米托蒽醌二鹽酸鹽作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetMitoxantrone dihydrochlorideCat. No.: HY-13502ACAS No.: 70476-82-3分式: CHClNO分量: 517.4作靶點(diǎn): Topoisomerase; PKC作通路: Cell Cycle/DNA Damage; Epigenetics; TGF-beta/Smad儲(chǔ)存式: 4C, protect from light* In solvent : -80C, 6 months; -20C, 1 month (protect from light)溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 43 mg/mL (8

2、3.11 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 1.9327 mL 9.6637 mL 19.3274 mL5 mM 0.3865 mL 1.9327 mL 3.8655 mL10 mM 0.1933 mL 0.9664 mL 1.9327 mL請(qǐng)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(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 month (protect

3、from light)。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/m

4、L (4.83 mM); Clear solution此案可獲得 2.5 mg/mL (4.83 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (4.83 mM); Clear solution此案可獲得 2.5 mg/mL (4.83 mM，飽

5、和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合Page 1 of 2 www.MedChemE均勻。BIOLOGICAL ACTIVITY物活性 Mitoxantrone dihydrochloride M。拓?fù)洚悩?gòu)酶II (topoisomerase II)的抑制劑；也可抑制蛋激酶C (PKC)， IC50值為8.5 IC & Target Topoisomerase II PKC8.5 M (IC50)體外研究 Mitoxantrone inhibits PKC in

6、a competitive manner with respect to histone H1, and its Ki value is 6.3 M and in a non-competitive manner with respect to phosphatidylserine and ATP1. Treatment of B-CLL cells for 48 h withmitoxantrone (0.5 g/mL) induces a decrease in cell viability. Mitoxantrone induces DNA fragmentation and thepr

7、oteolytic cleavage of poly(ADP-ribose) polymerase (PARP), demonstrating that the cytotoxic effect of mitoxantroneis due to induction of apoptosis2. Mitoxantrone shows cytotoxicity to human breast carcinoma cell lines MDA-MB-231 and MCF-7 with IC50 values of 18 and 196 nM, respectively3.體內(nèi)研究 Mitoxant

8、rone given IP at the optimal dose (1.6 mg/kg/day; as a free base) produces a statistically significant numberof 60-day survivors (curative effect) in mice with IP implanted L1210 leukemia. In SC implanted Lewis lung carcinoma, mitoxantrone and ADM administered IV also shows effective antitumor activ

9、ities and produces a 60% and a 45% ILS,respectively.4.PROTOCOLCell Assay 3 The human breast carcinoma cell lines MDA-MB-231 and MCF-7 are seeded in standard 96-well plates. One day afterseeding, the culture medium is changed and replaced by medium containing different concentration of Mitoxantrone(1

10、0-5 to 5 M) with or without DHA (30 M) during 7 days. Viability of cells are measured as a whole by thetetrazolium salt assay3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: Mitoxantrone is tested for antitumor activity against experimenta

11、l tumors in mice and the results are comparedAdministration 4 with those of seven antitumor antibiotics. The drugs are given IP or IV, in general on days 1, 5, and 9 following tumorinoculation. Mitoxantrone is given IP at the optimal dose (1.6 mg/kg/day; as a free base)4.MCE has not independently co

12、nfirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) J Mol Med (Berl). 2019 Aug;97(8):1183-1193. Exp Cell Res. 2020 May 3:112054.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCESPage 2 of 3 www.MedChemE1. Takeuchi N, et al. Inhibitory effect of

13、mitoxantrone on activity of protein kinase C and growth of HL60 cells. J Biochem. 1992 Dec;112(6):762-7.2. Bellosillo B, et al. Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 1998Jan;100(1):142-6.3. Venza I, et al. Class II-spec

14、ific histone deacetylase inhibitors MC1568 and MC1575 suppress IL-8 expression in human melanoma cells. Pigment CellMelanoma Res. 2013 Mar;26(2):193-204.4. Fujimoto S, et al. Antitumor activity of mitoxantrone against murine experimental tumors: comparative analysis against various antitumor antibiotics.Cancer Chemother Pharmacol. 1982;8(2):157-62.McePdfHei