Dermatological agents retinoids

Vitamin A constitutes the most significant sector of the commercial retinoid market and is used primarily in the feed area. In the pharmaceutical area, there are several important therapeutic dermatologic agents which stmcturaHy resemble vitamin A and they are depicted in Figure 2 (see Pharmaceuticals). The carotenoids as provitamin A compounds also represent an important commercial class of compounds with P-carotene [7235-40-7] (10) occupying the central role (Fig. 3) (9). 

Because the skin contains RARa and RARy proteins, with the latter predominating (1 6) [12], research is devoted to establishing the predominant signalling pathway in the skin in order to develop more effective dermatological agents [127]. Yu et al. [59] reported that RARa-selective retinoids had greater potency than RARy-selective retinoids at reducing utricule size in... 

More than 1500 retinoids have been synthesized. Two in particular, 13-cw-retinoic acid (isotretinoin) and etretinate (Figure 38-4), have generated considerable interest as agents for the treatment of dermatological disorders. 13-cA retinoic acid inhibits sebum production, is the drug of choice for treatment of severe cystic acne, and is useful in the treatment of other forms of acne. Etretinate is used in Europe for treatment of psoriasis and related disorders. 

CRA has been detected in humans [34] and was the first RAR-RXR pan-agonist discovered [35-37] and may be classified as a retinoid/rexinoid. It is the only retinoic acid isomer not approved for the common dermatological diseases. However, it has recently been launched in the US as adjuvant topical treatment of AIDS-associated Kaposi s sarcoma [38-41]. This agent is the first RXR ligand to be approved for the treatment of a dermatological disease. In a randomized study with 268 AIDS-associated Kaposi s sarcoma patients, 35% treated with alitretinoin (0.1% gel) had a positive response, compared with 18% treated with vehicle gel irrespective of the number of concurrent antiretroviral therapies [41], 9-CRA is in clinical trials for the treatment of various cancers, including breast cancer [42], renal cell carcinoma [43,44] and squamous cell carcinoma [45—47]. 

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