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.
KC7F2是转录因子HIF-1（缺氧诱导因子-1）的抑制剂，其IC₅₀分别为20μM[1] ，KC7F2常被用于肿瘤发育和血管形成的研究中[2]。此外，KC7F2还具备改善溃疡性结肠炎、肺纤维化等功能[3-4]。
在体外，KC7F2（19–22μM）预处理U87MG胶质瘤细胞48小时，随后与替莫唑胺（TMZ，208.71μM）联合处理，显著抑制细胞增殖，诱导细胞凋亡，并降低HIF-1α蛋白水平，同时抑制与能量代谢相关的基因表达，从而增强对胶质瘤细胞的治疗效果[5]。KC7F2（20μM）预处理人脐静脉内皮细胞（HUVECs）4小时，随后在低氧条件下（1% O₂）培养6小时，显著抑制细胞活性和管状形成能力，同时降低HIF-1、活性氧（ROS）和血管内皮生长因子（VEGF）的表达[6]。
在体内，KC7F2（10mg/kg）联合GW9662（1mg/kg）处理C57BL/6J雄性小鼠，小鼠暴露于低氧环境4周。KC7F2显著抑制了低氧诱导的心脏功能障碍，同时降低了低氧诱导的心脏HIF-1的表达，并改善了心脏葡萄糖代谢 [7]。KC7F2（10mg/kg）通过腹腔注射给药处理HTRA1诱导的视网膜功能障碍模型小鼠，KC7F2显著抑制了HTRA1诱导的视网膜色素上皮细胞衰老，并改善了小鼠视网膜功能障碍[8]。