Retinoid biological activity

Bexarotene is a member of a subclass of retinoids that selectively activate rehnoid X receptors (RXRs). These retinoid receptors have biologic activity distinct from that of rehnoic acid receptors (RARs). After oral administration bexarotene is rapidly absorbed. Bexarotene is thought to be eliminated primarily through the hepatobiliary system. It is approved for the treatment of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy. Adverse events possibly related to treatment are lipid abnormalities, hypothyroidism, rash, and blood dyscrasias. 

Retinoids They influence a wide variety of biological activities including cellular proliferation, cellular differentiation, immune function, inflammation, e.g. tretinoin, isotretinoin, etretinate. 

Vitamin A (retinol, 6.1) is the parent of a range of compounds known as retinoids, which possess the biological activity of vitamin A. In general, animal foods provide preformed vitamin A as retinyl esters (e.g. 6.5, which are easily hydrolysed in the gastrointestinal tract) while plant foods provide precursors of vitamin A, i.e. carotenoids. Only carotenoids with a /3-ionone ring (e.g. /1-carotene) can serve as vitamin A precursors. /3-Carotene (6.6)... 

Active-A term originally used to indicate whether a given retinoid showed biological activity as a vitamin in humans. More properly used to describe such activity in any species, order or phylum. 

Vitamins are essential nutrients, which must be supplied exogenously. They are organic compounds with indispensable biological activities as coenzymes in a multitude of cellular metabolic processes. Vitamin A, retinoids (vitamin A-derivatives), carotenoids, vitamin D, vitamin E, and vitamin K are fat-soluble, vitamin C and vitamins of the B-complex are water-soluble. This is of importance for gastrointestinal absorption in oral supplementation as well as the transdermal penetration for topical applications. 

Roalsvig, X, Honeyman, J.A., Tortola-Ni, D.R., Reczek, P. R., Mansuri, M.M., Starrett, J.E., Jr. Retinoic acid receptor beta,gamma-selective ligands synthesis and biological activity of 6-substituted 2-naphthoic add retinoids. J. Med. Chem. 

Oxoretinol is synthesized from canthaxin (see Figure 2.2) and occurs in plasma. It binds to the retinoic acid nuclear receptor (but not the RXR) and is active in tissue differentiation. In the early embryo, the main biologically active retinoid is 4-oxoretinaldehyde, which both activates RARs and also acts as a precursor of oxo-retinoic acid and oxoretinol. 

The term vitamin A currently is applied to compounds posse.s.sing biological activity like that of retinol. The term vilamiii Ai refers to all-/ i .v-retinol. The term retinoid is applied to retinol and its naturally occurring derivatives plus synthetic analogues, which need not have vitamin A activity. 

Some isomers of trans-RA have been reported to exert very potent biological effects. Most noteworthy of these is 9-cis-RA (see Fig. 7,2), which was originally demonstrated to be a retinoid that activates both RARs and RXRs, whereas trans-RA activates only RAR family members (32-34). Levin and colleagues originally isolated [ H]9-cis-RA using RXRs to "trap it in cells fed [ Hl nzres-RA, implying... 

Fig. 1. The structures of key retinoids and their precursors. Fish convert retinyl esters (e.g. retinyl palmitate (RP)) and carotenoids (e.g. /3-carotene) to retinol in the gut lumen prior to intestinal absorption. Retinyl esters (e.g. RP) stored in the liver are synthesized from retinol by lecithin retinol acyltransferase (LRAT) and acyl CoAiretinol acyltransferase (ARAT). The retinyl esters are mobilized through their conversion to retinol by retinyl ester hydrolase (REH), which is then transported in the circulation to various sites in the body. Retinol is further metabolized within specific tissues to retinal by alcohol dehydrogenases (ADH) or short-chain dehydrogenase/reductase. Retinal is converted to the two major biologically active forms of retinoic acid (RA) (all-trans and 9-cis RA). Retinaldehyde dehydrogenase 2 (Raldh2) synthesizes all-trans RA from all-trans precursors and 9-cis RA form 9-cis precursors.

Natural and synthetic compounds with vitamin A activity and inactive synthetic analogues of vitamin A are collectively termed retinoids. The most biologically active. 

Asato, A.E., Peng, A., Hossain, M.Z., Mirzadegan, T., and Bertram, J.S., Azulenic retinoids. Novel nonbenzenoid aromatic retinoids with anticancer activity, 7. Med. Chem., 36, 3137, 1993. Hashizume, H., Ito, H., Kanaya, N., Nagashima, H., Usui, H., Oshima, R., Kanao, M., Tomoda, H., Sunazuka, T., Nagamitsu, T., Kumagai, H., and Omura, S., Synthesis and biological activities of new HMG-CoA synthase inhibitors. 2-Oxetanones with a side chain containing biphenyl, terphenyl or phenylpyridine. Heterocycles, 38, 1551, 1994. 

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