Doxorubicin-hydrochloride-Hydroxydaunorubicin-hydrochloride-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEDoxorubicin hydrochlorideCat. No.: HY-15142CAS No.: 25316-40-9Synonyms: Hydroxydaunorubicin (hydrochloride)分式: CHClNO分量: 579.98作靶点: Topoisomerase; ADC Cytotoxin; Autophagy; Mitophagy;AMPK作通路: Cell Cycle/DNA Damage; Antibody-drug

2、 Conjugate/ADCRelated; Autophagy; Epigenetics; PI3K/Akt/mTOR储存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect fromlight)溶解性数据体外实验 DMSO : 50 mg/mL (86.21 mM; Need ultrasonic)H2O : 50 mg/mL (86.21 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Con

3、centration制备储备液1 mM 1.7242 mL 8.6210 mL 17.2420 mL5 mM 0.3448 mL 1.7242 mL 3.4484 mL10 mM 0.1724 mL 0.8621 mL 1.7242 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种

4、溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.31 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (4.31 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Doxorubicin hydrochloride种有细胞毒性的蒽环类抗素，于

5、治疗多种癌症。Doxorubicin 在癌细胞中起作的可能机制 嵌 DNA 和破坏 topoisomerase-II 介导的DNA修复。IC50 & Target Topoisomerase II体外研究 Combination of Doxorubicin and Simvastatin in the highest tested concentrations (2 M and 10 M,respectively) kills 97% of the Hela cells 2.体内研究 Mice bearing PC3 xenografts are injected with 2, 4 or

6、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 intraperitoneal injection 10 mg/kg (Doxorubicin 1) is administered in rats, 10 dailyintraperitoneal injections of 1 mg/kg (Doxorub

7、icin 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 reached 80% mortality at days 107 and 98, respectively. Fractional shortening decreased by30% at week 2 in Doxorubicin DO

8、X1, 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 microplates andincubated for 24 h at 37C in a fully humidified atmosphere of 5% CO2. In plate 1, serial dilutions ofDo

9、xorubicin (20 L; final concentration, 0.1-2 M) and Simvastatin (20 L; final concentration, 0.25-2 M) areadded to a final volume of 200 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, th

10、e medium isaspirated and the cells are washed in PBS. Then, serial dilutions of other drug (40 L) are added andsupplemented with culture 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

11、 treated only withsolvent are considered as negative controls. To evaluate cell survival, 20 L of MTT solution (5 mg/mL inPBS) is added 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

12、 of the solution. Absorbance isthen determined at 540 nm by an ELISA plate reader. Each drug concentration is assayed in 4 or 8 wells andrepeated 3 times. The cytotoxic/cytostatic effect of Doxorubicin is expressed as the relative viability (%control) and calculated. Percentage of cell survival in t

13、he negative control is assumed as 100. Relativeviability=(experimental absorbance-background absorbance)/ (absorbance of untreated controls-backgroundabsorbance)100 % 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 32/3 Master of Small Mol

14、ecules 您边的抑制剂师www.MedChemEAdministration 34 Athymic male nude mice (3-4 weeks old) are used. PC3 cells (4106) are injected subcutaneously into theflanks of mice. Animals bearing tumors are randomly assigned to treatment groups (five or six mice pergroup) and treatment initated when xenografts reache

15、d volumes of about 100 mm3. Tumors are measuredusing digital calipers and volume calculated using the formula: Volume=Width2Length0.52, where widthrepresents the shorter dimension of the tumor. Treatments are administered as indicated using vehicle (PBScontaining 0.1% BSA), Doxorubicin (2-8 mg/kg),

16、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-tumorally or systemically. All treatments are given once. Mice aremonitored daily for signs of adverse effects (listless

17、ness 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-test. Differences are considered significant when P 4Thirty male Sprague-Dawley rats weighing 250 to 300 g are randomly

18、 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). For all Doxorubicin treatment schedules, the cumulative doseof Doxorubicin is 10 mg/kg. Schedule 1 involves a single bol

19、us 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 intraperitoneal injections of Doxorubicin at 2 mg/kg, once each week, for 5 wk.Immediately before the first Doxorubicin tr

20、eatment 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 per group.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Nat

21、 Med. 2016 May;22(5):547-56. J Clin Invest. 2018 Jan 2;128(1):483-499. Nat Commun. 2018 Oct 8;9(1):4139. Nucleic Acids Res. 2018 Apr 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