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]。