Pharmacophore-based virtual screening and <i>in silico</i> investigations of small molecule library for discovery of human hepatic ketohexokinase inhibitors for the treatment of fructose metabolic disorders.

ABSTRACT:

Introduction

Excessive fructose consumption is a significant driver of metabolic disorders, including obesity, diabetes, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis primarily by promoting insulin resistance and fat accumulation. Ketohexokinase C (KHK-C), a pivotal enzyme in fructose metabolism, catalyzes the phosphorylation of fructose to fructose-1-phosphate, initiating a cascade of downstream metabolic processes. In contrast to glucose metabolism, KHK-C lacks negative feedback regulation, allowing the continuous phosphorylation of fructose, which leads to heightened levels of glucose, glycogen, and triglycerides in the bloodstream and liver. While targeting KHK-C offers a promising therapeutic avenue, no drugs have yet been approved for clinical use. Pfize

SUBMITTER: Elsaman T 

PROVIDER: S-EPMC12009819 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature