Tetrac (Tetraiodothyroacetic acid), a derivative of L-thyroxine (T4), is a thyrointegrin receptor antagonist. Tetrac blocks the actions of T4 and 3,5,3'-triiodo-L-thyronine (T3) at the cell surface receptor for thyroid hormone on integrin αvβ3. Tetra has anti-angiogenic and anti-tumor activities[1][2].
Tetrac (0.01-1 μM; 2-6 d) induces anti-proliferation in HT-29 and HCT116 cells with different K-RAS status[3].Tetrac (0.1 μM; 30 min) inhibits activation of ERK1/2 in HT-29 and HCT116 cells[3].Tetrac (0.1 μM; 24 h) inhibits expression of CCND1 and c-Myc, but promotes expression of CASP2 and THBS1[3]. Cell Proliferation Assay[3] Cell Line: HT-29 and HCT116 cells
Tetrac (35 μg; p.o. for 40 days) inhibits tumor inoculation, growth and integrin expression in mice[4]. Animal Model: Wild-type male Balb/C mice aged 8 weeks are inoculated with 102B16F10 or B16LS9 cells[4]
[1]. Schmohl KA, et, al. Tetrac as an anti-angiogenic agent in cancer. Endocr Relat Cancer. 2019 Jun 1; 26(6):R287-R304. [2]. Davis PJ, et, al. Nongenomic Actions of Thyroid Hormone: the Integrin Component. Physiol Rev. 2020 Jun 25. [3]. Chin YT, et, al. Tetrac and NDAT Induce Anti-proliferation via Integrin αvβ3 in Colorectal Cancers With Different K-RAS Status. Front Endocrinol (Lausanne). 2019 Mar 12; 10:130. [4]. Ashur-Fabian O, et, al. Tetrac Delayed the Onset of Ocular Melanoma in an Orthotopic Mouse Model. Front Endocrinol (Lausanne). 2019 Jan 8; 9:775. [5]. Rajabi M, et, al. Synthesis of new analogs of tetraiodothyroacetic acid (tetrac) as novel angiogenesis inhibitors for treatment of cancer. Bioorg Med Chem Lett. 2018 Apr 15;28(7):1223-1227.