生物活性

• 描述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].

• 动物研究
  剂量	Rat: 0.1 mg/kg - 3 mg/kg[3] (p.o.) Mice: 10 mg/kg[4] (i.p.)
  给药途径	p.o., i.p.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02620813	Acne Vulgaris	Phase 4	Recruiting	May 2019	United States, California ... more >> Dermatology Research Area Recruiting Davis, California, United States, 95616 Contact: Negar Foolad, MAS    916-734-1509    nfoolad@ucdavis.edu    Contact: Lauren A Hassoun, BS    916-734-6550    lahassoun@ucdavis.edu    Principal Investigator: Raja K Sivamani, MD          UC Davis Department of Dermatology Recruiting Sacramento, California, United States, 95816 Contact: Raja Sivamani, MD       rajasivamani@gmail.com Collapse <<
  NCT02045277	Plaque Psoriasis	Phase 2	Completed	-	United States, California ... more >> Valeant Site 13 Encino, California, United States, 91436 Valeant Site 11 San Diego, California, United States, 92123 Valeant Site 15 Santa Rosa, California, United States, 95403 United States, Georgia Valeant Site 10 Augusta, Georgia, United States, 30909 Valeant Site 09 Newnan, Georgia, United States, 30263 United States, Kentucky Valeant Site 08 Louisville, Kentucky, United States, 40217 United States, Maryland Valeant Site 04 Rockville, Maryland, United States, 20850 United States, Michigan Valeant Site 14 Clinton Township, Michigan, United States, 48038 United States, Minnesota Valeant Site 07 Fridley, Minnesota, United States, 55432 United States, New Jersey Valeant Site 01 East Windsor, New Jersey, United States, 08520 United States, New York Valeant Site 03 New York, New York, United States, 10075 Valeant Site 17 Rochester, New York, United States, 14623 United States, North Carolina Valeant Site 02 High Point, North Carolina, United States, 27262 United States, Texas Valeant Site 05 Austin, Texas, United States, 78759 Valeant Site 06 College Station, Texas, United States, 77845 United States, Utah Valeant Site 16 Salt Lake City, Utah, United States, 84117 United States, Virginia Valeant Site 18 Lynchburg, Virginia, United States, 24501 Valeant Site 12 Norfolk, Virginia, United States, 23507 Collapse <<
  NCT01000714	Mild to Moderate Psoriasis	Phase 2	Completed	-	Israel ... more >> Clalit Health care Tel-Aviv, Israel, 63564 Collapse <<

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• 参考文献

• [1] Talpur R, Cox K, et al. Efficacy and safety of topical tazarotene: a review. Expert Opin Drug Metab Toxicol. 2009 Feb;5(2):195-210.

  [2] Nagpal S, Thacher SM, et al. Negative regulation of two hyperproliferative keratinocyte differentiation markers by a retinoic acid receptor-specific retinoid: insight into the mechanism of retinoid action in psoriasis. Cell Growth Differ. 1996 Dec;7(12):1783-91.

  [3] Tazarotene, a Retinoic Acid Receptor (RAR) Agonist, Protects Photoreceptor in a Blue Light–Induced Retinal Degeneratio Model

  [4] Al Haj Zen A, Nawrot DA, et al. The Retinoid Agonist Tazarotene Promotes Angiogenesis and Wound Healing. Mol Ther. 2016 Oct;24(10):1745-1759.

  [5] Ogawa A, Maeguchi M, Uchida Y, Yoshioka T, Kawashima M, Muraki T. Effect of tazarotene, an acetylenic retinoid, on human dermal fibroblast. Jpn J Pharmacol. 1998 Mar;76(3):317-9.

  [6] Hsia E, Johnston MJ, Houlden RJ, Chern WH, Hofland HE. Effects of topically applied acitretin in reconstructed human epidermis and the rhino mouse. J Invest Dermatol. 2008 Jan;128(1):125-30.

  [7] Chandraratna RA. Tazarotene--first of a new generation of receptor-selective retinoids. Br J Dermatol. 1996 Oct;135 Suppl 49:18-25.

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