Oxymetholone

Oxymetholone acts by inducing hematopoietic stem and progenitor cell proliferation in Fanconi anemia. Chronic administration of oxymetholone to aged Fancd2-/- mice significantly improved bone marrow cellularity, corrected red cell macrocytosis, and alleviated peripheral pancytopenia. RNA-Seq transcriptional analysis revealed that oxymetholone suppressed osteopontin (Spp1) transcription by more than ten-fold in HSPCs, identifying osteopontin downregulation as a key molecular mechanism underlying the drug’s proliferative effect on stem cells. Cell cycle analysis by flow cytometry confirmed that oxymetholone profoundly reduced the quiescent G0 fraction of KSL cells and increased the percentage of actively cycling cells in both Fancd2-/- and wild-type mice, without affecting more differentiated lineage-positive cells. Unlike previous hypotheses, oxymetholone did not increase telomerase expression or erythropoietin signaling.

Fig. 1 Oxymetholone suppresses Spp1 transcription through the mediation of AR. (Zhang Q S.; et al. 2015)

Oxymetholone was explored for its ability to form new solid forms and host-guest inclusion complexes with β-cyclodextrin. Recrystallization of oxymetholone in various solvents yielded two polymorphs and one acetic acid solvate, with crystal structures elucidated by single-crystal X-ray diffraction. Oxymetholone also successfully formed a new oxymetholone-β-cyclodextrin inclusion complex, confirmed by powder X-ray diffraction, DSC/TGA thermal analysis, and FT-IR spectroscopy.

Fig. 2 The asymmetric unit of Oxy-2. (Borodi G.; et al. 2024)