HO-1-IN-1 hydrochloride is a heme oxygenase 1 (HO-1) inhibitor with an IC50 of 0.25μM[1]. HO-1 is an inducible enzyme that plays a key role in maintaining cellular redox balance and protecting cells from oxidative stress by catalyzing the degradation of heme to produce carbon monoxide, biliverdin, and free iron[2][3]. HO-1-IN-1 hydrochloride is usually used in studies related to oxidative stress, inflammatory responses, and apoptosis[4][5].
In vitro, HO-1-IN-1 hydrochloride (10μM; 4h) attenuated GRIM-19 deficiency-induced NF-κB activation and p65 nuclear translocation in GES-1 cells[6]. HO-1-IN-1 hydrochloride (5-10μM; 6h) significantly attenuated GRIM-19 deficiency-driven gastric cancer cell migration and invasion, and downregulated metastasis-associated gene expressions such as HIF-1α, COX-2, VEGF-A, VEGF-C, MMP-9, and BACH-1[7].
References:
[1] Floresta G, Pittalà V, Sorrenti V, Romeo G, Salerno L, Rescifina A. Development of new HO-1 inhibitors by a thorough scaffold-hopping analysis. Bioorg Chem. 2018;81:334-339.
[2] Consoli V, Sorrenti V, Grosso S, Vanella L. Heme Oxygenase-1 Signaling and Redox Homeostasis in Physiopathological Conditions. Biomolecules. 2021;11(4):589.
[3] Ryter SW. Heme oxygenase-1/carbon monoxide as modulators of autophagy and inflammation. Arch Biochem Biophys. 2019;678:108186.
[4] Lu JJ, Abudukeyoumu A, Zhang X, Liu LB, Li MQ, Xie F. Heme oxygenase 1: a novel oncogene in multiple gynecological cancers. Int J Biol Sci. 2021;17(9):2252-2261.
[5] Spampinato M, Sferrazzo G, Pittalà V, et al. Non-competitive heme oxygenase-1 activity inhibitor reduces non-small cell lung cancer glutathione content and regulates cell proliferation. Mol Biol Rep. 2020;47(3):1949-1964.
[6] Zeng X, Yang M, Ye T, et al. Mitochondrial GRIM-19 loss in parietal cells promotes spasmolytic polypeptide-expressing metaplasia through NLR family pyrin domain-containing 3 (NLRP3)-mediated IL-33 activation via a reactive oxygen species (ROS) -NRF2- Heme oxygenase-1(HO-1)-NF-кB axis. Free Radic Biol Med. 2023;202:46-61.
[7] Wang X, Ye T, Xue B, et al. Mitochondrial GRIM-19 deficiency facilitates gastric cancer metastasis through oncogenic ROS-NRF2-HO-1 axis via a NRF2-HO-1 loop. Gastric Cancer. 2021;24(1):117-132.
HO-1-IN-1 hydrochloride是一种血红素氧合酶-1（HO-1）抑制剂，其IC50为 0.25μM[1。HO-1是一种可诱导酶，通过催化血红素降解产生一氧化碳、胆绿素和游离铁，从而在维持细胞氧化还原平衡和保护细胞免受氧化应激方面发挥关键作用[2][3]。HO-1-IN-1 hydrochloride 通常用于氧化应激、炎症反应和凋亡相关研究[4][5]。
在体外实验中，HO-1-IN-1 hydrochloride（10μM；4小时）可减轻GRIM-19缺陷诱导的GES-1细胞中NF-κB激活和p65核转位[6]。此外，HO-1-IN-1 hydrochloride（5-10μM；6小时）显著抑制GRIM-19缺陷驱动的胃癌细胞迁移和侵袭，并下调HIF-1α、COX-2、VEGF-A、VEGF-C、MMP-9和BACH-1等与肿瘤转移相关的基因表达[7]。