OTX008 is a selective inhibitor of galectin-1.

Galectin-1^[1].

Growth inhibitory concentrations (GI₅₀) of OTX008 in a large panel of human solid tumour cell lines ranges from 3 to 500 μM. A significant correlation between OTX008 GI₅₀ values and Gal1 mRNA (LGALS1) and protein expression levels in the panel of cancer cells is observed. In SQ20B and A2780-1A9 cells, OTX008 inhibits Gal1 expression and ERK1/2 and AKT-dependent survival pathways, and induces G2/M cell cycle arrest through CDK1. OTX008 enhances the anti-proliferative effects of Semaphorin-3A (Sema3A) in SQ20B cells and reverses invasion induced by exogenous Gal1^[1]. OTX008 affects endothelial cell proliferation, motility, invasiveness, and cord formation. Tumor cell proliferation is also inhibited, with differences in sensitivity among cell lines (IC₅₀ from 1 to 190 μM)^[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.

OTX008 inhibits growth of A2780-1A9 xenografts. OTX008 treatment is associated with down-regulation of Gal1 and Ki67 in treated tumours, as well as decreased microvessel density and VEGFR2 expression. Finally, combination studies show OTX008 synergy with several cytotoxic and targeted therapies, principally when OTX008 is administered first^[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.

937.18

C₅₂H₇₂N₈O₈

286936-40-1

Room temperature in continental US; may vary elsewhere.

Ethanol : ≥ 33.33 mg/mL (35.56 mM)

DMSO : 10 mg/mL (10.67 mM; Need ultrasonic)

* “≥” 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。-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% EtOH    90% Saline

  Solubility: ≥ 1.25 mg/mL (1.33 mM); Clear solution
• 2.

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

  Solubility: ≥ 1 mg/mL (1.07 mM); Clear solution

  此方案可获得 ≥ 1 mg/mL (1.07 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 10.0 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

• 3.

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

  Solubility: ≥ 1 mg/mL (1.07 mM); Clear solution

  此方案可获得 ≥ 1 mg/mL (1.07 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 10.0 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
• 4.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 1 mg/mL (1.07 mM); Clear solution

  此方案可获得 ≥ 1 mg/mL (1.07 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 10.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Astorgues-Xerri L, et al. OTX008, a selective small-molecule inhibitor of galectin-1, downregulates cancer cell proliferation, invasion and tumour angiogenesis. Eur J Cancer. 2014 Sep;50(14):2463-77.

  [2]. Zucchetti M, et al. Pharmacokinetics and antineoplastic activity of galectin-1-targeting OTX008 in combination with sunitinib. Cancer Chemother Pharmacol. 2013 Oct;72(4):879-87.

Mice^[1]
A total of 8×10⁶ A2780-1A9 ovarian cells are injected subcutaneously into the right lateral flank of female nu/nu athymic mice. Once tumours are palpable (50 mm³), mice are randomised to receive treatment intraperitoneally with either PBS (3 times/week), 5 mg/kg OTX008 (3 times/week), 6 mg/kg cisplatin (days 1, 8 and 15) or 10 mg/kg docetaxel (days 1, 8 and 15). Tumour size was measured twice weekly with calipers and tumour volume is calculated as 3.14×(width²)/length^[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.

• [1]. Astorgues-Xerri L, et al. OTX008, a selective small-molecule inhibitor of galectin-1, downregulates cancer cell proliferation, invasion and tumour angiogenesis. Eur J Cancer. 2014 Sep;50(14):2463-77.

  [2]. Zucchetti M, et al. Pharmacokinetics and antineoplastic activity of galectin-1-targeting OTX008 in combination with sunitinib. Cancer Chemother Pharmacol. 2013 Oct;72(4):879-87.