryogenesis and plays a strategic r...

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扑蛲灵