Ciclopirox-d11 (sodium salt) (Synonyms: HOE 296b-d11)

Ciclopirox-d11 (sodium salt) is intended for use as an internal standard for the quantification of ciclopirox by GC- or LC-MS. Ciclopirox is an iron chelator, antifungal, and anticancer agent.1,2,3,4 It inhibits the iron-dependent enzyme prolyl hydroxylase 2 (PHD2; IC50 = 1.58 μM), an effect that is reduced in the presence of iron.1 It stabilizes hypoxia-inducible factor-α (HIF-1α) under normoxic conditions in rat glomus cells when used at a concentration of 5 μM.5 Ciclopirox is active against clinical isolates of T. rubrum, T. mentagrophytes, and C. albicans (MICs = 0.03-0.5, 0.03-0.5, and 0.06-0.5 μg/ml, respectively) and inhibits growth of T. mentagrophytes on porcine skin ex vivo when applied topically.2,3 It inhibits proliferation of Rh30, HT-29, and MDA-MB-231 cells in a concentration-dependent manner and halts the cell cycle at the G1/G0 phase and induces apoptosis in Rh30 cells.4 Ciclopirox (25 mg/kg) reduces tumor growth in an MDA-MB-231 mouse xenograft model. Formulations containing ciclopirox have been used in the topical treatment of fungal infections.

|1. Aowicki, D., and Huczynski, A. Structure and antimicrobial properties of monensin A and its derivatives: Summary of the achievements. Biomed. Res. Int. 2013:742149, (2013).|2. Jo Siu, W.J., Tatsumi, Y., Senda, H., et al. Comparison of in vitro antifungal activities of efinaconazole and currently available antifungal agents against a variety of pathogenic fungi associated with onychomycosis. Antimicrob. Agents Chemother. 57(4), 1610-1616 (2013).|3. Ceschin-Roques, C.G., H•nel, H., Pruja-Bougaret, S.M., et al. Ciclopirox nail lacquer 8%: In vivo penetration into and through nails and in vitro effect on pig skin. Skin Pharmacol. 4(2), 89-94 (1991).|4. Zhou, H., Shen, T., Luo, Y., et al. The antitumor activity of the fungicide ciclopirox. Int. J. Cancer 127(10), 2467-2477 (2010).|5. Baby, S.M., Roy, A., Mokashi, A.M., et al. Effects of hypoxia and intracellular iron chelation on hypoxia-inducible factor-1α and -1β in the rat carotid body and glomus cells. Histochem. Cell. Biol. 120(5), 343-352 (2003).