What drugs are structurally similar to daprodustat?

Daprodustat belongs to the HIF-PHI (hypoxia-inducible factor prolyl hydroxylase inhibitor) class of oral drugs. These drugs maintain a stable HIF level in the body by inhibiting the HIF-PHD enzyme, thereby promoting the continued expression of erythropoiesis-related genes, and are widely used in the management of renal anemia. Therefore, judging their structural similarity not only depends on the chemical structure itself, but also depends on its consistency in pharmacological classification and target mechanism. Judging from international data, HIF-PHI drugs have common core structural elements, which are usually designed around the chemical skeleton that stabilizes the HIF-α subunit. Therefore, multiple similar drugs have a high degree of structural similarity.

Among them, the drugs with the closest structure to dapodustat include Roxadustat (Roxadustat), Vadadustat, Molidustat, etc. These drugs are all oral small molecule inhibitors of the same target. Their structural design revolves around inhibiting the HIF-PHD enzyme, stabilizing HIF signals and promoting the natural production of erythropoietin (EPO). From the perspective of chemical structure, although each molecule has differences in substituents, side chain morphology, and spatial conformation in order to achieve different pharmacokinetics or safety characteristics, the overall pharmacological framework is consistent and can be regarded as derivatives of similar structures.

Roxadustat is the earliest drug on the market HIF-PHI, its structural and functional groups have similar carboxamide or heterocyclic characteristics to those of daprostat, and both are designed to block the active site of the PHD enzyme. Vadarestat is a newer generation molecule with a highly similar stereochemical arrangement to daporostat and is used to achieve stable blood concentrations and reduce the risk of excessive elevation of EPO. Molistat incorporates a specific amide structure into its structural design to make it more selective and is used in some countries to manage anemia in non-dialysis CKD patients.

Reference materials:https://en.wikipedia.org/wiki/Daprodustat