Doxorubicin (Adriamycin) 化学構造
分子量: 579.98

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製品説明

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    Topoisomerase製品生物活性の比較
  • 研究分野
  • Combination Therapy
    併用療法

製品の説明

生物活性

製品説明 Doxorubicin (Adriamycin) は、DNAトポイソメラーゼIIを妨げて、DNAの損傷とアポトーシスを誘発する抗生エージェントです。
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IC50
In vitro試験 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]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
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KU-19-19 MoXUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWrwV5hUUUN3ME2yMlI3QTF5IN88US=> NETVVmdUSU6JRWK=
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HCT-15 M{jW[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{TUdGlEPTB;Mj6zOVQ3PiEQvF2= NWi3RlB{W0GQR1XS
HuO-3N1 NYjofGpnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYnJR|UxRTJwM{[1PFMh|ryP M2[yTXNCVkeHUh?=
GMS-10 NG\EcpBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3nwTmlEPTB;Mj6zPVc{QCEQvF2= NVfTOZc2W0GQR1XS
TGBC24TKB NYC0c5R6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVXJR|UxRTJwNEG0Nlkh|ryP MmXqV2FPT0WU
C2BBe1 M4\5TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlfNTWM2OD1{LkWxN|I5KM7:TR?= NHzRbZVUSU6JRWK=
SK-N-DZ MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mlv1TWM2OD1{LkW2OVkzKM7:TR?= M3fnfHNCVkeHUh?=
SK-N-AS M4LmR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{XDUmlEPTB;Mj63N|AyPSEQvF2= MXPTRW5ITVJ?
T98G MnHSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{nJZmlEPTB;Mj64NFQxOSEQvF2= MmfZV2FPT0WU
DMS-79 NV72dmNDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlLwTWM2OD1{LkmwPVg5KM7:TR?= NVHJXY9OW0GQR1XS
SNU-475 MlrtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3\VPGlEPTB;Mj65NlU4OiEQvF2= M1yxdXNCVkeHUh?=
COLO-792 MlrKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX;JR|UxRTNwMEK4O{DPxE1? MW\TRW5ITVJ?
YAPC MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3vzZ2lEPTB;Mz6zNlg{OiEQvF2= M3z6eHNCVkeHUh?=
UACC-812 NUPRbI5mT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml62TWM2OD1|LkOzO|M5KM7:TR?= MW\TRW5ITVJ?
Mewo M{TQNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFnRSVlKSzVyPUOuOFYxQDZizszN M4\vOXNCVkeHUh?=
COLO-824 M{fWSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUPJR|UxRTNwNUezO|gh|ryP NXLhZ5c2W0GQR1XS
SCC-9 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoXuTWM2OD1|LkmxN|A6KM7:TR?= NF;ubY5USU6JRWK=
CP50-MEL-B NVH3SY5{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWjLfFI{UUN3ME2zMlk5PzB|IN88US=> NYHZTHlwW0GQR1XS
NCI-H345 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoPzTWM2OD12LkCxNVc1KM7:TR?= NUTLOoV6W0GQR1XS
COR-L88 M{\adGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2LtbGlEPTB;ND6zPVU5KM7:TR?= MkHMV2FPT0WU
RCM-1 Ml3oS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFzuT5JKSzVyPUSuOFkzPzJizszN MXLTRW5ITVJ?
JVM-3 NIjVd5NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXf6RXRLUUN3ME20MlYxPjF6IN88US=> MlHRV2FPT0WU
ECC4 M1[zS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoLwTWM2OD12Lke2OVQyKM7:TR?= NYPOelI6W0GQR1XS
MDA-MB-453 NXPne|hoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXjrfIpQUUN3ME20Mlg2OTN2IN88US=> M2XuXXNCVkeHUh?=
SK-N-FI NGfNR4VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2mwdWlEPTB;NT6yNlg4PyEQvF2= NVH4blcxW0GQR1XS
D-502MG MljYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{nkPWlEPTB;NT6yOFI3OiEQvF2= MVzTRW5ITVJ?
NCI-H2227 NWDJcVZHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXvWfFhzUUN3ME21MlM3OjNzIN88US=> NX3KZoxKW0GQR1XS
DMS-53 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NULRVFc6UUN3ME22MlE4OTB4IN88US=> NXX3SJdnW0GQR1XS
LB771-HNC M3m2Z2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXvJR|UxRTZwNE[4NFYh|ryP NEK2S2hUSU6JRWK=
BB49-HNC NY\EdGhOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUnJd3p6UUN3ME23MlQyPzlzIN88US=> MYHTRW5ITVJ?
MDA-MB-415 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlzhTWM2OD15LkW3N|A{KM7:TR?= Ml\qV2FPT0WU
TALL-1 MlfZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVnJR|UxRTdwOU[4PEDPxE1? NIOwelZUSU6JRWK=
HCC1395 M2\YSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYW2XoNSUUN3ME24MlE2OTJ{IN88US=> NGDrNWdUSU6JRWK=
EFE-184 MonOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUDJR|UxRThwM{eyNVYh|ryP NUPMPGhYW0GQR1XS
EC-GI-10 M4HUVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV3V[mpbUUN3ME24MlY5Pjh4IN88US=> NH3RbnJUSU6JRWK=
TT Mm\6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYLJR|UxRTlwME[5OlYh|ryP NWDJTZd6W0GQR1XS
U-2-OS M{PEe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlPqTWM2OD17LkixN|k{KM7:TR?= M4TacnNCVkeHUh?=
SHP-77 NGr4V3BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mk\TTWM2OD17LkmwNlkh|ryP MX7TRW5ITVJ?
HCC1143 NHjLbZFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlrRTWM2OD1zMD60O|k4KM7:TR?= M3\6RnNCVkeHUh?=
A498 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3PXTmlEPTB;MUiuNlk4PiEQvF2= M{S1e3NCVkeHUh?=
LS-513 NVXUUINGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXHJR|UxRTF6Lk[wPVMh|ryP MVfTRW5ITVJ?
K052 M3ixSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEn2PJRKSzVyPUKxMlQ1OThizszN NUPFUohpW0GQR1XS
SiHa MoXPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3\FTmlEPTB;MkOuN|M4OSEQvF2= NG[yOGVUSU6JRWK=
RCC10RGB MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYjJR|UxRTNyLkC2NVEh|ryP M4rQNXNCVkeHUh?=
NCI-SNU-16 NX\tPGx1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoL3TWM2OD1|MT6xPFM3KM7:TR?= MmfsV2FPT0WU
SNU-C1 NHe0OZBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUnJdnVtUUN3ME2zNk41OTd3IN88US=> MUPTRW5ITVJ?
C32 MkK2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mkf0TWM2OD1|Mj64O|Ih|ryP NFLobJJUSU6JRWK=
SW684 NWG3T|VvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml3PTWM2OD1|ND6xOVYyKM7:TR?= NIO2XIZUSU6JRWK=
SK-MEL-28 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{TrPGlEPTB;M{WuOVM4PyEQvF2= NHX3ZY5USU6JRWK=
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NCI-H720 M2GwZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkPBTWM2OD12MT65O|I3KM7:TR?= NUDBPVVJW0GQR1XS
P31-FUJ NEnDUW5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnfETWM2OD12ND6zNlg1KM7:TR?= MmGwV2FPT0WU
NCI-H524 NELiTJhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFvQWW9KSzVyPUS4MlgzPDhizszN NFPmS2xUSU6JRWK=

... Click to View More Cell Line Experimental Data

In vivo試験 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] 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]
臨床試験 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.
特集

プロトコル (参考用のみ)

動物実験: [1]

動物モデル Female athymic nude mice injected s.c. with MB231 cells
製剤 Dissolved in DMSO, and diluted in saline
投薬量 3 mg/kg/day
投与方法 Delivered intratumorly

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download Doxorubicin (Adriamycin) SDF
分子量 579.98
化学式

C27H29NO11.HCl

CAS No. 25316-40-9
保管 2年-20℃
6月-80℃in solvent
別名 NSC 123127
溶解度 (25°C) * In vitro DMSO 100 mg/mL warming (172.41 mM)
20 mg/mL (34.48 mM)
エタノール <1 mg/mL (<1 mM)
In vivo
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
化学名 (8S,10S)-10-((2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyl-tetrahydro-2H-pyran-2-yloxy)-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione hydrochloride

カスタマーフィードバック (6)


Click to enlarge
Rating
Source , , Sci Transl Med, 2015, 7(284): 284ra57 . Doxorubicin (Adriamycin) purchased from Selleck
Method Apoptotic Response Assay
Cell Lines MDA-MB-231 cells
Concentrations 10 mg/kg
Incubation Time 24 h
Results The apoptotic response inMDA-MB-231 (human triple-negative breast) tumors, as tested by the device, was significantly elevated to 17.5% from 7.4%by the addition of lapatinib to doxorubicin in reservoirs.

Click to enlarge
Rating
Source Cancer Res, 2014, 74, 298-308. Doxorubicin (Adriamycin) purchased from Selleck
Method MTT assay
Cell Lines H1299, A549, Hep3B, HT1080, HCT116, MCF7
Concentrations
Incubation Time 48 h
Results Hypoxic (1% O2 ) conditions for 48 hours. The IC50 value for cisplatin or doxorubicin significantly increased under hypoxia in H1299, A549, Hep3B, and HT1080, but did not in HCT116 and MCF7

Click to enlarge
Rating
Source J Biomed Mater Res Part A, 2012, 10.1002/jbm.a.34064. Doxorubicin (Adriamycin) purchased from Selleck
Method Release experiment
Cell Lines N.A.
Concentrations 0.25mg/mL
Incubation Time 2-10 h
Results Doxorubicin was loaded by equilibrium partitioning in the following manner: a stock solution of doxorubicin was prepared in 2 wt % DMSO in 1 PBS (pH 7.4) at a concentration of 0.25 mg/mL. A 5 mg/mL concentration of crushed particles (75–150 um) of P(MAA-g-EG) or P(MAA-g-EG) containing PMMA nanoparticles to doxorubicin stock solution was allowed to stir slowly for 2 h.

Click to enlarge
Rating
Source PLoS One, 2014, 9, e94309. Doxorubicin (Adriamycin) purchased from Selleck
Method Flow Cytometry Analysis
Cell Lines K-562, DL cells
Concentrations 5.85 uM
Incubation Time 24 h
Results It was extended our observation of DOX-uptake at microscopic level for visualizing the presence of significantly higher DOX concentration intracellularly in K-562 and DL. As observed in I and J, the intracellular level of DOX is significantly higher in cells treated with DOX-PCL63-b-PNVP90 compared to free DOX suggesting high drug delivery efficiency of the compound.

Click to enlarge
Rating
Source PLoS One, 2013, 8(1), e54595. Doxorubicin (Adriamycin) purchased from Selleck
Method MTT assay
Cell Lines Huh7, THLE2, Hep5B cells
Concentrations 0.016-52 uM
Incubation Time 74 h
Results Cytotoxicity by doxorubicin was measured by MTT assay atvarying concentrations on the HCC lines Huh7, THLE2, Hep3B.

Click to enlarge
Rating
Source 2014, Dr Milica Pesic from Institute for Biological Research. Doxorubicin (Adriamycin) purchased from Selleck
Method Transwell membranes assembled
Cell Lines COR-L23, RH460 cells
Concentrations 50 nM, 1 uM
Incubation Time 24 h
Results Evaluation of DOX effect on cancer cell invasion in combination with inhibitors of CXCR4 receptor (WZ811) and focal adhesion kinase (FAK; PF-573228). Two DOX resistant non-small cell lung carcinoma (NSCLC) cell lines were employed: COR-L23 that shows intrinsic resistance to DOX and RH460 with classical acquired multidrug resistant phenotype. The results show that DOX, classical cytotoxic drug, potentates known anti-migratory effects of CXCR4 receptor inhibitor (WZ811) and FAK inhibitor (PF-573228) in both types of resistant NSCLC cell lines. WZ811 had more pronounced and significant effect with DOX in RH460 cells while PF-573228 was more effective with DOX oin COR-L23 cell line.

文献中の引用 (28)

Frequently Asked Questions

  • Question 1
    Why the IC50 of the compound varied over time in our measurement?

    Answer: Sometimes the IC50 value might vary between different batch of compounds due to the slight differences in purity. If different IC50 was seen in the same batch of compound, the problem may lies in the process of dissolvement. Make sure that you see no particles and the solution is clear with your stock solution.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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