KC7F2

KC7F2 is an inhibitor of the transcription factor HIF-1 (hypoxia-inducible factor-1), with an IC₅₀ of 20μM^[1], KC7F2 is commonly used in research on tumor development and angiogenesis^[2]. In addition, KC7F2 has also been shown to improve conditions such as ulcerative colitis and pulmonary fibrosis^[3-4].

In vitro, pretreatment of U87MG glioma cells with KC7F2 (19–22μM) for 48 hours, followed by combined treatment with temozolomide (TMZ, 208.71μM), significantly inhibits cell proliferation, induces apoptosis, and reduces HIF-1α protein levels. KC7F2 also suppresses the expression of genes related to energy metabolism, thereby enhancing the therapeutic effect on glioma cells^[5]. Pretreatment of human umbilical vein endothelial cells (HUVECs) with KC7F2 (20μM) for 4 hours, followed by culture under hypoxic conditions (1% O₂) for 6 hours, significantly inhibits cell viability and tube formation, while reducing the expression of HIF-1, reactive oxygen species (ROS), and vascular endothelial growth factor (VEGF)^[6].

In vivo, C57BL/6J male mice were treated with KC7F2 (10mg/kg) in combination with GW9662 (1mg/kg) and exposed to hypoxia for 4 weeks. KC7F2 significantly prevented hypoxia-induced cardiac dysfunction, reduced HIF-1 expression in the heart, and improved cardiac glucose metabolism^[7]. In a mouse model of retinal dysfunction induced by HTRA1, KC7F2 (10mg/kg) administered via intraperitoneal injection significantly inhibited HTRA1-induced retinal pigment epithelial cell senescence and improved retinal dysfunction^[8].

References:
[1] Narita T, Yin S, Gelin CF, et al. Identification of a novel small molecule HIF-1alpha translation inhibitor. Clin Cancer Res. 2009 Oct 1;15(19):6128-36.
[2] Chen X, Kou Y, Lu Y, et al. Salidroside ameliorated hypoxia-induced tumorigenesis of BxPC-3 cells via downregulating hypoxia-inducible factor (HIF)-1α and LOXL2. J Cell Biochem. 2020 Jan;121(1):165-173.
[3] Li J, Dan W, Zhang C, et al. Exploration of Berberine Against Ulcerative Colitis via TLR4/NF-κB/HIF-1α Pathway by Bioinformatics and Experimental Validation. Drug Des Devel Ther. 2024 Jul 9;18:2847-2868.
[4] Xu X, Li Y, Niu Z, et al. Inhibition of HIF-1α Attenuates Silica-Induced Pulmonary Fibrosis. Int J Environ Res Public Health. 2022 Jun 1;19(11):6775.
[5] Abbaszade Z, Bagca BG, Avci CB. Molecular biological investigation of temozolomide and KC7F2 combination in U87MG glioma cell line. Gene. 2021 Apr 15;776:145445.
[6] Cheng J, Yang HL, Gu CJ, et al. Melatonin restricts the viability and angiogenesis of vascular endothelial cells by suppressing HIF-1α/ROS/VEGF. Int J Mol Med. 2019 Feb;43(2):945-955.
[7] Wang Y, Zhang R, Chen Q, et al. PPARγ Agonist Pioglitazone Prevents Hypoxia-induced Cardiac Dysfunction by Reprogramming Glucose Metabolism. Int J Biol Sci. 2024 Aug 6;20(11):4297-4313.
[8] Xu W, Liu X, Han W, et al. Inhibiting HIF-1 signaling alleviates HTRA1-induced RPE senescence in retinal degeneration. Cell Commun Signal. 2023 Jun 14;21(1):134.