Doxorubicin (Adriamycin) 化学構造
分子量: 579.98

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製品説明

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  • 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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ME180 MY\DfZRwfG:6aXOgRZN{[Xl? NWLyU3RHPDhiaB?= NF;LNpVKSzVyPUCuN|kh|ryP M{f2XFI1PDh5MUi4
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KU-19-19 NFKxPYdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUTJR|UxRTJwMk[5NVch|ryP NEf4[lBUSU6JRWK=
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EVSA-T MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXfaR3dVUUN3ME2yMlMxODh7IN88US=> Mnr4V2FPT0WU
HCT-15 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn7TTWM2OD1{LkO1OFY3KM7:TR?= NET0UItUSU6JRWK=
HuO-3N1 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mo\3TWM2OD1{LkO2OVg{KM7:TR?= NW\YfI5iW0GQR1XS
GMS-10 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV\JR|UxRTJwM{m3N|gh|ryP MkHiV2FPT0WU
TGBC24TKB NF\0SlZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVTxPYczUUN3ME2yMlQyPDJ7IN88US=> MlroV2FPT0WU
C2BBe1 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlnkTWM2OD1{LkWxN|I5KM7:TR?= NFnP[5BUSU6JRWK=
SK-N-DZ NFnCcopIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2fwUmlEPTB;Mj61OlU6OiEQvF2= NWCye2tSW0GQR1XS
SK-N-AS NIjSVVhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M37vdmlEPTB;Mj63N|AyPSEQvF2= NFj2fHFUSU6JRWK=
T98G M1zVNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGHXXo1KSzVyPUKuPFA1ODFizszN MmjuV2FPT0WU
DMS-79 M4\oNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUPwOoM4UUN3ME2yMlkxQTh6IN88US=> M2S2WnNCVkeHUh?=
SNU-475 M{DnZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFX1VlhKSzVyPUKuPVI2PzJizszN NVnVNmQ5W0GQR1XS
COLO-792 NVfvV4ZVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYHJR|UxRTNwMEK4O{DPxE1? Ml;KV2FPT0WU
YAPC MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFy2NnZKSzVyPUOuN|I5OzJizszN MkLzV2FPT0WU
UACC-812 NULhUXdyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF3sbZJKSzVyPUOuN|M4OzhizszN NWjlfYdMW0GQR1XS
Mewo M122fmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWDwfVZ1UUN3ME2zMlQ3ODh4IN88US=> M3XRZXNCVkeHUh?=
COLO-824 MnHFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX7JR|UxRTNwNUezO|gh|ryP MV\TRW5ITVJ?
SCC-9 M3Trd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX\JR|UxRTNwOUGzNFkh|ryP NXLIOYNMW0GQR1XS
CP50-MEL-B NYTBVFMxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWrJR|UxRTNwOUi3NFMh|ryP NIn2c|BUSU6JRWK=
NCI-H345 NHroWYdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlviTWM2OD12LkCxNVc1KM7:TR?= MmHwV2FPT0WU
COR-L88 M2TNZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFjQRVVKSzVyPUSuN|k2QCEQvF2= M1vmWXNCVkeHUh?=
RCM-1 NIHTeJBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVfyZYVDUUN3ME20MlQ6Ojd{IN88US=> NVWxTWFkW0GQR1XS
JVM-3 NGH5bHhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4S2[GlEPTB;ND62NFYyQCEQvF2= M2jVeHNCVkeHUh?=
ECC4 MnrDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVqwcHhSUUN3ME20Mlc3PTRzIN88US=> NYPrTHgxW0GQR1XS
MDA-MB-453 NFTteIJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlP3TWM2OD12Lki1NVM1KM7:TR?= M1[xVHNCVkeHUh?=
SK-N-FI MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYHJR|UxRTVwMkK4O|ch|ryP MWXTRW5ITVJ?
D-502MG MorRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHPpZZNKSzVyPUWuNlQzPjJizszN MVvTRW5ITVJ?
NCI-H2227 MlT2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVHJR|UxRTVwM{[yN|Eh|ryP NEPyc4FUSU6JRWK=
DMS-53 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1jEUGlEPTB;Nj6xO|ExPiEQvF2= NUKwTJJpW0GQR1XS
LB771-HNC MmHDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlTqTWM2OD14LkS2PFA3KM7:TR?= NV3jb29[W0GQR1XS
BB49-HNC NHu4TG1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVLLSlJyUUN3ME23MlQyPzlzIN88US=> MXrTRW5ITVJ?
MDA-MB-415 M4m0V2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUjVU2JHUUN3ME23MlU4OzB|IN88US=> Mn\mV2FPT0WU
TALL-1 NVvyZWl6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoLHTWM2OD15Lkm2PFgh|ryP M3rTUHNCVkeHUh?=
HCC1395 M{O3U2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXK0SFZ4UUN3ME24MlE2OTJ{IN88US=> MkXGV2FPT0WU
EFE-184 NYXVV41CT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGXoPItKSzVyPUiuN|czOTZizszN NVm1[m5{W0GQR1XS
EC-GI-10 NGnDTnpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUjJR|UxRThwNki2PFYh|ryP MkjvV2FPT0WU
TT NHiwNI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mm\3TWM2OD17LkC2PVY3KM7:TR?= MkjnV2FPT0WU
U-2-OS MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXnqfpA6UUN3ME25MlgyOzl|IN88US=> NGHrOm1USU6JRWK=
SHP-77 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1f3bmlEPTB;OT65NFI6KM7:TR?= NFXUPINUSU6JRWK=
HCC1143 M2HUWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVroS2I4UUN3ME2xNE41Pzl5IN88US=> NXrLfphDW0GQR1XS
A498 M1PBV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGm3[oRKSzVyPUG4MlI6PzZizszN M1u0WnNCVkeHUh?=
LS-513 NYLDbHlGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIXo[3hKSzVyPUG4MlYxQTNizszN MVvTRW5ITVJ?
K052 M37rVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGPmcVhKSzVyPUKxMlQ1OThizszN NUf2XnI{W0GQR1XS
SiHa MkXyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3XpRWlEPTB;MkOuN|M4OSEQvF2= NV3icXNVW0GQR1XS
RCC10RGB NH;I[W9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M13tdGlEPTB;M{CuNFYyOSEQvF2= NYPkfnZ2W0GQR1XS
NCI-SNU-16 NIXPVnhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX3oe4NKUUN3ME2zNU4yQDN4IN88US=> MmD3V2FPT0WU
SNU-C1 M{DiWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoS5TWM2OD1|Mj60NVc2KM7:TR?= MkXqV2FPT0WU
C32 M1m3Nmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXrkTld{UUN3ME2zNk45PzJizszN MmPxV2FPT0WU
SW684 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4W3XWlEPTB;M{SuNVU3OSEQvF2= NXzCeG14W0GQR1XS
SK-MEL-28 M3fTNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFvkbGxKSzVyPUO1MlU{PzdizszN MlLDV2FPT0WU
SK-MEL-1 M37wSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYjJR|UxRTN4Lke1OFch|ryP M3fGb3NCVkeHUh?=
NCI-H720 NG\ldZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFnwSmVKSzVyPUSxMlk4OjZizszN MVLTRW5ITVJ?
P31-FUJ Mn3qS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4LycWlEPTB;NESuN|I5PCEQvF2= M{\vfnNCVkeHUh?=
NCI-H524 M37tUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2\6XmlEPTB;NEiuPFI1QCEQvF2= Mn;sV2FPT0WU

... 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 warmed (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)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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