Molidustat
Molidustat is an HIF stabilizer being developed by Bayer as part of clinical trials for the treatment of patients with anemia caused by kidney disease. However, development has been discontinued.
Structural formula of molidustat
Molar mass 314.309 g/mol, molecular formula C13H14N8O2
Report from Pharmazeutische Zeitung online dated October 9, 2013:
"A Phase IIb study program is currently being initiated for the treatment of cardio-renal syndrome with the new active ingredient molidustat in patients with anemia and concomitant chronic kidney disease and/or end-stage renal failure. Molidustat is an inhibitor of the enzyme hypoxia-inducible factor prolyl hydroxylase (HIF-PH), which stimulates the production of erythropoietin (EPO) and the formation of red blood cells. According to Bayer, results from Phase I studies demonstrate that the inhibition of HIF-PH by molidustat leads to increased endogenous production of EPO."
It was approved in Japan in January 2021 under the name Musredo (Bayer Yakuhin) for the oral treatment of anemia resulting from chronic kidney disease (CKD).
Relevance to Doping
Due to the effect of molidustat, whereby endogenous EPO production is stimulated by inhibiting HIF, the substance could also be of interest to athletes and be misused. By stimulating increased EPO production, more red blood cells (erythrocytes) are formed, thereby enabling improved oxygen uptake and transport capacity. Consequently, endurance performance can be enhanced.
The active ingredient molidustat was therefore specifically banned for the first time on January 1, 2017, by the World Anti-Doping Agency (WADA) under Group S2: Peptide Hormones, Growth Factors, Related Compounds, and Mimetics. According to the Prohibited List, however, the active ingredient was already prohibited prior to this date without being listed by name, as it is a related compound to HIF stabilizers and can still be classified as a non-approved active ingredient (Group S0).
Detection of Doping
A corresponding mass spectrometric method for the detection of molidustat was developed and published in 2016.
Dib J, Mongongu C, Buisson C, Molina A, Schänzer W, Thuss U, Thevis M. Mass spectrometric characterization of the hypoxia-inducible factor (HIF) stabilizer drug candidate BAY 85-3934 (molidustat) and its glucuronidated metabolite BAY-348, and their implementation into routine doping controls. Drug Test Anal. 2017 Jan;9(1):61-67
According to statistics from WADA-accredited laboratories worldwide, two positive findings involving molidustat were reported for the year 2017.
- See also HIF stabilizers
