Tazarotene selectively binds to retinoic acid receptors RAR-β and RAR-γ, it is the first receptor-selective aromatic retinoid that has effective treatment for psoriasis, hemorrhoids.
Retinoids bind to retinoic acid receptors (RARs) and retinoid X receptors (RXRs) to regulate the expression of genes involved in cell growth and differentiation. Tazarotene is an acetylenic retinoid that can be metabolized by esterase to its active form, tazarotene acid, that acts as a RARb/g specific retinoid. Tazarotene at the dose of 1 μM decreased the proliferation of primary human skin fibroblasts 4 days after the treatment and inhibited the growth rate at day 6. Tazarotene form 0.001 – 10 μM also suppressed BdrU incorporation at a dose-dependent manner and the significant inhibition was found at the doses of 0.1 μM and above. The maximal inhibition of tazarotene on BrdU incorporation was observed at 1 μM, which was 22% that of the control cells, and the IC50 value was 60 nM[5]. Treatment of reconstructed human epidermis tissues with tazarotene (0.1% cream) for 3 days resulted in a loss of keratohyalin granules in the stratum granulosum compared to vehicle-treated cultures. Also, in tazarotene-treated tissues, the kerain 10 expression in the stratum spinosum was lower than that in untreated controls, while the expression of kerain 19 was significantly induced in all viable cell layers. In Rhino mouse model, daily administration of tazarotene (0.1% cream, 7 days) completed (100%) reduced the utricle diameter compared to water- or vehicle-treated animals[6].
作用机制
Tazarotene is a prodrug that can be metabolized into its active free-acid form, tazarotene acid. As a receptor-selective retinoid, it incorporates the double bonds of the retinoic acid polyene chain in two ring structures and a linear triple bond system[7].
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