Nemorubicin-Methoxymorpholinyldoxorubicin-DataSheet-生命科學試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemENemorubicinCat. No.: HY-15794CAS No.: 108852-90-0Synonyms: Methoxymorpholinyldoxorubicin; PNU 152243; PNU-152243A分式: CHNO分量: 643.64作靶點: Others作通路: Others儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)

2、體外實驗 DMSO : 47 mg/mL (73.02 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.5537 mL 7.7683 mL 15.5366 mL5 mM 0.3107 mL 1.5537 mL 3.1073 mL10 mM 0.1554 mL 0.7768 mL 1.5537 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 emorubicin種阿

3、霉素衍物，具有抗腫瘤活性。體外研究Nemorubicin has antitumor activity, with IC70s of 578 137 nM, 468 45 nM, 193 28 nM, 191 19 nM, 68 12 nM, and 131 9 nM for HT-29, A2780, DU145, EM-2, Jurkat and CEM cell lines, respectively 1.Nemorubicin acts through nucleotide excision repair (NER) system to exert its activity. Nemo

4、rubicin (0-0.3 1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEM) is more active in the L1210/DDP cells with intact NER than in the XPG-deficient L1210/0 cells. Cellsresistant to nemorubicin show increased sensitivity to UV damage 3. Nemorubicin is cytotoxic to 9L/3A4cells, with an IC50 of 0.2 nM,

5、120-fold lower than that of P450-deficient 9L cells (IC50, 23.9 nM).Nemorubicin also potently inhibits Adeno-3A4 infected U251 cells with IC50 of 1.4 nM. P450 reductaseoverexpression enhances cytotoxicity of Nemorubicin 4.體內(nèi)研究 Nemorubicin is converted to PNU-159682 by human liver cytochrome P450 (CY

6、P) 3A4 in rat, mouse, anddog liver microsomes 2. Nemorubicin (60 g/kg) induces sifnificant tumor growth delay in scid mice bearing9L/3A4 tumors, but shows no obvious effect on the tumor growth delay of 9L tumors in mice by i.v. orintratumoral injection (i.t.). Nemorubicin (40 g/kg, i.p.) exhibits no

7、 antitumor activity and no host toxicity inmice bearing 9L/3A4 tumors 4.PROTOCOLCell Assay 4 9L and CHO cells are plated in triplicate wells of a 96-well plate at 3000 cells per well 24 hr prior to drugtreatment. Cells are treated with various concentrations of Nemorubicin or IFA for 4d. Cells are t

8、hen stainedwith crystal violet (A595) and relative cell survival is calculated. IC50 values are determined from a semi-logarithmic graph of the data points using Prism 4 4.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal 9L and 9L/3A4 cells are gr

9、own as solid tumors in male ICR/Fox Chase SCID mice. Cells cultured in DMEMAdministration 4 medium to 75% confluence are trypsinized and washed in PBS and then adjusted to 2 107 cells/mL ofFBS-free DMEM. Four-week-old SCID mice (18-20 g) are implanted with either 9L or 9L/3A4 tumor cells byinjection

10、 of 4 106 cells/0.2 mL of cell suspension, s.c. on each hind flank. Tumor sizes (length and width)are measured twice a week using Vernier calipers beginning 7d after tumor implantation. When the averagetumor size reach 300 to 400 mm3, Nemorubicin dissolved in PBS is administered by tail vein injecti

11、on (i.v.) orby direct intratumoral (i.t.) injection (three injections spaced 7 d apart, each at 60 g Nemorubicin per kgbody weight). Intratumoral injections are performed using a syringe pump set a 1 L/s with a 30-gaugeneedle. Each i.t. treatment dose is divided into three injections per tumor, with

12、 the injected volume set at 50L per tumor per 25 g mouse. Thus, for a 30 g mouse, a total of 120 L of 15 g/mL of Nemorubicin solutionis administered: 20 L per site 3 sites per tumor 2 tumors/mouse. Drug-free controls are injected i.t. withthe same vol of PBS. In some experiments, Nemorubicin is admi

13、nistered by i.p. injection at 40 or 60 g/kgbody weight. Tumor sizes and body weights are measured twice/wk for the duration of the study. Tumorvolumes are calculated using the formula: V = /6 (L W)3/2. Percent tumor regression is calculated as 100 (V1-V2)/V1, where V1 is the tumor vol on the day of

14、drug treatment and V2 is the vol on the day when thelargest the decrease in tumor size is seen following drug treatment. Tumor doubling time is calculated as thetime required for tumors to double in vol after drug treatment 4.MCE has not independently confirmed the accuracy of these methods. They ar

15、e for reference only.REFERENCES1. Quintieri L, et al. Formation and antitumor activity of PNU-159682, a major metabolite of nemorubicin in human liver microsomes. ClinCancer Res. 2005 Feb 15;11(4):1608-17.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE2. Quintieri L, et al. In vitro hepatic conver

16、sion of the anticancer agent nemorubicin to its active metabolite PNU-159682 in mice, rats anddogs: a comparison with human liver microsomes. Biochem Pharmacol. 2008 Sep 15;76(6):784-95.3. Sabatino MA, et al. Down-regulation of the nucleotide excision repair gene XPG as a new mechanism of drug resistance in human andmurine cancer cells. Mol Cancer. 2010 Sep 24;9:259.4. Lu H, et al. Potentiation of methoxymorpholinyl doxorubicin antitumor activity by P450 3A4 gene t