(S)-(-)-沙利度胺

(S)-(-)-沙利度胺用途

(S)-Thalidomide ((S)-(-)-Thalidomide) 是 Thalidomide 的 S-对映体。(S)-Thalidomide 具有免疫调节,抗炎,抗血管生成和促凋亡作用。(S)-Thalidomide 通过与 cereblon (CRBN) 结合诱导致畸作用。

(S)-(-)-沙利度胺名称

[ CAS 号 ]:
841-67-8

[ 中文名 ]:
(-)-沙利度胺

[ 英文名 ]:
(S)-Thalidomide

[中文别名 ]:

[英文别名 ]:

(-)-N-[(S)-2,6-Dioxo-3-piperidinyl]phthalimide
(-)-Thalidomide
6-dioxo-3-piperidyl)-n-(l-(-)-phthalimid
INHIBITOR OF ANGIOG EN
L-thalidomide
MFCD00210219

(S)-(-)-沙利度胺生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> 细胞凋亡 >> 细胞凋亡

研究领域 >> 炎症/免疫

研究领域 >> 代谢疾病

[ 靶点 ]

Apoptosis[1]

[体外研究]

(S) -沙利度胺治疗导致IC50为362μM的U266细胞活性降低[1]。(S) -沙利度胺治疗以剂量依赖的方式增加U266细胞的凋亡[1]。参与血管生成和凋亡的基因表达谱发生了变化,而凋亡基因的变化最为显著。尤其是,I-κB激酶的表达降低了两倍,这与NF-κB表达降低了四倍有关。(S) -沙利度胺增加Bax:Bcl-2比值,也增加I-kB蛋白水平,降低NF-kB活性。与(S)-沙利度胺相比,Bcl-2表达显著下降,提示与其他细胞毒性药物联合使用可增强细胞毒性作用〔1〕。细胞活力测定[1]细胞系：U266 M M细胞浓度：0μM、10μM、100μM、150μM、200μM、1000μM培养时间：3天结果：U266细胞活力下降。凋亡分析[1]细胞株：U266 M M细胞浓度：100μM、150μM、200μM、1000μM培养时间：3天结果：U266细胞凋亡增加。

[体内研究]

只要胚胎直接接触药物,沙利度胺确实会导致鸡胚的肢体缩小缺陷。最有用的技术是将浸过沙利度胺的珠子植入紧邻肢体区域的胚胎中,或将假定的鸡肢体区域浸在沙利度胺中,然后将外植体移植到宿主胚胎细胞上。沙利度胺以剂量反应方式影响移植到宿主胚胎上的鸡肢。此外,(S)-沙利度胺比(R)-沙利度胺更具致畸性[1]。

[参考文献]

[1]. Liu WM, et al. s-thalidomide has a greater effect on apoptosis than angiogenesis in a multiple myeloma cell line. Hematol J. 2004;5(3):247-54.

[2]. Stephens TD. The effect of thalidomide in chicken embryos. Birth Defects Res A Clin Mol Teratol. 2009 Aug;85(8):725-31.

[3]. Murphy S, et al. Enantioselectivity of thalidomide serum and tissue concentrations in a rat glioma model and effects of combination treatment with cisplatin and BCNU. J Pharm Pharmacol. 2007 Jan;59(1):105-14.

[4]. Tokunaga E, et al. Understanding the Thalidomide Chirality in Biological Processes by the Self-disproportionation of Enantiomers. Sci Rep. 2018 Nov 20;8(1):17131.

(S)-(-)-沙利度胺物理化学性质

[ 密度 ]:
1.503g/cm3

[ 沸点 ]:
509.7ºC at 760 mmHg

[ 熔点 ]:
269-271ºC

[ 分子式 ]:
C₁₃H₁₀N₂O₄

[ 分子量 ]:
258.22900

[ 闪点 ]:
262.1ºC

[ 精确质量 ]:
258.06400

[ PSA ]:
83.55000

[ LogP ]:
0.35450

[ 外观性状 ]:
针状

[ 折射率 ]:
1.646

[ 储存条件 ]:
-20°C，密闭，干燥

(S)-(-)-沙利度胺MSDS

详细MSDS(安全技术说明书)

(S)-(-)-沙利度胺毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: TI4925050

CHEMICAL NAME :: Phthalimide, N-(2,6-dioxo-3-piperidyl)-, L-(-)-

CAS REGISTRY NUMBER :: 841-67-8

LAST UPDATED :: 199012

DATA ITEMS CITED :: 6

MOLECULAR FORMULA :: C13-H10-N2-O4

MOLECULAR WEIGHT :: 258.25

WISWESSER LINE NOTATION :: T56 BVNVJ C- DT6VMVTJ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 700 mg/kg

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

REFERENCE :: NATUAS Nature. (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736) V.1- 1869- Volume(issue)/page/year: 215,296,1967 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 100 mg/kg

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

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 29,1640,1979

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 12500 ug/kg

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

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 29,1640,1979

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

DOSE :: 50 mg/kg

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

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 29,1640,1979

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 900 mg/kg

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

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

REFERENCE :: NATUAS Nature. (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736) V.1- 1869- Volume(issue)/page/year: 215,296,1967 *** REVIEWS *** TOXICOLOGY REVIEW BCSTB5 Biochemical Society Transactions. (Biochemical Soc. Book Depot, POB 32, Commerce Way, Colchester, Essex CO2 8HP, UK) V.1- 1973- Volume(issue)/page/year: 2,695,1974

(S)-(-)-沙利度胺安全信息

[ 符号 ]:

GHS07, GHS08

[ 信号词 ]:
Danger

[ 危害声明 ]:
H302-H360

[ 警示性声明 ]:
P201-P308 + P313

[ 个人防护装备 ]:
Eyeshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges

[ 危害码 (欧洲) ]:
T: Toxic;

[ 风险声明 (欧洲) ]:
R61

[ 安全声明 (欧洲) ]:
53-36/37/39-45

[ 危险品运输编码 ]:
UN 2811 6.1/PG 2

[ RTECS号 ]:
TI4925050

[ 海关编码 ]:
2925190090

(S)-(-)-沙利度胺合成路线

详细合成路线

(S)-(-)-沙利度胺上下游产品

(S)-(-)-沙利度胺上游产品

(S)-(-)-沙利度胺下游产品

(S)-(-)-沙利度胺海关

[ 海关编码 ]: 2925190090

[ 中文概述 ]:
2925190090 其他酰亚胺及其衍生物盐. 增值税率:17.0% 退税率:9.0% 监管条件:无最惠国关税:6.5% 普通关税:30.0%

[ 申报要素 ]: 品名, 成分含量, 用途

[ Summary ]:
2925190090 other imides and their derivatives; salts thereof VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:30.0%

(S)-(-)-沙利度胺文献

Thalidomide is an inhibitor of angiogenesis.

Proc. Natl. Acad. Sci. U. S. A. 91 , 4082, (1994)

Thalidomide is a potent teratogen causing dysmelia (stunted limb growth) in humans. We have demonstrated that orally administered thalidomide is an inhibitor of angiogenesis induced by basic fibroblas...

Thalidomide inhibits the replication of human immunodeficiency virus type 1.

Proc. Natl. Acad. Sci. U. S. A. 90 , 5974-5878, (1993)

Thalidomide, a selective inhibitor of tumor necrosis factor alpha (TNF-alpha) synthesis, suppresses the activation of latent human immunodeficiency virus type 1 (HIV-1) in a monocytoid (U1) line. The ...

Thalidomide induces limb anomalies by PTEN stabilization, Akt suppression, and stimulation of caspase-dependent cell death.

Mol. Cell. Biol. 28(2) , 529-538, (2008)

Thalidomide, a drug used for the treatment of multiple myeloma and inflammatory diseases, is also a teratogen that causes birth defects, such as limb truncations and microphthalmia, in humans. Thalido...

更多文献