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25316-40-9 分子结构
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(8S,10S)-10-{[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy}-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-5,7,8,9,10,12-hexahydrotetracene-5,12-dione hydrochloride

ChemBase编号:72574
分子式:C27H30ClNO11
平均质量:579.9802
单一同位素质量:579.15073847
SMILES和InChIs

SMILES:
c1ccc2c(c1OC)C(=O)c1c(C2=O)c(c2c(c1O)[C@H](C[C@@](C2)(C(=O)CO)O)O[C@H]1C[C@@H]([C@@H]([C@@H](O1)C)O)N)O.Cl
Canonical SMILES:
OCC(=O)[C@@]1(O)C[C@H](O[C@H]2C[C@H](N)[C@@H]([C@@H](O2)C)O)c2c(C1)c(O)c1c(c2O)C(=O)c2c(C1=O)cccc2OC.Cl
InChI:
InChI=1S/C27H29NO11.ClH/c1-10-22(31)13(28)6-17(38-10)39-15-8-27(36,16(30)9-29)7-12-19(15)26(35)21-20(24(12)33)23(32)11-4-3-5-14(37-2)18(11)25(21)34;/h3-5,10,13,15,17,22,29,31,33,35-36H,6-9,28H2,1-2H3;1H/t10-,13-,15-,17-,22+,27-;/m0./s1
InChIKey:
MWWSFMDVAYGXBV-RUELKSSGSA-N

引用这个纪录

CBID:72574 http://www.chembase.cn/molecule-72574.html

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名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
(8S,10S)-10-{[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy}-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-5,7,8,9,10,12-hexahydrotetracene-5,12-dione hydrochloride
IUPAC传统名
doxorubicin hydrochloride
(8S,10S)-10-{[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy}-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-5,7,8,9,10,12-hexahydrotetracene-5,12-dione hydrochloride
别名
多柔比星® 盐酸盐
羟基柔红霉素 盐酸盐
阿霉素 盐酸盐
DOX
Hydroxydaunorubicin hydrochloride
Doxorubicin hydrochloride
Doxorubicin Hydrochloride
Rubex
Adriamycin
Adriamycin
CAS号
25316-40-9
EC号
246-818-3
MDL号
MFCD00077757
Beilstein号
4229251
PubChem SID
162037499
24868204
PubChem CID
443939

数据来源

数据来源

所有数据来源 商品来源 非商品来源
数据来源 数据ID
PubChem 443939 external link

理论计算性质

理论计算性质

JChem
Acid pKa 9.53088  质子受体 12 
质子供体 LogD (pH = 5.5) -1.4428744 
LogD (pH = 7.4) -0.27556196  Log P 0.91642165 
摩尔折射率 134.5937 cm3 极化性 52.692078 Å3
极化表面积 206.07 Å2 可自由旋转的化学键
里宾斯基五规则 false 

分子性质

分子性质

理化性质 安全信息 药理学性质 产品相关信息 生物活性(PubChem)
溶解度
DMSO expand 查看数据来源
DMSO: soluble expand 查看数据来源
ethanol: soluble expand 查看数据来源
H2O: soluble50 mg/mL, clear, orange to red expand 查看数据来源
methanol: soluble expand 查看数据来源
THF: soluble expand 查看数据来源
熔点
216 °C (dec.)(lit.) expand 查看数据来源
荧光
λex 470 nm; λem 585 nm in ethanol expand 查看数据来源
保存条件
-20°C expand 查看数据来源
RTECS编号
QI9295900 expand 查看数据来源
欧盟危险性物质标志
有毒(Toxic) 有毒(Toxic) (T) expand 查看数据来源
刺激性(Irritant) 刺激性(Irritant) (Xi) expand 查看数据来源
MSDS下载
下载链接 expand 查看数据来源
德国WGK号
3 expand 查看数据来源
危险公开号
45-22-36/38 expand 查看数据来源
安全公开号
53-45 expand 查看数据来源
GHS危险品标识
GHS07 expand 查看数据来源
GHS08 expand 查看数据来源
GHS警示词
Danger expand 查看数据来源
GHS危险声明
H302-H315-H319-H350 expand 查看数据来源
GHS警示性声明
P201-P305 + P351 + P338-P308 + P313 expand 查看数据来源
个人保护装置
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 expand 查看数据来源
保存温度
2-8°C expand 查看数据来源
作用靶点
Topoisomerase expand 查看数据来源
生物活性机理
Forms complexes with DNA by intercalation between base pairs expand 查看数据来源
Inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes expand 查看数据来源
May also inhibit polymerase activity, affect regulation of gene expression, and produce free radical damage to DNA expand 查看数据来源
纯度
98.0-102.0% (HPLC) expand 查看数据来源
成盐信息
HCL expand 查看数据来源
HCl expand 查看数据来源
适用性
suitable for fluorescence expand 查看数据来源
生物来源
Metab. of Streptomyces peucetius expand 查看数据来源
应用领域
Antineoplastic antibiotic expand 查看数据来源
Possesses an antitumor effect against a wide spectrum of tumors expand 查看数据来源
Shows anti-HIV activity expand 查看数据来源
Used in the treatment of ovarian cancer and AIDS related Kaposi sarcoma expand 查看数据来源
Empirical Formula (Hill Notation)
C27H29NO11 · HCl expand 查看数据来源

详细说明

详细说明

Selleck Chemicals Selleck Chemicals Sigma Aldrich Sigma Aldrich
Selleck Chemicals -  S1208 external link
Research Area
Description Cancer
Biological Activity
Description Doxorubicin (Adriamycin) is an antibiotic agent that inhibits DNA topoisomerase II and induces DNA damage and apoptosis.
Targets
IC50
In Vitro Doxorubicin, an antibiotic anthracycline, is commonly considered to exert its anti-tumor activity at two fundamental levels, altering DNA and producing free radicals to trigger apoptosis of cancer cells through DNA damage. Doxorubicin can block the synthesis of DNA by intercalating into the DNA strand, and inhibits DNA topoisomerase II (TOP2). Doxorubicin is most effective when cells are rapidly proliferating and expressing high levels of TOP2. Additionally, Doxorubicin can trigger apoptosis by producing ceramide (which prompts apoptosis by activating p53 or other downstream pathways such as JNK), the degradation of Akt by serine threonine proteases, the mitochondrial release of cytochrome c, increased FasL (death receptor Fas/CD95 ligand) mRNA production, and a greater production of free radicals. [2] Pre-treatment with GSNO (nitrosoglutathione) suppresses the resistance in the doxorubicin-resistant breast cancer cell line MCF7/Dx, accompanied by enhanced protein glutathionylation and accumulation of doxorubicin in the nucleus. [3] Doxorubicin induced G2/M checkpoint arrest are attributed to elevated cyclin G2 (CycG2) expression and phospho-modification of proteins in the ataxia telangiectasia mutated (ATM) and ATM and Rad3-related (ATR) signaling pathways. [5] Doxorubicin inhibits AMP-activated protein kinase (AMPK), resulting in SIRT1 dysfunction, p53 accumulation, and increased cell death in mouse embryonic fibroblasts (MEFs) and cardiomyocytes, which can be further sensitized by pre-inhibition of AMPK. [6] Doxorubicin elicits a marked heat shock response, and that either inhibition or silencing of heat shock proteins enhance the Doxorubicin apoptotic effect in neuroblastoma cells. Nanomolar Doxorubicin treatment of neuroblastoma cells causes dose-dependent over-ubiquitination of a specific set of proteins in the absence of measurable inhibition of proteasome, and loss of activity of ubiquitinated enzymes such as lactate dehydrogenase and α-enolase, the protein ubiquination patterns of which is similar to those with proteasome inhibitor Bortezomib, indicating that Doxorubicin may also exert its effect by damaging proteins. [8]
In Vivo Although its use is limited by the chronic and acute toxic side effects it produces, Doxorubicin is essential in treating breast and oesophageal carcinomas, solid tumours in childhood, osteosarcomas, Kaposi’s sarcoma, soft tissue sarcomas, and Hodgkin and non-Hodgkin lymphomas. [2] In vivo, Doxorubicin in combination with adenoviral MnSOD (AdMnSOD) plus 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) has the greatest effect in decreasing the volumes of MB231 tumors and prolonging survival of mice. [1]
Clinical Trials A Phase III study of Doxorubicin alone vs. Doxorubicin in combination with TH-302 in subjects with locally advanced unresectable or metastatic soft tissue sarcoma is currently ongoing.
Features
Combination Therapy
Description Doxorubicin in combination with sodium butyrate (an HDACi) potentiates apoptosis and synergistically reduces the viability of myeloma cells independent of p53 and caspase 3-7 activation, which is correlated with nuclear translocation of apoptosis-inducing factor and significantly increased activity of cytoplasmic cathepsin B. Doxorubicin in combination with clinically relevant concentration of butyrate or SAHA significantly reduces the survival of primary myeloma cells. [4] Flavopiridol potentiates doxorubicin efficacy in sarcoma cell lines. In vivo, Doxorubicin administered 1 hour prior to flavopiridol is more active than Doxorubicin alone. [7] A Phase III study of Doxorubicin and Bortezomib or Bortezomib monotherapy for the treatment of telapsed multiple myeloma is currently ongoing.
Protocol
Animal Study [1]
Animal Models Female athymic nude mice injected s.c. with MB231 cells
Formulation Dissolved in DMSO, and diluted in saline
Doses 3 mg/kg/day
Administration Delivered intratumorly
References
[1] Sun W, et al. Cancer Res, 2009, 69(10), 4294-4300.
[2] Granados-Principal S, et al. Food Chem Toxicol, 2010, 48(6), 1425-1438.
[3] de Luca A, et al. Biochem J, 2011, 440(2), 175-183.
[4] Cheriyath V, et al. Br J Cancer, 2011, 104(6), 957-967.
[5] Zimmermann M, et al. J Biol Chem, 2012, 287(27), 22838-22853.
[6] Wang S, et al. J Biol Chem, 2012, 287(11), 8001-8012.
Sigma Aldrich -  44583 external link
Frequently Asked Questions
Live Chat and Frequently Asked Questions are available for this Product.
Application
Do you have application information on this product that you would like to share?
Doxorubicin is used as an antitumour antibiotic, to induce apoptosis, and to induce cardiotoxicity in SK-N-MC cells 2,3.
Used to inhibit macromolecular biosynthsis.
Biochem/physiol Actions
Antitumour antibiotic. Effect of adriamycin® on heart mitochondrial DNA;4 Properties.5,6
Inhibitor of reverse transcriptase and RNA polymerase; immunosuppressive agent; intercalates in DNA.
Doxorubicin intercalates DNA and inhibits macromolecular biosynthesis. DNA replication is haulted due to the inhibition of topoisomerase II. It is an inhibitor of reverse transcriptase and RNA polymerase and is an immunosuppressive agent 1.
法律信息
Adriamycin 注册商标 RDF Pharmacia & Upjohn S.P.A.
Protocols & Applications
Antibiotic Selector for application, solubility, solution stability, working concentration, and mode of action information

参考文献

参考文献

供应商提供 Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
  • Wang S, et al. J Biol Chem, 2012, 287(11), 8001-8012.
  • Sun W, et al. Cancer Res, 2009, 69(10), 4294-4300.
  • Granados-Principal S, et al. Food Chem Toxicol, 2010, 48(6), 1425-1438.
  • de Luca A, et al. Biochem J, 2011, 440(2), 175-183.
  • Cheriyath V, et al. Br J Cancer, 2011, 104(6), 957-967.
  • Zimmermann M, et al. J Biol Chem, 2012, 287(27), 22838-22853.
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  • Lewis, R.J., Sax's Dangerous Properties of Industrial Materials, 8th edn., Van Nostrand Reinhold, 1992, AES750; EBB100; HKA300; COP765; DAM800
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