IDF-11774 is an orally administered HIF-1α inhibitor, with an IC50 value of 3.65μM[1]. IDF-11774 inhibits the function of HSP70 chaperone proteins by binding to the allosteric pocket of HSP70, thereby preventing the refolding of HIF-1α and promoting HIF-1α degradation[2]. IDF-11774 decreases the oxygen consumption rate (OCR) and ATP production, thereby increasing intracellular oxygen tension[3]. IDF-11774 has been widely used in preclinical models to restrain the invasion and proliferation of various cancer cells[4].
In vitro, IDF-11774 treatment for 48 hours significantly reduced the viability of orbital fibroblasts, with IC50 values of 58.62µM and 51.51µM under normoxic and hypoxic conditions, respectively[5]. Incubation of IDF-11774 for 24 hours markedly suppressed MDA-MB-231 cells and HepG2 cells, with IC50 values of 44.19µM and 13.15µM, respectively[6]. Treatment with 30µM IDF-11774 for 4 hours induced cell cycle arrest and apoptosis in MKN45 cells and activated the MAPK signaling pathway[7].
In vivo, IDF-11774 treatment via oral administration at a dose of 60mg/kg/day for 14 days reduced the volume and local invasiveness of B16F10 melanoma in nude mice[8]. In an oxygen-induced retinopathy mouse model, intravitreal injection of IDF-11774 at a dose of 18.4ng reduced retinal neovascularization, facilitated revascularization in the vascular obliterated zone, and alleviated vascular leakage within 5 days[9].
References:[1] Ban H S, Kim B K, Lee H, et al. The novel hypoxia-inducible factor-1α inhibitor IDF-11774 regulates cancer metabolism, thereby suppressing tumor growth[J]. Cell death & disease, 2017, 8(6): e2843-e2843.
[2] Ban H S, Naik R, Kim H M, et al. Identification of targets of the HIF-1 inhibitor IDF-11774 using alkyne-conjugated photoaffinity probes[J]. Bioconjugate Chemistry, 2016, 27(8): 1911-1920.
[3] Lee K, Ban H S, Naik R, et al. Identification of malate dehydrogenase 2 as a target protein of the HIF‐1 inhibitor LW6 using chemical probes[J]. Angewandte Chemie International Edition, 2013, 52(39): 10286-10289.
[4] Kim M H, Lee T H, Lee J S, et al. Hif-1α inhibitors could successfully inhibit the progression of differentiated thyroid cancer in vitro[J]. Pharmaceuticals, 2020, 13(9): 208.
[5] Lee J, Lee J, Baek H, et al. In vitro investigation of HIF-1α as a therapeutic target for thyroid-associated ophthalmopathy[J]. Endocrinology and Metabolism, 2024, 39(5): 767-776.
[6] Li Y, Zhu R, He X, et al. Discovery of potent hypoxia-inducible factor-1α (HIF-1α) degraders by proteolysis targeting chimera (PROTAC)[J]. Bioorganic Chemistry, 2024, 153: 107943.
[7] Kim W H, Kim M J, Jin J O, et al. IDF-11774 induces cell cycle arrest and apoptosis by inhibiting HIF-1α in gastric cancer[J]. Pharmaceutics, 2023, 15(12): 2772.
[8] Kim N H, Jeong J H, Park Y J, et al. Anti-tumor Effect of IDF-11774, an inhibitor of Hypoxia-Inducible Factor-1, on Melanoma[J]. Biomolecules & Therapeutics, 2022, 30(5): 465.
[9] Yang F, Lin J, Yang B, et al. Inhibition of Endothelial HIF-1α by IDF-11774 Attenuates Retinal Neovascularization and Vascular Leakage[J]. Investigative Ophthalmology & Visual Science, 2025, 66(9): 47-47.