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环孢菌素

环孢菌素用途

Cyclosporin A 是一种免疫抑制剂,能与亲环素结合,抑制 calcineurin 活性的IC50 值为 7 nM。
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环孢菌素名称

[ CAS 号 ]:
59865-13-3

[ 中文名 ]:
环孢菌素

[ 英文名 ]:
Cyclosporin A

[中文别名 ]:

[英文别名 ]:

环孢菌素生物活性

[ 描述 ]:

Cyclosporin A 是一种免疫抑制剂,能与亲环素结合,抑制 calcineurin 活性的IC50 值为 7 nM。

[ 相关类别 ]:

信号通路 >> 其他 >> 其他
研究领域 >> 炎症/免疫

[ 靶点 ]

IC50: 7 nM (calcineurin)


[体外研究]

环孢菌素A能够与T细胞中的亲环蛋白结合[1]。环孢菌素A通过形成亲环蛋白 - 环孢菌素A复合物来抑制神经钙蛋白[2]。环孢菌素A对钙调神经磷酸酶具有抑制作用,IC50为7 nM [3]。环孢菌素A抑制NF-AT的核转位[4]。环孢菌素A通过阻止MTP打开显示对线粒体的影响,IC50为39 nM [5]。

[体内研究]

环孢菌素A具有免疫抑制活性,并且在小鼠,大鼠和豚鼠中通过肠胃外和口服给药具有活性[6]。环孢菌素A可用于器官移植以防止排斥反应[7]。

[溶解度]

体外:

DMSO:62.5 mg / mL(51.97 mM;需要超声波)

H 2 O:<0.1 mg / mL(不溶)

体内:1。逐个添加每种溶剂:10%DMSO 90%玉米油溶解度:≥2.08mg / mL(1.73 mM);澄清溶液2.逐个添加每种溶剂:10%DMSO 40%PEG300 5%吐温-80 45%盐水溶解度:2.08mg / mL(1.73mM);暂停解决方案;需要超声波

[储备液]

1 mM 0.8315 mL 4.1576 mL 8.3152 mL
5 mM 0.1663 mL 0.8315 mL 1.6630 mL
10 mM 0.0832 mL 0.4158 mL 0.8315 mL

[激酶实验]

与纯化酶的反应混合物含有100 nM钙调神经磷酸酶,100 nM钙调蛋白和5μM32P标记的磷酸肽,在60μL(总体积)的含有20 mM Tris(pH 8),100 mM NaCl,6 mM MgCl 2,0.5的分析缓冲液中mM二硫苏糖醇,每毫升0.1mg牛血清白蛋白,和0.1mM CaCl 2或5mM EGTA。与细胞裂解物的反应混合物含有20μL未稀释的裂解物,5μM32P标记的磷酸肽和40μL测定缓冲液。反应混合物含有50μM肽412或413和/或500nM冈田酸,磷酸酶1和2A的特异性抑制剂; 500nM冈田酸足以抑制Ca2 +非依赖性磷酸酶,而较高浓度也部分抑制Ca2 +依赖性磷酸酶活性。在30℃下15分钟后,通过加入0.5mL含有5%三氯乙酸的100mM磷酸钾缓冲液(pH7.0)终止反应。通过Dowex阳离子交换色谱法分离游离无机磷酸盐,并如所述通过闪烁计数进行定量。

[细胞实验]

免疫抑制剂以比细胞处理所需浓度高1000倍的浓度溶解在乙醇中。将细胞(106)悬浮于微量离心管中的1mL完全培养基中;加入1μL乙醇或环孢菌素A的乙醇溶液,并将细胞在37℃下孵育1小时。将细胞在冰上用1mL PBS洗涤两次,并在含有50mM Tris(pH 7.5)的50μL低渗缓冲液中裂解; 0.1mM EGTA; 1 mM EDTA; 0.5mM二硫苏糖醇;每毫升50μg苯甲基磺酰氟,50μg大豆胰蛋白酶抑制剂,5μg亮肽素和5μg抑肽酶。将裂解物在液氮中进行三个循环的冷冻,然后在30℃下解冻,然后在4℃下以12,000×g离心10分钟。

[动物实验]

在第0天腹膜内用0 5mL免疫大鼠,小鼠静脉内用0 2mL 10%洗过的绵羊红细胞(SE)悬浮液免疫。为了引起二次反应,在初次免疫后8-11周,用静脉内注射0-2mL的25%洗涤的SE(107个细胞)对小鼠进行加强免疫。对于长期治疗,动物在13周内每天在食物中平均接受45mg / kg环孢菌素A.在杀死前5天对这些大鼠进行免疫。

[存储]

4°C,避光


[运输]

室温;可能会有所不同

[SMILES]

O[C@@H]([C@](C(N[C@H](C(N(CC(N([C@H](C(N[C@@](C(N([C@H]1CC(C)C)C)=O)([H])C(C)C)=O)CC(C)C)C)=O)C)=O)CC)=O)([H])N(C([C@](N(C([C@@H](N(C([C@H](N(C([C@H](NC([C@@H](NC1=O)C)=O)C)=O)C)CC(C)C)=O)C)CC(C)C)=O)C)([H])C(C)C)=O)C)[C@H](C)C/C=C/C

[参考文献]

[1]. Handschumacher RE, et al. Cyclophilin: a specific cytosolic binding protein for cyclosporin A. Science. 1984 Nov 2;226(4674):544-7.

[2]. Liu J, et al. Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. Cell. 1991 Aug 23;66(4):807-15.

[3]. Fruman DA, et al. Calcineurin phosphatase activity in T lymphocytes is inhibited by FK 506 and cyclosporin A. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3686-90.

[4]. Flanagan WM, et al. Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A. Nature. 1991 Aug 29;352(6338):803-7.

[5]. Nicolli A, et al. Interactions of cyclophilin with the mitochondrial inner membrane and regulation of the permeability transition pore, and cyclosporin A-sensitive channel. J Biol Chem. 1996 Jan 26;271(4):2185-92.

[6]. Borel JF, et al. Effects of the new anti-lymphocytic peptide cyclosporin A in animals. Immunology. 1977 Jun;32(6):1017-25.

[7]. Williams, R, et al. Randomised trial comparing tacrolimus (FK506) and cyclosporin in prevention of liver allograft rejection. European FK506 Multicentre Liver Study Group. Lancet, 1994, 344(8920), 423-428.


[相关活性小分子]

磺丁基-β-环糊精 | 2',7'-二氯荧光素二乙酸酯 | 1-甲基-4-苯基-1,2,3,6-四氢吡啶盐酸盐 | 4',4''-双-2-咪唑啉-2-基对苯二丙烯酰苯胺二盐酸盐 | 乙莫克舍 | TD139 | Mitoquinone甲磺酸盐 | GSK2795039 | JC-1 | 胞内钙荧光探针 BAPTA-AM | AP20187 | GKT137831 | D-荧光素 | 野百合碱 | BPTES

[相关文档]

*以上文档由Medchemexpress提供,仅用于科学研究参考。

环孢菌素物理化学性质

[ 密度 ]:
1.0±0.1 g/cm3

[ 沸点 ]:
1293.8±65.0 °C at 760 mmHg

[ 熔点 ]:
148-151°C

[ 分子式 ]:
C62H111N11O12

[ 分子量 ]:
1202.611

[ 闪点 ]:
736.3±34.3 °C

[ 精确质量 ]:
1201.841309

[ PSA ]:
278.80000

[ LogP ]:
3.35

[ 外观性状 ]:
从-15℃的丙酮得白色针状结晶,熔点148~151℃,[α]D20-244°(C=0.6,氯仿)。溶于甲醇、乙醇、丙酮、乙醚或氯仿,微溶于水及饱和碳氢化合物。急性毒性LD50小鼠,大鼠,兔子(mg/kg):107,25,>10静脉注射;2329,1480,>1000口服。

[ 蒸汽压 ]:
0.0±0.6 mmHg at 25°C

[ 折射率 ]:
1.468

[ 储存条件 ]:
2-8°C

[ 水溶解性 ]:
ethanol: 30 mg/mL

环孢菌素MSDS

环孢菌素毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :
GZ4120000
CHEMICAL NAME :
Cyclosporin A
CAS REGISTRY NUMBER :
59865-13-3
LAST UPDATED :
199801
DATA ITEMS CITED :
35
MOLECULAR FORMULA :
C62-H111-N11-O12
MOLECULAR WEIGHT :
1202.84

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - woman
DOSE/DURATION :
1911 mg/kg/91W-I
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold Behavioral - coma Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - woman
DOSE/DURATION :
62500 ug/kg/5D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - other changes Nutritional and Gross Metabolic - body temperature increase
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - man
DOSE/DURATION :
20 mg/kg/2D-I
TOXIC EFFECTS :
Behavioral - headache Vascular - acute arterial occlusion Lungs, Thorax, or Respiration - cyanosis
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human
DOSE/DURATION :
12 mg/kg
TOXIC EFFECTS :
Vascular - BP elevation not characterized in autonomic section Endocrine - antidiuresis
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Unreported
SPECIES OBSERVED :
Human - man
DOSE/DURATION :
30 mg/kg/4D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis)
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
1480 mg/kg
TOXIC EFFECTS :
Behavioral - muscle contraction or spasticity Gastrointestinal - hypermotility, diarrhea Skin and Appendages - hair
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
147 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 - rat
DOSE/DURATION :
286 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 :
Intravenous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
24 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 :
Oral
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
2329 mg/kg
TOXIC EFFECTS :
Behavioral - muscle contraction or spasticity Gastrointestinal - hypermotility, diarrhea Skin and Appendages - hair
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
96 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 :
Oral
SPECIES OBSERVED :
Rodent - rabbit
DOSE/DURATION :
>1 gm/kg
TOXIC EFFECTS :
Behavioral - muscle contraction or spasticity Gastrointestinal - hypermotility, diarrhea Skin and Appendages - hair
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - rabbit
DOSE/DURATION :
10 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
140 mg/kg/14D-I
TOXIC EFFECTS :
Endocrine - changes in spleen weight Blood - changes in spleen
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
350 mg/kg/7D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - other changes in urine composition Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - multiple enzyme effects
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
800 mg/kg/10D-I
TOXIC EFFECTS :
Behavioral - food intake (animal) Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
420 mg/kg/28D-I
TOXIC EFFECTS :
Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Musculoskeletal - other changes
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
700 mg/kg/28D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis) Kidney, Ureter, Bladder - other changes in urine composition
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
210 mg/kg/14D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - renal function tests depressed Kidney, Ureter, Bladder - other changes in urine composition Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - other transferases
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
1200 mg/kg/40D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - other changes in urine composition Biochemical - Metabolism (Intermediary) - amino acids (including renal excretion) Biochemical - Metabolism (Intermediary) - Plasma proteins not involving coagulation
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
140 mg/kg/7D-I
TOXIC EFFECTS :
Vascular - BP elevation not characterized in autonomic section Vascular - regional or general arteriolar or venous dilation
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
60 mg/kg/3D-I
TOXIC EFFECTS :
Vascular - BP elevation not characterized in autonomic section Vascular - structural changes in vessels Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Human - man
DOSE/DURATION :
259 mg/kg/2W-C
TOXIC EFFECTS :
Tumorigenic - Carcinogenic by RTECS criteria Blood - lymphoma, including Hodgkin's disease
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
166 mg/kg
SEX/DURATION :
male 45 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - other effects on male Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
420 mg/kg
SEX/DURATION :
male 14 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Subcutaneous
DOSE :
560 mg/kg
SEX/DURATION :
male 14 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count) Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - other effects on male
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
90 mg/kg
SEX/DURATION :
female 6-8 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetal death
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intraperitoneal
DOSE :
50 mg/kg
SEX/DURATION :
female 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 - craniofacial (including nose and tongue)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intramuscular
DOSE :
210 mg/kg
SEX/DURATION :
female 14 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Fertility - other measures of fertility

MUTATION DATA

TYPE OF TEST :
Sister chromatid exchange
TEST SYSTEM :
Human Lymphocyte
DOSE/DURATION :
1 mg/L
REFERENCE :
IGAYAY Igaku No Ayumi. Progress in Medicine. (Ishiyaku Shuppan K.K., 1-7-10, Honkomagom, Bunkyo-ku, Tokyo, Japan) V.1- 1946- Volume(issue)/page/year: 134,403,1985 *** REVIEWS *** IARC Cancer Review:Human Sufficient Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 50,77,1990 IARC Cancer Review:Animal Limited Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 50,77,1990 IARC Cancer Review:Group 1 IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 50,77,1990
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环孢菌素安全信息

[ 符号 ]:

GHS07, GHS08

[ 信号词 ]:
Danger

[ 危害声明 ]:
H302-H350-H360

[ 警示性声明 ]:
P201-P301 + P312 + P330-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) ]:
R45;R60;R22

[ 安全声明 (欧洲) ]:
53-45-36/37-24/25-22

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

[ WGK德国 ]:
3

[ RTECS号 ]:
GZ4120000

[ 海关编码 ]:
2941909000

环孢菌素上下游产品

环孢菌素制备

【方法一】
以多孢木霉菌(Tolypocladium inflatum Cams)为生产菌株。75L罐内装50L种子培养基,接种5×109个孢子,Ph=5.4—4.3,培养72h,得到一级种子液。750L发酵罐内装500L发酵培养基,种入上述一级种子液,培养6天,得二级种子液。4500L发酵罐内装3000L发酵培养基,发酵12天,得到环孢素发酵毒。往发酵液中加人等体积的乙酸乙酯提取,分出有机层,减压蒸发,得粗品。融化处理,可得环孢素和环孢菌素C组分,其中环孢素的产量约为150~200mg/L环孢菌素C约为50~100mg/L。
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环孢菌素海关

[ 海关编码 ]: 2941909000

环孢菌素文献

Proteomic analysis in serum of rat hind-limb allograft tolerance induced by immunosuppressive therapy with adipose-derived stem cells.

Plast. Reconstr. Surg. 134(6) , 1213-23, (2014)

Adipose-derived stem cells combined with transient immunosuppression prolonged vascularized composite tissue allotransplant survival and induced immune tolerance in a rodent hind-limb model. The autho...

Differentiation between human ClC-2 and CFTR Cl- channels with pharmacological agents.

Am. J. Physiol. Cell Physiol. 307(5) , C479-92, (2014)

It has been difficult to separate/identify the roles of ClC-2 and CFTR in Cl(-) transport studies. Using pharmacological agents, we aimed to differentiate functionally between ClC-2 and CFTR Cl(-) cha...

The Ca²⁺-calmodulin-Ca²⁺/calmodulin-dependent protein kinase II signaling pathway is involved in oxidative stress-induced mitochondrial permeability transition and apoptosis in isolated rat hepatocytes.

Arch. Toxicol. 88(9) , 1695-709, (2014)

Oxidative stress (OS) is a common event in most hepatopathies, leading to mitochondrial permeability transition pore (MPTP) formation and further exacerbation of both OS from mitochondrial origin and ...


更多文献

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相关药品:

推荐生产厂家/供应商:

公司名:宝鸡市国康生物科技有限公司

区域:宝鸡市渭滨区

价格:
¥需询单/1kg

联系人:孙经理

产品详情:环孢菌素


公司名:上海吉至生化科技有限公司

区域:上海市奉贤区

价格:
¥158.0/250mg ¥458.0/1g ¥158.0/20mg

联系人:王晓燕

产品详情:环胞霉素A


公司名:上海皓元生物医药科技有限公司

区域:上海市浦东新区

价格:
¥750.0/200mg ¥520.0/100mg ¥1380.0/500mg

联系人:高小姐

产品详情:Cyclosporin A


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