Palifosfamide is a novel DNA alkylator and the active metabolite of ifosfamide, with antitumor activity.

Palifosfamide lysine (ZIO-201) is a stable form of palifosfamide. Palifosfamide lysine has broad activity in sarcoma lines in vitro. The IC₅₀ ranges from 2.25 ro 6.75 μM for most cell lines except OS222 (IC₅₀=31.5 μM)^[1].

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.

Tumor growth inhibition is seen in both OS31 and OS33 xenografts and the RMS xenograft resulting in a significant difference in event-free survival between the control and the treated groups. Differential gene expression of ALDH3A1 but not ALDH1A1 is noted in the OS31 xenograft^[1]. Stabilized palifosfamide administered to mice suppresses MX-1 tumor growth by greater than 80% with 17% complete antitumor responses. Oral bioavailability in rats is 48-73% of parenteral administration, and antitumor activity in mice is equivalent by both routes. Treatment with palifosfamide-tris combined with docetaxelor doxorubicin at optimal regimens results in complete tumor regression in 62-75% of mice^[2].

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.

221.02

C₄H₁₁Cl₂N₂O₂P

31645-39-3

帕利伐米

Room temperature in continental US; may vary elsewhere.

-20°C, protect from light, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

DMSO : 40 mg/mL (180.98 mM; Need ultrasonic)

H₂O : 14.29 mg/mL (64.65 mM; Need ultrasonic)

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 (protect from light, stored under nitrogen)。-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: ≥ 3 mg/mL (13.57 mM); Clear solution

  此方案可获得 ≥ 3 mg/mL (13.57 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 30.0 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: ≥ 3 mg/mL (13.57 mM); Clear solution

  此方案可获得 ≥ 3 mg/mL (13.57 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 30.0 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
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 3 mg/mL (13.57 mM); Clear solution

  此方案可获得 ≥ 3 mg/mL (13.57 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 30.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Hingorani P, et al. Preclinical activity of palifosfamide lysine (ZIO-201) in pediatric sarcomas including oxazaphosphorine-resistant osteosarcoma. Cancer Chemother Pharmacol. 2009 Sep;64(4):733-40.

  [2]. Jones B, et al. Anticancer activity of stabilized palifosfamide in vivo: schedule effects, oral bioavailability, and enhanced activity with docetaxel and doxorubicin. Anticancer Drugs. 2012 Feb;23(2):173-84.

Palifosfamide is dissolved in phosphate buffered saline (PBS). Cells are plated in 96-well microtiter plates with approximately 500 cells per well in 100 μL of media. After 24 h of incubation at 37°C, cells are treated with increasing concentrations of palifosfamide lysine in separate plates either as a single-day treatment or three consecutive days of treatment, with fresh drug being added each day. The plates are incubated for 72 h at 37°C with 5% CO₂. After 72 h, 250 μg of MTT is added to each well and incubated at 37°C for 6 h. MTT is converted to formazine crystals by mitochondria of viable cells, which are then dissolved in 100 μL of dimethyl sulfoxide. Optical density is measured at 595 nm^[2].

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: CB17 female SCID mice are used in the study. Once the tumors reached 50–150 mm³, mice are randomized into control and treatment groups (5-8 mice/group) for each tumor line. Cyclophosphamide is administered at the dose of 150 mg/kg intraperitoneally once a week for 6 weeks. Palifosfamide lysine is administered intravenously at the maximum tolerated dose of 100 mg/kg for three consecutive days as a one-time treatment and serial tumor volumes are determined over the next 6 weeks. Mice are sacrificed at the end of the experiment^[2].

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]. Hingorani P, et al. Preclinical activity of palifosfamide lysine (ZIO-201) in pediatric sarcomas including oxazaphosphorine-resistant osteosarcoma. Cancer Chemother Pharmacol. 2009 Sep;64(4):733-40.

  [2]. Jones B, et al. Anticancer activity of stabilized palifosfamide in vivo: schedule effects, oral bioavailability, and enhanced activity with docetaxel and doxorubicin. Anticancer Drugs. 2012 Feb;23(2):173-84.