Selective retinoid

Future generations of such receptor subtype-selective retinoids or also retinobenzoic acids [3] may provide clinicians with more specific and less toxic diugs for dermatologic therapy. 

Chandraratna RAS (1996) Tazarotene first of a new generation of receptor-selective retinoids. Br J Dermatol 135 18-25... 

Yen WC, Corpuz MR, Prudente RY, Cooke TA, Bissonnette RP, Negro-Vilar A, Lamph WW (2004) A selective retinoid X receptor agonist bexarotene (Targretin) prevents and overcomes acquired paclitaxel (Taxol) resistance in human non-small cell lung cancer. Clin Cancer Res 10(24) 8656-8664. 

Nagpal, S. and Chandraratna, R.A., Recent developments in receptor-selective retinoids, Curr. Pharm. Des., 6, 919, 2000. 

Silicon analogues 105b,d of known pan-RAR selective retinoid agonist TTNPB 105a were synthesized from ketones 106 by a Wittig reaction followed by hydrolysis (07CBC1688) (Scheme 19). 

Of 70 patients with cutaneous T cell lymphomas, three who were taking gemfibrozil had to have it withdrawn because of increases in serum concentrations of triglycerides and bexarotene, an RXR-selective retinoid rexi-noid , which is used for all stages of cutaneous T cell lymphoma (6). 

The short and efficient stereospecific synthesis of the dimer-selective retinoid X receptor modulator was carried out in the laboratory of L.G. Hamann. The synthetic sequence began with the von Pechmann reaction between tetramethyltetrahydronaphthol and ethyl acetoacetate in 75% sulfuric acid solution. The desired coumarin was formed regioselectively and isolated in high yield. 

Hamann, L. G. An Efficient, Stereospecific Synthesis of the Dimer-Selective Retinoid X Receptor Modulator (2E,4E,6Z)-7-[5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2- (n-propyloxy)naphthalen-3-yl]-3- methylocta-2,4,6-trienoic Acid. J. Org. Chem. 2000, 65, 3233-3235. 

As discussed in a previous section, the systemic and topical toxicity, as well as the teratogenicity of retinoids, limits the clinical usefulness of these compounds. The general opinion of both basic scientists and clinicians is that these toxicities may be mitigated by the development of receptor subtype-selective retinoids. Although this may ultimately be proven to be true, there is currently little factual basis for this opinion, at least with respect to the RAR subtypes, because it has been quite difficult to separate clinical efficacy from toxicity. Nonetheless, this remains a noble goal in the continued development of receptor sub-type-selective retinoids. 

Tretinoin binds primarily to the RAR-a receptors. Alitretinoin is considered a panagonist that is, it binds to all known retinoid receptors, producing diverse regulatory effects. Bexarotene is synthetic and is classed as a rexinoid. It is the first RXR-selective retinoid agonist. The exact mechanism of action of alitretinoin and bexarotene as anticancer agents is unknown. ... 

Leibowitz, M.D., Ardecky, R.J. and Boehm, M.F. (2006) Biological characterization of a heterodimer-selective retinoid X receptor modulator potential benefits for the treatment of type 2 diabetes. Endocrinology, 147, 1044-1053. 

Chandraratna, R.A. (1998) Rational design of receptor-selective retinoids. Journal of the American Academy of Dermatology, 39 (4 Pt 2), S124—S128. 

C. M., Goldman, M.E. and Heyman, R.A. (1994) Synthesis and structure-activity relationships of novel retinoid X receptor-selective retinoids. Journal of Medicinal Chemistry, 37, 2930-2941. 

CYP26 expression in normal human tracheobronchial epithelial cells was compared with that in human lung carcinoma cell lines (Kim et al. 2000). CYP26 mRNA could be induced by the retinoic acid receptor-selective retinoid 4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthracenyl)-benzoic acid but not by the retinoid X receptor-selective retinoid SRI 1217 or the anti-activator-protein 1-selective retinoid SRI 1302. Retinoic acid receptor a-, P, and y-selective retinoids were able to induce CYP26 this induction was inhibited by the retinoic acid receptora-selective antagonist Ro41-5253. The induction of CYP26 correlated with increased biotransformation of retinoic acid into 18-hydroxy-, 4-OXO-, and 4-hydroxy-retinoic acid. 

Preclinical and Clinical Toxicology of Selected Retinoids Jerome J. Kamm, Kathleen O. Ashenfelter, and Carl W. Ehmann... 

Table 1 Light Absorbances of Selected Retinoids Barua and Furr ... 

Acute Toxicity of Selected Retinoids in Laboratory Animals... 

II. Clinical Toxicology of Selected Retinoids A. Retinol Toxicity in Humans... 

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