Cytochrome P450 family 26 (Retinoic acid-metabolizing enzymes) (CYP26)

Retinoic acid-metabolizing enzymes, primarily the Cytochrome P450 family 26 (comprising CYP26A1, CYP26B1, and CYP26C1), are the principal enzymes responsible for the oxidative catabolism of all-trans retinoic acid (atRA) into inactive or less active polar metabolites (UniProt: P48417, Q9NR63). By regulating the local concentration of atRA, these enzymes control the activation of retinoic acid receptors (RARs), which is essential for normal embryonic development, tissue homeostasis, and cell differentiation (PMID: 11514582). In several pathological conditions, such as certain leukemias and solid tumors, the overexpression of CYP26 enzymes leads to a localized deficiency of atRA, which prevents cellular maturation and promotes tumor progression (PMID: 24510544). Consequently, these enzymes have become significant therapeutic targets for Retinoic Acid Metabolism Blocking Agents (RAMBAs), such as liarozole and talarozole, which aim to elevate endogenous atRA levels to induce differentiation in cancer and dermatological diseases like psoriasis. However, because of the critical role of retinoic acid gradients in morphogenesis, pharmacological inhibition of these enzymes carries a high risk of teratogenicity and other retinoid-related toxicities (PMID: 15135303).

Other names

Retinoic acid hydroxylaseP450RAICYP26A1CYP26B1CYP26C1RAMBA targetsRetinoic acid 4-hydroxylase

Inhibition of the oxidative catabolism of all-trans retinoic acid (atRA) by CYP26 enzymes, thereby increasing endogenous atRA levels and enhancing retinoic acid receptor (RAR) mediated gene transcription (PMID: 24510544).