Doxorubicin-Hydroxydaunorubicin-DataSheet-生命科學試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEDoxorubicinCat. No.: HY-15142ACAS No.: 23214-92-8Synonyms: Hydroxydaunorubicin分式: CHNO分量: 543.52作靶點: Topoisomerase; ADC Cytotoxin; Autophagy; Mitophagy作通路: Cell Cycle/DNA Damage; Antibody-drug Conjugate/ADCRelated; Autophagy儲存式:

2、 Please store the product under the recommended conditions inthe COA.BIOLOGICAL ACTIVITY物活性 Doxorubicin種有細胞毒性的蒽環(huán)類抗素，于治療多種癌癥。Doxorubicin 在癌細胞中起作的可能機制 嵌 DNA 和破壞 topoisomerase-II 介導的DNA修復。IC50 & Target Topoisomerase II體外研究 Combination of Doxorubicin and Simvastatin in the highest tested concentrations

3、(2 M and 10 M, respec-tively) kills 97% of the Hela cells 2.體內(nèi)研究 Mice bearing PC3 xenografts are injected with 2, 4 or 8 mg/kg Doxorubicin and tumor volume is measuredover time. A dose of 2 mg/kg does not affect tumor growth while higher dosages delay tumor growth initially(p 3. A single intraperito

4、neal injection 10 mg/kg (Doxorubicin 1) is administered in rats, 10 dailyintraperitoneal injections of 1 mg/kg (Doxorubicin 2), or in 5 weekly intraperitoneal injections of 2 mg/kg(Doxorubicin 3). An 80% mortality rate is observed at day 28 in Doxorubicin 1, whereas Doxorubicin 2 andDoxorubicin 3 re

5、ached 80% mortality at days 107 and 98, respectively. Fractional shortening decreased by30% at week 2 in Doxorubicin DOX1, 55% at week 13 in Doxorubicin 2, and 42% at week 13 in Doxorubicin3 4.PROTOCOLCell Assay 2 160 L of Hela cells suspension (3104 cell/mL) is dispensed into three 96-well U-bottom

6、 microplates and1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEincubated for 24 h at 37C in a fully humidified atmosphere of 5% CO2. In plate 1, serial dilutions ofDoxorubicin (20 L; final concentration, 0.1-2 M) and Simvastatin (20 L; final concentration, 0.25-2 M) areadded to a final volume of 2

7、00 L and incubated for another 72 h. In plates 2 and 3 serial dilutions of eachdrug (Simvastatin or Doxorubicin, 40 L) are added. After an incubation period of 24 h, the medium isaspirated and the cells are washed in PBS. Then, serial dilutions of other drug (40 L) are added andsupplemented with cul

8、ture medium to a final volume of 200 L, and incubated for 48 h. Doxorubicin andSimvastatin are used individually as positive controls (40 L in each well), and the cells treated only withsolvent are considered as negative controls. To evaluate cell survival, 20 L of MTT solution (5 mg/mL inPBS) is ad

9、ded to each well and incubated for 3 h. Then the media is replaced with 150 L of DMSO, andcomplete solubilization of formazan crystals is achieved by repeated pipetting of the solution. Absorbance isthen determined at 540 nm by an ELISA plate reader. Each drug concentration is assayed in 4 or 8 well

10、s andrepeated 3 times. The cytotoxic/cytostatic effect of Doxorubicin is expressed as the relative viability (%control) and calculated. Percentage of cell survival in the negative control is assumed as 100. Relativeviability=(experimental absorbance-background absorbance)/ (absorbance of untreated c

11、ontrols-backgroundabsorbance)100 % 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 3Administration 34 Athymic male nude mice (3-4 weeks old) are used. PC3 cells (4106) are injected subcutaneously into theflanks of mice. Animals bearing tum

12、ors are randomly assigned to treatment groups (five or six mice pergroup) and treatment initated when xenografts reached volumes of about 100 mm3. Tumors are measuredusing digital calipers and volume calculated using the formula: Volume=Width2Length0.52, where widthrepresents the shorter dimension o

13、f the tumor. Treatments are administered as indicated using vehicle (PBScontaining 0.1% BSA), Doxorubicin (2-8 mg/kg), Apo2L/TRAIL (500 g/animal), or a combination of 4 mg/kgDoxorubicin followed by 500 g Apo2L/TRAIL. Doxorubicin is administered systemically whereasApo2L/TRAIL is given either intra-t

14、umorally or systemically. All treatments are given once. Mice aremonitored daily for signs of adverse effects (listlessness and scruffy apparance). Treatments seemed to bewell tolerated. The meanSEM is calculated for each data point. Differences between treatment groups areanalyzed by the student t-

15、test. Differences are considered significant when P 4Thirty male Sprague-Dawley rats weighing 250 to 300 g are randomly assigned to 1 of 3 experimentalgroups: Doxorubicin schedule 1 (Doxorubicin 1, n=10), Doxorubicin schedule 2 (Doxorubicin 2, n=10), orDoxorubicin schedule 3 (Doxorubicin 3, n=10). F

16、or all Doxorubicin treatment schedules, the cumulative doseof Doxorubicin is 10 mg/kg. Schedule 1 involves a single bolus intraperitoneal injection of Doxorubicin at 10mg/kg. Schedule 2 involves 10 intraperitoneal injections of Doxorubicin at 1 mg/kg for 10 consecutive days.Schedule 3 involves 5 int

17、raperitoneal injections of Doxorubicin at 2 mg/kg, once each week, for 5 wk.Immediately before the first Doxorubicin treatment and at weekly intervals after beginning Doxorubicintreatment, blood pressure and cardiac function are assessed in all surviving animals as long as there are atleast 3 rats p

18、er group.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Nat Med. 2016 May;22(5):547-56.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE J Clin Invest. 2018 Jan 2;128(1):483-499. Nat Commun. 2018 Oct 8;9(1):4139. Nucleic Acids Res. 2018 Apr

19、 20;46(7):3284-3297. Dev Cell. 2018 Sep 24;46(6):681-695.e5.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Nitiss JL, et al. Targeting DNA topoisomerase II in cancer chemotherapy.Nat Rev Cancer. 2009 May;9(5):338-50.2. Sadeghi-Aliabadi H, et al. Cytotoxic evaluation of doxorubicin in combination with simvastatin against human cancer cells. Res PharmSci. 2010 Jul;5(2):127-33.3. El-Zawahry A, et al. Doxorubicin increases the effectiveness of Apo2L/TRAIL for tumor growth inhibition of prostate cancerxenografts.BMC Cancer. 2005 Jan 7;5:2.4. Hayward R,