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General Description:

Vadadustat, identified by CAS number 1000025-07-9, is a notable compound with significant therapeutic applications. One of the most common symptoms of advanced renal disease is anemia, caused primarily by the inability of the kidney to respond to anemic conditions with a corresponding increase in (EPO) production. Treatment of anemia of chronic kidney disease (CKD) has traditionally involved the administration of exogenous erythropoiesis-stimulating agents (ESAs), such as , to counter the decrease in endogenous EPO production. While efficacious, the overuse of ESAs has been associated with cardiovascular complications, progression of CKD, and increases in overall mortality. A relatively new and alternative treatment option for patients with anemia of CKD are small molecule inhibitors of hypoxia-inducible factor prolyl-hydroxylase (HIF-PH). These agents inhibit prolyl-hydroxylase domain oxygen sensors, which essentially mimics hypoxic conditions and activates hypoxia-inducible factor, a transcription factor that serves a multitude of roles, including the stimulation erythropoiesis. Vadadustat is an orally administered inhibitor of hypoxia-inducible factor prolyl-hydroxylase (HIF-PH) which is currently approved in Japan for the treatment for anemia due to CKD in both dialysis-dependent and non-dialysis dependent adult patients, and is currently awaiting a regulatory decision by the FDA for the same indication. The safety and efficacy of vadadustat have been shown to be non-inferior to darbepoetin alfa in patients with anemia of CKD undergoing dialysis, but it did not meet the prespecified noninferiority criterion for cardiovascular safety in a similar study in patients with non-dialysis-dependent CKD.

Mechanism of Action:

Vadadustat functions by: Hypoxia-inducible factors (HIFs) are transcription factors responsible for cellular survival under hypoxic conditions. They regulate a number of processes including angiogenesis, cell growth and differentiation, various metabolic processes, and erythropoiesis. Under normoxic conditions, HIF is degraded via hydroxylation by prolyl-hydroxylase domain (PHD) dioxygenases. Vadadustat is an inhibitor of HIF-PHDs that facilitates increased HIF activity in the absence of hypoxic conditions. In patients with anemia of chronic kidney disease, in whom normal erythropoiesis is dysfunctional, this stimulates the production of erythropoietin and subsequent correction of anemia. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Classification:

Vadadustat belongs to the class of organic compounds known as n-acyl-alpha amino acids. These are compounds containing an alpha amino acid which bears an acyl group at its terminal nitrogen atom, classified under the direct parent group N-acyl-alpha amino acids. This compound is a part of the Organic compounds, falling under the Organic acids and derivatives superclass, and categorized within the Carboxylic acids and derivatives class, specifically within the Amino acids, peptides, and analogues subclass.

Categories:

Vadadustat is categorized under the following therapeutic classes: Amino Acids, Amino Acids, Peptides, and Proteins, Antianemic Preparations, Blood and Blood Forming Organs, Pyridines. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.