OTX008はガレクチン-1の選択的な阻害剤である[1]。OTX008は、Gal-1のβプリーツ折り畳みドメインと特異的に結合し、酸化とプロテアソームの分解を誘発し、よって腫瘍細胞の増殖、侵入と血管新生を阻害する[2]。OTX008は、数多くの固形腫瘍の治療に使われる[3-4]。
ARPE-19細胞で、OTX008 (2.5-10µM；4時間)の処理は、高いグルコースで、細胞の生存率を著しく増やした[5]。OSSC細胞で、OTX008 (12.5-100μg/mL；24-72時間)は細胞の生存率を用量依存的に減らす[6]。
SQ20B細胞異種移植マウスモデルで、OTX008 (10mg/kg；腹腔内注射；21日間)は腫瘍の成長を阻害する[7]。293FT細胞異種移植マウスモデルで、OTX008 (3mg/kg；腹腔内注射；3日間)は腫瘍の成長を阻害する[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.