OTX008
(Synonyms: Calixarene 0118; PTX008) 目录号 : GC18756
OTX008是半乳糖凝集素-1（Galectin-1）的选择性抑制剂。
Cas No.:286936-40-1
Sample solution is provided at 25 µL, 10mM.
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OTX008 is a selective inhibitor of galectin-1 [1]. OTX008 specifically binds to the β-pleated folded domain of Gal-1, inducing oxidation and proteasomal degradation, thereby inhibiting tumor cell proliferation, invasion, and angiogenesis [2]. OTX008 is indicated for the treatment of various solid tumors [3-4].
In ARPE-19 cells, OTX008 (2.5-10µM; 4h) treatment significantly increased cell viability in high glucose [5]. In OSSC cells, OTX008 (12.5-100μg/mL; 24-72h) reduces cell viability in a dose-dependent manner [6].
In SQ20B cells xenograft mice model, OTX008 (10mg/kg; ip; 21d) inhibits tumor growth [7]. In 293FT cells xenograft mice model, OTX008 (3mg/kg; ip; 3d) inhibits tumor growth [8].
References:
[1]. Astorgues-Xerri L, Riveiro M E, Tijeras-Raballand A, et al. OTX008, a selective small-molecule inhibitor of galectin-1, downregulates cancer cell proliferation, invasion and tumour angiogenesis[J]. European journal of cancer, 2014, 50(14): 2463-2477.
[2]. Delord J P, Awada A, Raymond E, et al. Abstract A72: A first-in-man Phase I study of the galectin-1 (gal-1) inhibitor OTX008 given subcutaneously as a single agent to patients with advanced solid tumors[J]. Molecular Cancer Therapeutics, 2013, 12(11_Supplement): A72-A72.
[3]. Zucchetti M, Bonezzi K, Frapolli R, et al. Pharmacokinetics and antineoplastic activity of galectin-1-targeting OTX008 in combination with sunitinib[J]. Cancer chemotherapy and pharmacology, 2013, 72(4): 879-887.
[4]. Rezai K, Durand S, Lachaux N, et al. OTX008 pharmacokinetics (PK) during the first-in-man phase I study in patients with advanced solid tumors[J]. Cancer Research, 2013, 73(8_Supplement): 33-33.
[5]. Trotta M C, Petrillo F, Gesualdo C, et al. Effects of the Calix [4] arene derivative compound OTX008 on high glucose-stimulated ARPE-19 cells: Focus on galectin-1/TGF-β/EMT pathway[J]. Molecules, 2022, 27(15): 4785.
[6]. Greer P. Effects of OTX008, a galectin-1 inhibitor, on oral squamous cell carcinoma cells in vitro[D]. University of Otago, 2018.
[7]. Koonce N A, Griffin R J, Dings R P M. Galectin-1 inhibitor OTX008 induces tumor vessel normalization and tumor growth inhibition in human head and neck squamous cell carcinoma models[J]. International journal of molecular sciences, 2017, 18(12): 2671.
[8]. Leung Z, Ko F C F, Tey S K, et al. Galectin-1 promotes hepatocellular carcinoma and the combined therapeutic effect of OTX008 galectin-1 inhibitor and sorafenib in tumor cells[J]. Journal of Experimental & Clinical Cancer Research, 2019, 38(1): 423.
OTX008是半乳糖凝集素-1（Galectin-1）的选择性抑制剂 [1]。OTX008特异性结合半乳糖凝集素-1（Galectin-1）的β折叠结构域，诱导氧化和蛋白酶体降解，从而抑制肿瘤细胞增殖、侵袭和血管生成 [2]。OTX008适用于治疗多种实体瘤 [3-4]。
在ARPE-19细胞中，OTX008（2.5-10µM；4h）处理显著提高了高糖环境下的细胞活力 [5]。在OSSC细胞中，OTX008（12.5-100μg/mL；24-72h）以剂量依赖性方式降低细胞活力 [6]。
在SQ20B细胞异种移植小鼠模型中，OTX008（10mg/kg；ip；21d）抑制了肿瘤生长 [7]。在293FT细胞异种移植小鼠模型中，OTX008（3mg/kg；ip；3d）抑制肿瘤生长 [8]。
| Cell experiment [1]: | |
Cell lines | ARPE-19 cells |
Preparation Method | Human ARPE-19 cells were cultured in Dulbecco's Modified Eagle Medium/Nutrient Mixture F12 (DMEM/F12) at 37℃ and 5% CO2 with 5mM glucose. The culture medium was supplemented with 10% heat-inactivated fetal bovine serum (FBS), 1% penicillin/streptomycin solution (P/S), 1% L-glutamine (L-Glu), 5mM Hepes, and 7.5% NaHCO3. Two days after plating, cells were split and seeded into separate culture dishes at varying cell densities for each experiment. For the first three days, cells were exposed to 5mM D-glucose (normal glucose, NG); 35mM D-glucose (high glucose, HG); and 5mM D-glucose and 30mM mannitol (NG+M) (as a negative control for high glucose) at 37℃ and 5% CO2. Then, after 72h of NG or HG stimulation, OTX008 was dissolved in 0.1% w/v dimethyl sulfoxide (DMSO) as a vehicle or 0.1% DMSO in fresh cell culture medium (NG or HG) and added daily until day 9. |
Reaction Conditions | 2.5-10µM; 4h |
Applications | OTX008 treatment significantly increased cell viability in high glucose. |
| Animal experiment [2]: | |
Animal models | SQ20B cells xenograft mice model |
Preparation Method | For the xenograft model, female athymic nude mice (Nu/Nu, 5-6 weeks old) were inoculated subcutaneously with tumor cells into the right abdominal cavity. When tumors reached approximately 100 cubic millimeters, animals were randomly assigned to treatment groups and began receiving OTX008. A total of 92 animals were inoculated, and 76 tumor-bearing animals were randomized before the start of intervention. |
Dosage form | 10mg/kg; ip; 21d |
Applications | OTX008 inhibits tumor growth. |
References: | |
| Cas No. | 286936-40-1 | SDF | |
| 别名 | Calixarene 0118; PTX008 | ||
| 化学名 | 2,2',2'',2'''-[pentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(25),3,5,7(28),9,11,13(27),15,17,19(26),21,23-dodecaene-25,26,27,28-tetrayltetrakis(oxy)]tetrakis[N-[2-(dimethylamino)ethyl]-acetamide | ||
| Canonical SMILES | O=C(NCCN(C)C)COC1=C(C2)C=CC=C1CC3=CC=CC(CC4=CC=CC(CC5=CC=CC2=C5OCC(NCCN(C)C)=O)=C4OCC(NCCN(C)C)=O)=C3OCC(NCCN(C)C)=O | ||
| 分子式 | C52H72N8O8 | 分子量 | 937.2 |
| 溶解度 | DMF: 1 mg/ml,DMSO: 2 mg/ml,Ethanol: 5 mg/ml,PBS (pH 7.2): 0.5 mg/ml | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.067 mL | 5.335 mL | 10.6701 mL |
| 5 mM | 213.4 μL | 1.067 mL | 2.134 mL |
| 10 mM | 106.7 μL | 533.5 μL | 1.067 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
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