The drug candidate LY3522348, recently highlighted by Drug Hunter, is an orally active, highly selective dual inhibitor of human ketohexokinase isoforms C and A (hKHK-C/A).

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Ketohexokinase (KHK) is an ATP-dependent enzyme, existing in two isoforms (KHK-C and KHK-A) that share high active site homology. KHK plays a crucial role in the first step of fructose metabolism - phosphorylation of the C1 OH-group, leading to fructose-1-phosphate (F1P) generation. F1P can be further utilized in the fat synthesis. Various preclinical studies have shown that KHK inhibiting has beneficial impacts on metabolic diseases, kidney and liver function. Thus, KHK inhibitors could be advantageous in the treatment of diabetes, NAFLD, NASH, CKD, and DKD.

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