4-oxo Isotretinoin

4-oxo Isotretinoin is an active metabolite of the retinoid isotretinoin .¹ It is formed from isotretinoin by several cytochrome P450 (CYP450) isoforms, including CYP3A, CYP2B6, and CYP2C19.² 4-oxo Isotretinoin (10 µM) increases protein expression of cytokeratin 7 (CK7) and CK19 in normal human epidermal keratinocytes.³ It inhibits proliferation of retinoid-sensitive UM-SCC-22A and UM-SCC-35 head and neck squamous cell carcinoma (HNSCC) cells in a concentration-dependent manner.⁴ 4-oxo Isotretinoin has been found in influent and effluent wastewater.⁵ It is teratogenic to mouse embryos when administered to pregnant dams at a dose of 100 mg/kg on day 11 of gestation.⁶

1.Colburn, W.A., Vane, F.M., and Shorter, H.J.Pharmacokinetics of isotretinoin and its major blood metabolite following a single oral dose to manEur. J. Clin. Pharmacol.24(5)689-694(1983) 2.Sonawane, P., Cho, H.E., Tagde, A., et al.Metabolic characteristics of 13-cis-retinoic acid (isotretinoin) and anti-tumour activity of the 13-cis-retinoic acid metabolite 4-oxo-13-cis-retinoic acid in neuroblastomaBr. J. Pharmacol.171(23)5330-5344(2014) 3.Baron, J.M., Heise, R., Blaner, W.S., et al.Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitroJ. Invest. Dermatol.125(1)143-153(2005) 4.Klaassen, I., Brakenhoff, R.H., Smeets, S.J., et al.Metabolism and growth inhibition of four retinoids in head and neck squamous normal and malignant cellsBr. J. Cancer85(4)630-635(2001) 5.Yeung, K.W.Y., Zhou, G.-J., HilscherovÁ, K., et al.Current understanding of potential ecological risks of retinoic acids and their metabolites in aquatic environmentsEnviron. Int.136105464(2020) 6.Kochhar, D.M., and Penner, J.D.Developmental effects of isotretinoin and 4-oxo-isotretinoin: The role of metabolism in teratogenicityTeratology36(1)67-75(1987)