Rexinoids

Retinoids and rexinoids Targretin Liver Class comparison, [38]... 

Shirley, M. A., Wheelan, P., Howell, S. R., and Murphy, R. C. (1997). Oxidative metabolism of a rexinoid and rapid phase II metabolite identification by mass spectrometry. Drug Metab. Dispos. 25 1144-1149. 

Martin, G., Poirier, H., Hennuyer, N., Crombie, D., Fruchart, J. C., Heyman, R. A., Besnard, P., and Auwerx, J. (2000). Induction Of The Fatty Acid Transport Protein 1 and Acyl-Coa Synthase Genes by Dimer-Selective Rexinoids Suggests That the Peroxisome Proliferator-Activated Receptor-Retinoid X Receptor Heterodimer is Their Molecular Target./ Bid. Chem. 275, 12612-12618. 

Retinoic X receptors (RXR, a, (3 and " (), also termed rexinoid receptors, are usually classified among orphan receptors, but belong to the thyroid/retinoid family. RXR is an obligatory partner dimerizing with other thyroid/retinoid receptors. RXR selectively bind the 9-cis isomer of retinoic acid, whereas RAR bind aU-tran retinoic acid as well as its 9-cis isomer. RXR selective agonists are termed rexi-noids, like bexarotene used as an antineoplastic in the treatment of cutaneous T-cell lymphoma and the cutaneous lesions of T-cell lymphomas and Kaposi s sarcoma. 

Rigas, J. R., Dragnev, K. H. Emerging role of rexinoids in non-small cell lung cancer focus on bexarotene. Oncologist, 2005, 70(1), 22-33. 

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. ... 

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]. 

Bexarotene (7, Targretin ) is a seledive RXR agonist (classified as a rexinoid) whose exad mechanism of action in cancer therapy and chemoprevention is poorly... 

Development of New Retinoids/Rexinoids and the Future for Retinoid-based Therapies... 

There is now compelling evidence from the number of retinoids in the clinic and in clinical studies (Table 12.1) that these molecules exhibit efficacy in human diseases. The use of ATRA for the treatment of acute promyelocytic leukemia is considered a successful therapy in our view. It is the hope that the application of retinoids, most probably more receptor specific retinoids/rexinoids, in combination with other chemotherapeutic agents, will lead to broad clinical utility in many diseases. We anticipate that the retinoid field will continue to expand as researchers gain more information about new levels of retinoid/rexinoid biology and their relevance to human diseases. 

Tzameli, I., Chua, S. S., Cheskis, B., and Moore, D. D. (2003) Complex effects of rexinoids on ligand dependent activation or inhibition of the xenobiotic receptor, CAR. Nucl. Recept. 1, 2. 

Liby KT, Yore MM, Spom MB (2007) Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer. Nat Rev Cancer 7 357-369... 

---