KHK-IN-1 (ketohexokinase inhibitor) is a selective and cell membrane-permeable ketohexokinase (KHK) inhibitor with an IC50 value of 12nM [1]. KHK-IN-1 hydrochloride inhibits the activity of KHK by docking within the ATP-binding pocket of KHK, with a good solubility[2]. KHK-IN-1 hydrochloride has been widely used to inhibit the C. auris strain 0390 and prevent the formation of biofilms[3].
In vitro, KHK-IN-1 hydrochloride treatment for 4 days significantly inhibited the proliferation of NCI-N87 and HGC-27 cells, with IC50 values of 3.66μM and 2.31μM, respectively[4].
In vivo, KHK-IN-1 hydrochloride treatment via daily peritumoral injection of 100μl (50μM) for 14 days significantly inhibited tumor growth in the NCI-N87-xenograft mouse models, without affecting the body weight of the mice[4].
References:
[1] Maryanoff B E, O’Neill J C, McComsey D F, et al. Pyrimidinopyrimidine inhibitors of ketohexokinase: exploring the ring C2 group that interacts with Asp-27B in the ligand binding pocket[J]. Bioorganic & medicinal chemistry letters, 2012, 22(16): 5326-5329.
[2] Maryanoff B E, O'Neill J C, McComsey D F, et al. Inhibitors of ketohexokinase: discovery of pyrimidinopyrimidines with specific substitution that complements the ATP-binding site[J]. ACS medicinal chemistry letters, 2011, 2(7): 538-543.
[3] Ajetunmobi O H, Wall G, Vidal Bonifacio B, et al. High-throughput screening of the repurposing hub library to identify drugs with novel inhibitory activity against Candida albicans and Candida auris biofilms[J]. Journal of Fungi, 2023, 9(9): 879.
[4] Ma G, Liu S, Cai F, et al. Ketohexokinase-A deficiency attenuates the proliferation via reducing β-catenin in gastric cancer cells[J]. Experimental Cell Research, 2024, 438(1): 114038.
KHK-IN-1 (ketohexokinase inhibitor)是一种选择性、细胞膜渗透性的己酮糖激酶（KHK）抑制剂，IC50值为12nM[1]。KHK-IN-1 hydrochloride通过对接至KHK的ATP结合口袋内来抑制KHK活性，且具有良好溶解性[2]。KHK-IN-1 hydrochloride已被广泛用于抑制C. auris strain 0390并防止生物膜形成[3]。
在体外，KHK-IN-1 hydrochloride处理4天显著抑制了NCI-N87和HGC-27细胞的增殖，IC50值分别为 3.66μM和2.31μM[4]。
在体内，每日瘤周注射100µl（50μM）KHK-IN-1 hydrochloride，连续14天，显著抑制了NCI-N87异种移植小鼠模型中的肿瘤生长，且未影响小鼠体重[4]。