Ретиноевой кислоты

Описание

all-trans Retinoic acid is a metabolite of vitamin A and a ligand for retinoic acid receptors (RARs) with IC₅₀ values of 9, 3, and 10 nM for RARα, RARβ, and RARγ, respectively, in radioligand binding assays. It induces expression of a luciferase reporter in COS-7 cells expressing RARα, RARβ, or RARγ (EC₅₀s = 169, 9, and 2 nM, respectively). all-trans Retinoic acid (17 nmol) reduces papilloma formation induced by phorbol 12-myristate 13-acetate (TPA; ) in mice. It reduces bile duct proliferation, hydroxyproline levels, and liver inflammation in a rat model of α-naphthylisothiocyanate-induced chronic cholestasis and reduces plasma levels of alkaline phosphatase and bile salts in the Mdr2^-/- mouse model of cholestasis. all-trans Retinoic acid also reduces hepatic fat accumulation, triglycerides, body weight, and serum glucose levels in mice with Western diet-induced obesity.

Химические свойства

Yellow-Orange Powder

Использование

Physiological metabolite of vitamin A. Effects gene expression via nuclear retinoic acid receptors (RAR); mediates cellular growth and differentiation

Показания

Topical tretinoin (Retin-A, Renova, Avita), like isotretinoin, alters keratinization in the acroinfundibulum. In addition, it reverses certain premalignant and other histological changes associated with the photoaging changes that accompany chronic exposure to ultraviolet radiation. Topically applied tretinoin is indicated in comedogenic and papulopustular acne vulgaris, and its mild exfoliative effects make it sometimes useful in molluscum contagiosum, flat warts, and some ichthyotic disorders. It is often prescribed to lessen the clinical signs of photoaging (wrinkling and hyperpigmented macules).

Определение

ChEBI: Retinoic acid is a retinoid in which all four exocyclic double bonds have E- (trans-) geometry. It is a naturally occurring derivative of vitamin A (retinol). Retinoids such as tretinoin are important regulators of cell reproduction, proliferation, and differentiation and are used to treat acne and photodamaged skin and to manage keratinization disorders such as ichthyosis and keratosis follicularis.

Всемирная организация здравоохранения(ВОЗ)

Tretinoin, a retinol derivative, was introduced in 1973 exclusively for the topical treatment of severe acne. Preparations of tretinoin are indicated for topical use only since oral administration has been associated with risk of toxicity from hypervitaminosis-A and subsequently of teratogenicity.

Общее описание

Yellow to light-orange crystalline powder.

Реакции воздуха и воды

Tretinoin may be sensitive to prolonged exposure to air. Insoluble in water.

Профиль реактивности

Tretinoin may discolor on exposure to light. Tretinoin is extremely sensitive to exposure to light and, therefore, Tretinoin should be fully protected from light during all handling. Solutions are unstable in the presence of strong oxidizers. Tretinoin is incompatible with strong oxidizing agents. .

Пожароопасность

Flash point data for Tretinoin are not available; however, Tretinoin is probably combustible.

Биологическая активность

Endogenous agonist for retinoic acid receptors. Also positively modulates PPAR δ receptors (K d = 17 nM). Promotes differentiation of embryonic stem cells (ESCs) into adipocytes, neurons and glia in vitro .

Клиническое использование

The major toxic effect of tretinoin is erythema and irritation of the skin to which it is applied, especially if the skin is moist.This toxicity often decreases with continued therapy.

Профиль безопасности

Poison by ingestion, intraperitoneal, subcutaneous, and intravenous routes. Experimental reproductive effects. Questionable carcinogen with experimental neoplastigenic and teratogenic data. Human mutation data reported. A human skin irritant. When heated to decomposition it emits acrid smoke and irritating fumes. Used to treat acne and other skin problems.

Методы очистки

Purify the acid by chromatography on silicic acid columns, and eluting it with a small amount of EtOH in hexane. Also dissolve it in Et2O, wash it with H2O, dry (Na2SO4), evaporate and the solid residue is recrystallised from MeOH (0.53g /3.5mL MeOH to give 0.14g) or EtOH. It also recrystallises from i-PrOH, or as the methyl ester from MeOH. UV in MeOH has max at 351nm ( 45,000). 9-Cis-acid forms yellow needles from EtOH, with m 189-190o, and its UV in MeOH has max at 343nm ( 36,500); the 13-cis-acid forms red-orange plates from i-PrOH with m 174-175o, and UV has max at 345nm ( 39,800). Store it in the dark, in an inert atmosphere, at 0o [Robeson et al. J Am Chem Soc 77 4111 1955]. [Beilstein 9 IV 2387.]