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27007-85-8

27007-85-8结构式

常用中文名：螺氯马嗪
常用英文名：1-Thia-4,8-diazaspiro[4.5]decan-3-one,8-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-, hydrochloride (1:1)
CAS号：27007-85-8
分子式：C₂₂H₂₅Cl₂N₃OS₂
分子量：482.48900
相关类别：信号通路 G 蛋白偶联受体/G 蛋白拉斯
发布时间：2017-11-18 20:42:02
更新时间：2024-01-08 18:53:34
盐酸斯皮洛马嗪(APY-606)是一种抗精神病药和抗肿瘤药。盐酸斯皮洛马嗪抑制KRas。盐酸史匹克霉嗪诱导癌症细胞凋亡[1][2]。

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中文名	螺氯马嗪
英文名	8-[3-(2-chlorophenothiazin-10-yl)propyl]-1-thia-4,8-diazaspiro[4.5]decan-3-one,hydrochloride
英文别名	Disepron APY-606 Clospirazine hydrochloride Spiclomazine hydrochloride Spiclomazine Diceplon 1-Thia-4,8-diazaspiro(4.5)decan-3-one,8-(3-(2-chlorophenothiazin-10-yl)propyl)-,hydrochloride 8-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-1-thia-4,8-diazaspiro[4.5]decan-3-one hydrochloride

描述	盐酸斯皮洛马嗪(APY-606)是一种抗精神病药和抗肿瘤药。盐酸斯皮洛马嗪抑制KRas。盐酸史匹克霉嗪诱导癌症细胞凋亡[1][2]。
相关类别	研究领域 >> 癌症信号通路 >> G 蛋白偶联受体/G 蛋白 >> 拉斯研究领域 >> 神经疾病
靶点	K-RAS
体外研究	盐酸斯皮洛马嗪(0-100μg/mL；24和48小时)以剂量依赖的方式抑制胰腺癌细胞的非接触集落形成[1]。盐酸斯皮洛嗪(0.5x和1x IC50；48小时)通过线粒体途径诱导 CFPAC-1型和迈阿密PaCa-2细胞凋亡,显著提高细胞内放射性同位素水平[1]。盐酸斯皮洛马嗪(30μg/mL；24小时)抑制 CFPAC-1型和迈阿密PaCa-2细胞的细胞运动性[1]。盐酸斯皮洛马嗪(10和20μg/mL；24小时)在第2组期时阻滞癌细胞周期进展[2]。细胞活力测定[1]细胞系：CFPAC-1、MIA PaCa-2、HEK-293和HL-7702细胞浓度：0-100μg/mL培养时间：24和48小时结果：导致CFPAC-1和MIA PaCa-2细胞的生长时间和剂量依赖性减少。对正常HEK-293和HL-7702细胞的细胞毒性较小。CFPAC-1治疗48小时的IC50为15.2±2.0μg/mL(31.5±2.0μM),MIA PaCa-2为12.9±0.9μg/mL,HEK-293为41.9±1.4μg/mL和HL-7702为71.2±3.3μg/mL。细胞凋亡分析[1]细胞系：CFPAC-1和MIA PaCa-2细胞浓度：CFPAC1为7.6和15.2μg/mL,MIA PaCa-2为6.45和12.9μg/mL培养时间：48小时结果：早期凋亡细胞增加。Western Blot分析[1]细胞系：CFPAC-1和MIA PaCa-2细胞浓度：10、20和30μg/mL培养时间：24小时结果：caspase-3/9的裂解以剂量依赖的方式增加。Bax表达上调,Bcl-2蛋白表达减弱。胞浆中细胞色素c水平升高,线粒体中细胞色素c水平降低。细胞迁移试验[1]细胞系：CFPAC-1和MIA PaCa-2细胞浓度：30μg/mL培养时间：24小时结果：显著抑制两种胰腺癌细胞的迁移。细胞侵袭试验[1]细胞系：CFPAC-1和MIA PaCa-2细胞浓度：30μg/mL培养时间：24小时结果：通过下调MMP-2/9的表达抑制侵袭。细胞周期分析[2]细胞株：MIA-PaCa-2、CFPAC-1、BxPC-3、Capan-1和SW1990细胞浓度：10和20μg/mL培养时间：24小时结果：促进了MIA-PaCa-2、CFPAC-1和BxPC-2细胞株G2期或Capan-1与SW1990细胞系S期的癌症细胞周期阻滞。
体内研究	盐酸斯皮洛马嗪(68 mg/kg；静脉注射；两周内每隔一天)降低小鼠迈阿密PaCa-2异种移植肿瘤的生长[2]。动物模型：BALB/c小鼠,MIA PaCa-2异种移植模型[2]剂量：68 mg/kg给药：腹膜内注射,每隔一天,持续两周结果：完全阻断了五只小鼠中的三只的肿瘤生长。
参考文献	[1]. Zhao W, et al. Spiclomazine induces apoptosis associated with the suppression of cell viability, migration and invasion in pancreatic carcinoma cells. PLoS One. 2013 Jun 20;8(6):e66362. [2]. Guo X, et al. Spiclomazine displays a preferential anti-tumor activity in mutant KRas-driven pancreatic cancer. Oncotarget. 2018 Jan 8;9(6):6938-6951.

密度	1.42g/cm3
沸点	695.3ºC at 760mmHg
分子式	C₂₂H₂₅Cl₂N₃OS₂
分子量	482.48900
闪点	374.3ºC
精确质量	481.08200
PSA	86.18000
LogP	6.12160
蒸汽压	3.51E-19mmHg at 25°C

CHEMICAL IDENTIFICATION

RTECS NUMBER :: XI2277500

CHEMICAL NAME :: 1-Thia-4,8-diazaspiro(4.5)decan-3-one, 8-(3-(2-chlorophenothiazin-10-yl)propyl)-, hydrochloride

CAS REGISTRY NUMBER :: 27007-85-8

LAST UPDATED :: 199203

DATA ITEMS CITED :: 11

MOLECULAR FORMULA :: C22-H24-Cl-N3-O-S2.Cl-H

MOLECULAR WEIGHT :: 482.52

WISWESSER LINE NOTATION :: T C666 BN ISJ EG B3- AT6N DXTJ D-& BT5SXMV EHJ &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3800 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - changes in REM sleep (human) Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,487,1970

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2950 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - changes in REM sleep (human) Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,487,1970

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >5490 mg/kg

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

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,487,1970

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 3800 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - changes in REM sleep (human) Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,487,1970

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 3200 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - changes in REM sleep (human) Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,487,1970

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >5490 mg/kg

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

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,487,1970 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 60 mg/kg

SEX/DURATION :: female 9-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - live birth index (measured after birth)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,497,1970

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 300 mg/kg

SEX/DURATION :: female 9-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,497,1970

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 60 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) Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,497,1970

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 240 mg/kg

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

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,497,1970

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 600 mg/kg

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

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 4,497,1970