Mitoxantrone dihydrochloride is a topoisomerase II inhibitor; also inhibits protein kinase C (PKC) activity with an IC₅₀ of 8.5 μM.

Mitoxantrone inhibits PKC in a competitive manner with respect to histone H1, and its K_i value is 6.3 μM and in a non-competitive manner with respect to phosphatidylserine and ATP^[1]. Treatment of B-CLL cells for 48 h with mitoxantrone (0.5 μg/mL) induces a decrease in cell viability. Mitoxantrone induces DNA fragmentation and the proteolytic cleavage of poly(ADP-ribose) polymerase (PARP), demonstrating that the cytotoxic effect of mitoxantrone is due to induction of apoptosis^[2]. Mitoxantrone shows cytotoxicity to human breast carcinoma cell lines MDA-MB-231 and MCF-7 with IC₅₀ values of 18 and 196 nM, respectively^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Mitoxantrone given IP at the optimal dose (1.6 mg/kg/day; as a free base) produces a statistically significant number of 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 activities and produces a 60% and a 45% ILS, respectively.^[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

517.40

C₂₂H₃₀Cl₂N₄O₆

70476-82-3

米托蒽醌二盐酸盐

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture and light

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)

H₂O : 100 mg/mL (193.27 mM; Need ultrasonic)

DMSO : ≥ 43 mg/mL (83.11 mM)

* “≥” means soluble, but saturation unknown.

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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (4.83 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.83 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.5 mg/mL (4.83 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.83 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明

• [1]. Takeuchi N, et al. Inhibitory effect of 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. 1998 Jan;100(1):142-6.

  [3]. Venza I, et al. Class II-specific histone deacetylase inhibitors MC1568 and MC1575 suppress IL-8 expression in human melanoma cells. Pigment Cell Melanoma 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.

The human breast carcinoma cell lines MDA-MB-231 and MCF-7 are seeded in standard 96-well plates. One day after seeding, the culture medium is changed and replaced by medium containing different concentration of Mitoxantrone (10^-5 to 5 μM) with or without DHA (30 μM) during 7 days. Viability of cells are measured as a whole by the tetrazolium salt assay^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Mice: Mitoxantrone is tested for antitumor activity against experimental tumors in mice and the results are compared with those of seven antitumor antibiotics. The drugs are given IP or IV, in general on days 1, 5, and 9 following tumor inoculation. Mitoxantrone is given IP at the optimal dose (1.6 mg/kg/day; as a free base)^[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Takeuchi N, et al. Inhibitory effect of 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. 1998 Jan;100(1):142-6.

  [3]. Venza I, et al. Class II-specific histone deacetylase inhibitors MC1568 and MC1575 suppress IL-8 expression in human melanoma cells. Pigment Cell Melanoma 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.