Doxorubicin (Adriamycin) 化学構造
分子量: 579.98

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製品説明

  • Compare Topoisomerase Inhibitors
    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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Detroit562 M4TvdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFf6bFhKSzVyPUKzNE44OiCwTR?= Ml\EV2FPT0WU
NCI-H2405 NEG0RVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2rFOGlEPTB;MkO0MlEhdk1? NWj1XpFpW0GQR1XS
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LB2241-RCC NHXXUGFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVf6NoRqUUN3ME2yN|UvOTFibl2= MmrNV2FPT0WU
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PC-14 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MY\JR|UxRTJ|Nj6xNkBvVQ>? M1rVenNCVkeHUh?=
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LC4-1 M4\QfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MonJTWM2OD1{NECuPFkhdk1? MV3TRW5ITVJ?
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T-24 Mn7GS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWnncnNUUUN3ME2yOFUvPDhibl2= MnjVV2FPT0WU
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TE-9 MkHlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkPtTWM2OD1{NUeuOFchdk1? M2Tm[XNCVkeHUh?=
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NCI-H23 NX:yfVFXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnHzTWM2OD1{OEOuPVIhdk1? MWjTRW5ITVJ?
GOTO NYjWZlZCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmXLTWM2OD1{OEWuOVYhdk1? M1G2c3NCVkeHUh?=
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Ramos-2G6-4C10 NV\qe|lNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIf1SJhKSzVyPUK5OE42PSCwTR?= M1q1ZnNCVkeHUh?=
CAL-54 M2n0Rmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGq0NVZKSzVyPUOwNE44OyCwTR?= MVfTRW5ITVJ?
D-263MG NWrjbI9lT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUj2VHBoUUN3ME2zNFUvPTJibl2= MV7TRW5ITVJ?
SKG-IIIa NXzhT2JRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWfuTnNpUUN3ME2zNVEvOTRibl2= NWjnc|NVW0GQR1XS
HAL-01 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlOzTWM2OD1|MUOuOFQhdk1? MX7TRW5ITVJ?
LAN-6 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NULGXlU4UUN3ME2zNVUvOTFibl2= MmjsV2FPT0WU
NCI-H1304 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MULJR|UxRTN{MT6xO{BvVQ>? NYraTIlnW0GQR1XS
no-11 MlPiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2LvemlEPTB;M{KxMlY1KG6P NW\GdGJPW0GQR1XS
IST-MES1 MmSxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH3xdlhKSzVyPUOyN{4{PSCwTR?= NVPlWJBSW0GQR1XS
L-363 NV7yZ3ZiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M332PGlEPTB;M{K0MlQ{KG6P MYrTRW5ITVJ?
EM-2 NWm2S3h5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFewOXlKSzVyPUOyOU41OSCwTR?= MnPrV2FPT0WU
DV-90 M4jtSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYLIUWVnUUN3ME2zNlkvPDVibl2= NYT0XnlxW0GQR1XS
Saos-2 MkTkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3PIe2lEPTB;M{K5Mlk1KG6P M{naPXNCVkeHUh?=
UMC-11 MmjBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3HKbWlEPTB;M{OxMlI5KG6P NX7hU4J6W0GQR1XS
Raji MkfMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVTIb|g6UUN3ME2zN|QvPjRibl2= NGPDNo5USU6JRWK=
RXF393 NVPIPZp[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1jIcmlEPTB;M{O1MlQ{KG6P MXvTRW5ITVJ?
EW-11 Mlz0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mk\JTWM2OD1|NEGuOVYhdk1? MXLTRW5ITVJ?
BL-70 M{HmS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUPJR|UxRTN2Mj6wNUBvVQ>? MoTyV2FPT0WU
LB373-MEL-D Ml76S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX\JR|UxRTN2ND62OEBvVQ>? NEC4XpdUSU6JRWK=
LU-139 MlLVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3PlPWlEPTB;M{S0MlkzKG6P NX:0cWNVW0GQR1XS
U-87-MG MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVTJR|UxRTN2Nj6wOEBvVQ>? MX7TRW5ITVJ?
LU-65 MofHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M37XPWlEPTB;M{S2MlQhdk1? NU[5eYh1W0GQR1XS
U031 NIHwV|JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NE\JbG5KSzVyPUO1N{45PyCwTR?= MnvoV2FPT0WU
HN NXLIO2hiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWfE[ndZUUN3ME2zOVQvOjdibl2= NHTsT|dUSU6JRWK=
MHH-CAL-2 M1\T[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVTJR|UxRTN3OT6yNUBvVQ>? MmHtV2FPT0WU
NCI-H510A NGnxNVBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3nTOGlEPTB;M{W5MlU6KG6P NXv1SYNJW0GQR1XS
NB5 NFPicnFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnTsTWM2OD1|NUmuPFEhdk1? M33Bb3NCVkeHUh?=
KG-1 NFW4SmJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGTBXYlKSzVyPUO2NU42OiCwTR?= MUHTRW5ITVJ?
EFO-21 NFe2ZmRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mo[zTWM2OD1|NkGuPFUhdk1? NFjre2RUSU6JRWK=
UACC-257 M2i2VGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIHKTlhKSzVyPUO2Nk4xPSCwTR?= NHXqfm5USU6JRWK=
SW1417 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnTBTWM2OD1|NkOuNlMhdk1? NXrXdFdnW0GQR1XS
NCI-H1417 NY[2WlFGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF24SYhKSzVyPUO3NE4xPCCwTR?= Mo\hV2FPT0WU
DSH1 NFTLXVhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVXjUHp3UUN3ME2zO|IvPzJibl2= NUX2e5NZW0GQR1XS
CAKI-1 MkTWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVjOd|dOUUN3ME2zO|UvPDhibl2= MXTTRW5ITVJ?
SIMA MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXWybo9[UUN3ME2zPFEvQDZibl2= NUTBe2txW0GQR1XS
LS-1034 MnX1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUTJR|UxRTN6ND61NUBvVQ>? MWrTRW5ITVJ?
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... 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 3年-20℃
2年-80℃in solvent
別名 NSC 123127
溶解度 (25°C) * In vitro DMSO 100 mg/mL warming (172.41 mM)
Water 20 mg/mL (34.48 mM)
Ethanol <1 mg/mL
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

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.

技術サポート&よくある質問(FAQ)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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