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Retinoids

Pulmonary, Bone, Vitamins and Autocoid Therapeutic Agents

  1. Marcia I. Dawson

Published Online: 15 SEP 2010

DOI: 10.1002/0471266949.bmc065.pub2

Burger's Medicinal Chemistry and Drug Discovery

Burger's Medicinal Chemistry and Drug Discovery

How to Cite

Dawson, M. I. 2010. Retinoids. Burger's Medicinal Chemistry and Drug Discovery. 369–546.

Author Information

  1. Sanford-Burnham Medical Research Institute, La Jolla, CA

Publication History

  1. Published Online: 15 SEP 2010

Abstract

Retinoid drugs find major applications in the topical treatment of cutaneous proliferative disorders such as acne, psoriasis, and photoaging and cutaneous cancers such as cutaneous T-cell lymphoma (CTCL) and Kaposi's sarcoma. Oral retinoids are successfully used to treat nodular/cystic acne, systemic CTCL, and acute promyelocytic leukemia. This overview of available retinoid drugs and those in the preclinical or clinical pipeline covers their development, indications, clinical trial results, adverse effects, and pharmacology/metabolism. Retinoids have been described historically and functionally in the context of interaction with their nuclear receptors—retinoic acid receptors (RARs) and retinoid X receptors (RXRs)—in inducing gene transcription. RAR-selective retinoids or their prodrugs include first-generation all-trans-retinoic acid (tretinoin) and its 13-cis isomer (isotretinoin), and second-generation acitretin and its ethyl ester (etretinate), both having an aromatic 2,3,6-trimethyl-4-methoxyphenyl terminus. Third-generation more aromatic analogs include ethyl ester tazarotene (Tazorac®) and adapalene (Differin®), both selective for RAR subtypes β and γ, and RARα-selective pipeline candidates Am80 and NRX 195183, which are in clinical trials. RAR and RXR transcriptional panagonist 9-cis-retinoic acid is next and is followed by RXR-selective bexarotene (Targretin™) and two RXR-selective clinical trial candidates, 9cUAB and NRX 194204. The fourth generation includes three compounds that may have applications in the treatment or prevention of cancer. While originally considered as retinoids, such as N-(4-hydroxyphenyl) retinamide, or as retinoid-related or derived, such as ST1926 (AHPC) and SHetA2, they subsequently were found to function independently of the RARs and RXRs in inhibiting cancer cell proliferation and inducing apoptosis.

Keywords:

  • Accutane;
  • 9-cis-retinoic acid;
  • 13-cis-retinoic acid;
  • 3-Cl-AHPC;
  • 9cUAB