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咯利普兰

咯利普兰用途

Rolipram 是一种选择性的磷酸二酯酶 PDE4 抑制剂,抑制 PDE4A,PDE4B 和 PDE4D,的 IC50 分别为 3 nM,130 nM 和 240 nM。

咯利普兰名称

[ CAS 号 ]:
61413-54-5

[ 中文名 ]:
咯利普兰

[ 英文名 ]:
rolipram

[中文别名 ]:

诺普利兰

[英文别名 ]:

(R,S)-Rolipram
(±)-Rolipram
Adeo
[3H]-Rolipram
Rolipram
EINECS 262-771-1
Rolipramum [Latin]
T5MVTJ DR DO1 CO- AL6TJ
MFCD00270906

咯利普兰生物活性

[ 描述 ]:

Rolipram 是一种选择性的磷酸二酯酶 PDE4 抑制剂,抑制 PDE4A,PDE4B 和 PDE4D,的 IC50 分别为 3 nM,130 nM 和 240 nM。

[ 相关类别 ]:

信号通路 >> 代谢酶/蛋白酶 >> 磷酸二酯酶(PDE)

研究领域 >> 神经疾病

[ 靶点 ]

IC50: 3 nM (PDE4A), 130 nM (PDE4B), 240 nM (PDE4D)[1]

[体外研究]

PDE4选择性抑制剂咯利普兰类似地抑制免疫纯化的PDE4B和PDE4D活性,IC50约为50。分别为130 nM和240 nM。相比之下,咯利普兰抑制免疫纯化的PDE4A活性,IC50约为3 nM。咯利普兰以剂量依赖的方式增加U937细胞中cAMP-反应元件结合蛋白(CREB)的磷酸化,这意味着存在高亲和力(IC50约1nM)和低亲和力(IC50约120nM)组件。咯利普兰以简单的单调方式剂量依赖性地抑制IFN-γ刺激的p38MAPK磷酸化,IC50约为50。 290 nM [1]。咯利普兰是一种选择性PDE4抑制剂,可抑制所有PDE4亚型A,B,C和D.咯利普兰以剂量依赖性方式抑制LPS诱导的TNF产生(IC50 25.9 nM),并且在2μM药物浓度下观察到最大/次最大抑制在J774细胞中[2]。

[体内研究]

LPS在来自WT小鼠的腹膜巨噬细胞(PM)中诱导TNF mRNA和蛋白质表达,并且显然(分别由TNF mRNA和TNF蛋白分别为74％和63％)被咯利普兰抑制。与来自WT小鼠的PM相比,来自MKP-1(-/-)小鼠的PM中LPS诱导的TNF产生增强,这与公布的结果一致。有趣的是,来自咯普仑的TNF mRNA和蛋白表达的抑制在来自MKP-1(-/-)小鼠的PM中显着减弱,并且没有达到统计学显着性[2]。反复给予咯利普兰(1.25 mg/kg,ip)可减少学习无助大鼠的逃避失败次数[3]。

[细胞实验]

J774鼠巨噬细胞（ATCC）在37℃，5％CO2气氛下，在补充有含10％热灭活FBS，100U / mL青霉素，100μg/ mL链霉素和250ng / mL两性霉素B的glutamax-1的DMEM中培养。对于实验，将细胞以每孔2×10 5个细胞的密度接种在24孔板上。在开始实验之前，将细胞单层生长72小时。将Rolipram，IBMX和BIRB 796溶解在DMSO中，并将8-Br-cAMP溶解在HBSS中。将LPS（10ng / mL）或指定浓度的目标化合物或溶剂（DMSO，0.1％v / v）加入含有10％FBS和补充物的新鲜培养基中的细胞中。将细胞进一步温育指定的时间。通过细胞增殖试剂盒II（XTT）[2]评估LPS和测试的化学物质对细胞活力的影响。

[动物实验]

使用小鼠[2]近交系C57BL / 6 MKP-1（ - / - ）小鼠。将C57BL / 6小鼠（20-25g）分成6只小鼠的组，并在施用角叉菜胶之前2小时通过ip注射用200μLPBS或咯利普兰（PBS中100mg / kg）处理。在施用角叉菜胶之前，通过腹膜内注射0.5mg / kg美托咪定和75mg / kg氯胺酮麻醉小鼠。小鼠在一只后爪中接受30μLid注射角叉菜胶（1.5％，溶于生理盐水中）。对侧爪接受30μL盐水并将其用作对照。在用体积描记器注射角叉菜胶之前和之后3小时测量爪体积。水肿表示为爪子体积随时间的变化。

[参考文献]

[1]. MacKenzie SJ, et al. Action of rolipram on specific PDE4 cAMP phosphodiesterase isoforms and on the phosphorylation of cAMP-response-element-binding protein (CREB) and p38 mitogen-activated protein (MAP) kinase in U937 monocyticcells. Biochem J. 2000 Apr

[2]. Korhonen R, et al. Attenuation of TNF production and experimentally induced inflammation by PDE4 inhibitor rolipram is mediated by MAPK phosphatase-1. Br J Pharmacol. 2013 Aug;169(7):1525-36.

[3]. Shalaby AM, et al. Effect of rolipram, a phosphodiesterase enzyme type-4 inhibitor, on γ-amino butyric acid content of the frontal cortex in mice exposed to chronic mild stress. J Pharmacol Pharmacother. 2012 Apr;3(2):132-7.

[相关活性小分子]

咯利普兰物理化学性质

[ 密度 ]:
1.2±0.1 g/cm3

[ 沸点 ]:
472.7±45.0 °C at 760 mmHg

[ 熔点 ]:
127-133ºC

[ 分子式 ]:
C₁₆H₂₁NO₃

[ 分子量 ]:
275.343

[ 闪点 ]:
239.7±28.7 °C

[ 精确质量 ]:
275.152130

[ PSA ]:
47.56000

[ LogP ]:
1.43

[ 外观性状 ]:
固体

[ 蒸汽压 ]:
0.0±1.2 mmHg at 25°C

[ 折射率 ]:
1.552

[ 储存条件 ]:
0-6°C

[ 水溶解性 ]:
H2O: 0.2 mg/mL

咯利普兰MSDS

详细MSDS(安全技术说明书)

咯利普兰毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: UY5749237

CHEMICAL NAME :: 2-Pyrrolidinone, 4-(3-(cyclopentyloxy)-4-methoxyphenyl)-

CAS REGISTRY NUMBER :: 61413-54-5

LAST UPDATED :: 199806

DATA ITEMS CITED :: 5

MOLECULAR FORMULA :: C16-H21-N-O3

MOLECULAR WEIGHT :: 275.38

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >300 mg/kg

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

REFERENCE :: BPBLEO Biological and Pharmaceutical Bulletin. (Pharmaceutical Society of Japan, 2-12-15-201 Shibuya Shibuya-ku, Tokyo 150, Japan) V.16- 1993- Volume(issue)/page/year: 17,498,1994 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1400 mg/kg/14D-I

TOXIC EFFECTS :: Cardiac - other changes Gastrointestinal - changes in structure or function of salivary glands Liver - hepatitis (hepatocellular necrosis), zonal

REFERENCE :: PHTOEH Pharmacology and Toxicology (Copenhagen). (Munksgaard International Pub., POB 2148, DK-1016 Copenhagen K, Denmark) V.60- 1987- Volume(issue)/page/year: 78,44,1996

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 364 mg/kg/26W-I

TOXIC EFFECTS :: Kidney, Ureter, Bladder - urine volume increased Blood - pigmented or nucleated red blood cells Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 31,1465,1997

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 910 mg/kg/26W-I

TOXIC EFFECTS :: Gastrointestinal - changes in structure or function of salivary glands Gastrointestinal - nausea or vomiting

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 31,1527,1997

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 448 mg/kg/4W-I

TOXIC EFFECTS :: Behavioral - coma Gastrointestinal - nausea or vomiting Related to Chronic Data - death

REFERENCE :: KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 31,1491,1997

咯利普兰安全信息

[ 个人防护装备 ]:
dust mask type N95 (US);Eyeshields;Gloves

[ 危害码 (欧洲) ]:
Xi

[ 风险声明 (欧洲) ]:
R36/37/38

[ 安全声明 (欧洲) ]:
26-36

[ 危险品运输编码 ]:
UN 3249

[ WGK德国 ]:
3

[ RTECS号 ]:
UY5749237

[ 包装等级 ]:
III

[ 危险类别 ]:
6.1(b)

[ 海关编码 ]:
2933790090

咯利普兰合成路线

详细合成路线

咯利普兰上下游产品

咯利普兰上游产品

咯利普兰下游产品

咯利普兰海关

[ 海关编码 ]: 2933790090

[ 中文概述 ]:
2933790090 其他内酰胺. 增值税率:17.0% 退税率:9.0% 监管条件:无最惠国关税:9.0% 普通关税:20.0%

[ 申报要素 ]: 品名, 成分含量, 用途, 乌洛托品请注明外观, 6－己内酰胺请注明外观, 签约日期

[ Summary ]:
2933790090. other lactams. VAT:17.0%. Tax rebate rate:9.0%. . MFN tariff:9.0%. General tariff:20.0%

咯利普兰文献

Phosphorylation of ezrin on Thr567 is required for the synergistic activation of cell spreading by EPAC1 and protein kinase A in HEK293T cells.

Biochim. Biophys. Acta 1853 , 1749-58, (2015)

Recent studies have demonstrated that the actin binding protein, ezrin, and the cAMP-sensor, EPAC1, cooperate to induce cell spreading in response to elevations in intracellular cAMP. To investigate t...

Sphingosine-1-phosphate lyase downregulation promotes colon carcinogenesis through STAT3-activated microRNAs.

J. Clin. Invest. 124(12) , 5368-84, (2014)

Growing evidence supports a link between inflammation and cancer; however, mediators of the transition between inflammation and carcinogenesis remain incompletely understood. Sphingosine-1-phosphate (...

Integrated analysis of transcriptomes of cancer cell lines and patient samples reveals STK11/LKB1-driven regulation of cAMP phosphodiesterase-4D.

Mol. Cancer Ther. 13(10) , 2463-73, (2014)

The recent proliferation of data on large collections of well-characterized cancer cell lines linked to therapeutic drug responses has made it possible to identify lineage- and mutation-specific trans...

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