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Retinoids : An A-Z Guide To Their Biology, Therapeutic Opportunities & Pharmaceutical DevelopmentPublished by: LeadDiscovery Published: Feb. 1, 2003 Table of Contents
AbstractThe retinoids play a key role in differentiation, proliferation and apoptosis and as a result over 30 naturally occurring and synthetic analogs of retinoic acid are now either in development or on the market. Retinoids in current use are effective in only a small number of cancers as well as acne and psoriasis. Extending this benefit to other types of cancer as well as newer indications such as diabetes and airway inflammation has represented a hurdle that will only be fully overcome by taking into account the biology of the retinoids. LeadDiscovery’s "Retinoids: An A-Z guide to their biology, therapeutic opportunities & pharmaceutical development" represents one of the most comprehensive insights into the retinoid field published in recent years. The aim of this report is to bring the reader up to date with advances in this area, pharmaceutical activity relating to retinoid development and strategies that will lead to the identification of improved retinoids.Available retinoids are effective in treating acne and psoriasis. Likewise the retinoids are also beneficial in the treatment of acute promyelocytic leukemia, skin cancer, Kaposi's sarcoma and cutaneous T cell lymphoma. This has led to the launch of Ligand Pharmaceuticals' three marketed retinoids Tagretin gel, Tagretin capsules and Panretin which are indicated for T cell lymphoma or Kaposi's sarcoma. Although the incidence of these cancers is relatively low Ligand's retinoids generated sales of $57 million in 2002. Although numerous cancers are associated with alterations in retinoid biology, clinical efficacy of retinoids has been limited - understanding why, and how this "resistance" can be overcome therefore represents a major goal in oncology. Meeting this goal will extend the therapeutic benefit of the retinoids to other major cancers as well as other newer indications for the retinoids such as diabetes and COPD. These advances would be attractive both clinically and commercially. Early clinical studies and retinoid development commenced without an understanding of retinoid molecular biology. It is now clear that the actions of these molecules are, in almost all cases, via their nuclear receptors, whereby they are able to impinge on the expression of multiple genes. It is therefore not surprising that a "shotgun" approach to the retinoids has generally produced disappointing results in the clinic. "Retinoids : An A-Z guide to their biology, therapeutic opportunities & pharmaceutical development" takes the reader on a journey through the various field of retinoid biology and is designed to offer an insight into how the retinoids confer specificity under physiological conditions; the pathophysiology of the retinoids; and pharmaceutical strategies that may increase the therapeutic benefits of the retinoids. In particular the report overviews
The make-up of a particular dimer not only determines which genes it can influence, but it also determines which of the many co-regulatory molecules it may bind. Paralleling the "histone code" the large number of possible dimer/co-regulatory complexes adds a further level of plasticity, through what has been termed the "co-factor code". Challenges of the future will include the selection of gene targets and the identification of dimer-co-regulatory complex(es) that play a role in the control of these genes. This report provides a full inventory of known co-regulatory molecules. Advances in genomics are allowing gene expression profiles to be identified for particular disease states and gene targeting is already aiding the drug development process. It is now hoped that the identification of dimer/co-regulatory complexes able to regulate the expression of these target genes will soon become a common feature of therapeutic development. Get Full Details About This Report >> |
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