匹莫齐特_MSDS_用途_密度_匹莫齐特CAS号【2062-78-4】

Pimozide 是 dopamine receptor 的拮抗剂,对 dopamine D2,D3 和 D1 受体的 Ki 值分别为 1.4 nM,2.5 nM 和 588 nM,同时对 α1-adrenoceptor 也有较高亲和性,Ki 值为 39 nM；Pimozide 也是 STAT3 和 STAT5 的抑制剂。

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[ 描述 ]:

Pimozide 是 dopamine receptor 的拮抗剂,对 dopamine D2,D3 和 D1 受体的 Ki 值分别为 1.4 nM,2.5 nM 和 588 nM,同时对 α1-adrenoceptor 也有较高亲和性,Ki 值为 39 nM；Pimozide 也是 STAT3 和 STAT5 的抑制剂。

[ 相关类别 ]:

信号通路 >> G 蛋白偶联受体/G 蛋白 >> 肾上腺素能受体

信号通路 >> G 蛋白偶联受体/G 蛋白 >> 多巴胺受体

信号通路 >> 神经信号通路 >> 多巴胺受体

信号通路 >> JAK/STAT信号通路 >> STAT

信号通路 >> 干细胞及 Wnt 通路 >> STAT

研究领域 >> 癌症

研究领域 >> 神经疾病

[ 靶点 ]

Dopamine D2 receptor:1.4 nM (Ki)

Dopamine D3 receptor:2.5 nM (Ki)

Dopamine D1 receptor:588 nM (Ki)

α1-adrenoceptor:39 nM (Ki)

STAT3

STAT5

[体外研究]

Pimozide是一种多巴胺受体拮抗剂,对于多巴胺D2,D3和D1受体,Kis分别为1.4 nM,2.5 nM和588 nM;对α1-肾上腺素能受体和5-HT1A也具有亲和力,Kis分别为39 nM和310 nM [1]。 Pimozide充当STAT3的抑制剂。匹莫齐特(0-15μM)显示出对U2OS细胞增殖的抑制,在24,48和72小时的IC50值分别为22.16±2.54,17.49±1.14和13.78±0.34μM。匹莫齐特(10μM)抑制骨肉瘤细胞的集落和球形成能力。 Pimozide(15μM)诱导G0/G1期细胞周期停滞,抑制细胞外信号调节激酶(Erk)信号通路抑制细胞活力,并通过抑制骨肉瘤细胞中抗氧化酶基因过氧化氢酶的表达产生ROS [2]。 Pimozide充当STAT5的抑制剂。 Pimozide降低内源性STAT5靶基因的表达,并降低STAT5酪氨酸磷酸化[3]。

[细胞实验]

通过WST-8比色测定评估细胞增殖。将人骨肉瘤细胞接种在96孔板中，每孔2,500个细胞，并暴露于不同浓度的匹莫齐特处理不同的时间间隔（24小时，48小时和72小时）。在指定时间后将WST-8溶液添加到每个孔中。在37℃下再培养4小时后，使用多孔板读数器在450nm处测量吸光度[2]。

[参考文献]

[1]. Ybema CE, et al. Adrenoceptors and dopamine receptors are not involved in the discriminative stimulus effect of the 5-HT1A receptor agonist flesinoxan. Eur J Pharmacol. 1994 Apr 21;256(2):141-7.

[2]. Cai N, et al. The STAT3 inhibitor pimozide impedes cell proliferation and induces ROS generation in human osteosarcoma by suppressing catalase expression. Am J Transl Res. 2017 Aug 15;9(8):3853-3866. eCollection 2017.

[3]. Erik A. Nelson, et al. The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors. Blood. 2011 Mar 24; 117(12): 3421-3429.

[相关活性小分子]

[ 密度 ]:
1.2±0.1 g/cm3

[ 沸点 ]:
649.0±65.0 °C at 760 mmHg

[ 分子式 ]:
C₂₈H₂₉F₂N₃O

[ 分子量 ]:
461.546

[ 闪点 ]:
346.3±34.3 °C

[ 精确质量 ]:
461.227875

[ PSA ]:
41.03000

[ LogP ]:
6.06

[ 蒸汽压 ]:
0.0±2.0 mmHg at 25°C

[ 折射率 ]:
1.623

[ 储存条件 ]:
2-8°C

[ 水溶解性 ]:
DMSO: 18 mg/mL

详细MSDS(安全技术说明书)

CHEMICAL IDENTIFICATION

RTECS NUMBER :: DE1750000

CHEMICAL NAME :: 2-Benzimidazolinone, 1-(1-(4,4-bis(p-fluorophenyl)butyl)-4-piperidyl)-

CAS REGISTRY NUMBER :: 2062-78-4

BEILSTEIN REFERENCE NO. :: 0729089

LAST UPDATED :: 199612

DATA ITEMS CITED :: 22

MOLECULAR FORMULA :: C28-H29-F2-N3-O

MOLECULAR WEIGHT :: 461.60

WISWESSER LINE NOTATION :: T56 BMVNJ D- DT6NTJ A3YR DF&R DF

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 7714 ug/kg/15W-I

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - fluid intake Kidney, Ureter, Bladder - urine volume increased

REFERENCE :: JCPYDR Journal of Clinical Pyschopharmacology. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1981- Volume(issue)/page/year: 12,140,1992

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1100 mg/kg

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

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,639,1982

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 350 mg/kg

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

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,639,1982

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >11 gm/kg

TOXIC EFFECTS :: Brain and Coverings - recordings from specific areas of CNS Sense Organs and Special Senses (Eye) - ptosis 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: 6,629,1972

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 90 mg/kg

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

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 5,106,1974

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 228 mg/kg

TOXIC EFFECTS :: Behavioral - ataxia

REFERENCE :: CCCCAK Collection of Czechoslovak Chemical Communications. (Academic Press Inc. Ltd., 24-28 Oval Rd., London NW1 7DX, UK) V.1- 1929- Volume(issue)/page/year: 42,1179,1977

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1070 mg/kg

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

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 5,106,1974

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >16 gm/kg

TOXIC EFFECTS :: Brain and Coverings - recordings from specific areas of CNS Sense Organs and Special Senses (Eye) - ptosis 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: 6,629,1972

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 14 mg/kg

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

REFERENCE :: 27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,288,1972

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 40 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 18,261,1968

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 32 mg/kg

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

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 5,106,1974

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 40 mg/kg

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

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 5,106,1974

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 22 mg/kg

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

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 5,106,1974

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 189 mg/kg

TOXIC EFFECTS :: Behavioral - tremor Behavioral - convulsions or effect on seizure threshold

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 18,261,1968 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 6500 mg/kg/30D-I

TOXIC EFFECTS :: Behavioral - muscle weakness Endocrine - hypoglycemia 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: 6,629,1972

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 624 mg/kg/26W-I

TOXIC EFFECTS :: 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: 6,629,1972 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1664 mg/kg

SEX/DURATION :: female 26 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - breasts, lactation (prior to or during pregnancy)

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: 6,629,1972

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 39 mg/kg

SEX/DURATION :: female 22 week(s) pre-mating

TOXIC EFFECTS :: Reproductive - Maternal Effects - uterus, cervix, vagina

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: 6,629,1972

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 49 mg/kg

SEX/DURATION :: male 2 week(s) pre-mating female 2 week(s) pre-mating female 21 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced 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: 14,2163,1980

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 80 ug/kg

SEX/DURATION :: male 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - other effects on male Endocrine - differential effect of sex or castration on observed toxicity

REFERENCE :: PBBHAU Pharmacology, Biochemistry and Behavior. (ANKHO International Inc., P.O. Box 426, Fayetteville, NY 13066) V.1- 1973- Volume(issue)/page/year: 46,697,1993

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 24 mg/kg

SEX/DURATION :: female 7-12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

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: 6,629,1972

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

DOSE :: 375 ug/kg

SEX/DURATION :: female 6-10 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - parturition

REFERENCE :: BIREBV Biology of Reproduction. (Soc. for the Study of Reproduction, 309 W. Clark St., Champaign, IL 61820) V.1- 1969- Volume(issue)/page/year: 29,658,1983

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[ 符号 ]:

GHS07

[ 信号词 ]:
Warning

[ 危害声明 ]:
H302

[ 警示性声明 ]:
P301 + P312 + P330

[ 危害码 (欧洲) ]:
Xn: Harmful;

[ 风险声明 (欧洲) ]:
R22

[ 安全声明 (欧洲) ]:
S36

[ 危险品运输编码 ]:
3249

[ WGK德国 ]:
3

[ RTECS号 ]:
DE1750000

[ 包装等级 ]:
III

[ 危险类别 ]:
6.1(b)

[ 海关编码 ]:
2933990090

详细合成路线

匹莫齐特上游产品

匹莫齐特下游产品

[ 海关编码 ]: 2933990090

[ 中文概述 ]:
2933990090. 其他仅含氮杂原子的杂环化合物. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 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 ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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J. Phys. Chem. B 118(33) , 9974-82, (2014)

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