KHK-IN-2 is a highly potent and selective inhibitor of fructokinase (KHK) with an IC50 of 0.45μM[1]. KHK catalyzes the first step in fructose metabolism, and in animal models, KHK inhibition reduces hepatic de novo lipogenesis and steatosis and corrects many metabolic abnormalities associated with insulin resistance[2]. KHK-IN-2 can be used to study fructose metabolism-related diseases such as non-alcoholic fatty liver disease (NAFLD), diabetes, and obesity[3, 4].
References:
[1] Huard K, Ahn K, Amor P, et al. Discovery of fragment-derived small molecules for in vivo inhibition of ketohexokinase (KHK)[J]. Journal of medicinal chemistry, 2017, 60(18): 7835-7849.
[2] Kazierad D J, Chidsey K, Somayaji V R, et al. Inhibition of ketohexokinase in adults with NAFLD reduces liver fat and inflammatory markers: a randomized phase 2 trial[J]. Med, 2021, 2(7): 800-813. e3.
[3] Shepherd E L, Saborano R, Northall E, et al. Ketohexokinase inhibition improves NASH by reducing fructose-induced steatosis and fibrogenesis[J]. JHEP Reports, 2021, 3(2): 100217.
[4] Park S H, Helsley R N, Fadhul T, et al. Fructose induced KHK-C can increase ER stress independent of its effect on lipogenesis to drive liver disease in diet-induced and genetic models of NAFLD[J]. Metabolism, 2023, 145: 155591.
KHK-IN-2是一种高效，选择性的果糖激酶（KHK）抑制剂，IC50为0.45μM[1]。KHK催化果糖代谢的第一步，在动物模型中，KHK抑制可减少肝脏新生脂肪生成和脂肪变性，并纠正与胰岛素抵抗相关的许多代谢异常[2]。KHK-IN-2能够用于研究果糖代谢相关疾病，如非酒精性脂肪肝病（NAFLD）、糖尿病和肥胖症[3, 4]。