13-Feb-2004

Emerging Drug Discovery Targets: 6th February

Summary

This edition of "Emerging Drug Discovery Targets" features a potential approach to the treatment of COPD; Ligands' retinoic acid receptor agonist with appetite suppressive and insulin sensitizing properties; the use of HDAC inhibitors for the treatment of rheumatoid arthritis; Tamoxifen as a dual chemopreventative and anti-atherosclerosis treatment; and broad based inhibition of multidrug resistance proteins for improved cancer treatment. As usual we also provide updates on industrial advances a

Last Updated: 27-Aug-2010

Emerging Drug Discovery Targets

from LeadDiscovery

6th February 2004

to view this alert on line please go to http://www.leaddiscovery.co.uk/TherapeuticAdvances%20Archive/Feb%206th%20emerging%20targets.htm

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"Emerging Drug Discovery Targets" provides a twice monthly summary of some of the most exciting breaking information recently featured by the pharmaceutical analysts, LeadDiscovery. Information includes editorials on recently published journal articles, selected press releases and "intelligence reports". Our target audience includes business development personnel, senior management and researchers within the drug development sector as well as bioscience investors and analysts.

Please feel free to pass this mail onto colleagues that may benefit from registration to Emerging Drug Discovery Targets. To register click here.

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In this weeks edition:

Editorial comment on selected journal articles
A fortnight in Drug Development: Advances from industry [more]
Today's breaking scientific publications for the drug development community [more]
This week's licensing opportunities [more]
New DiscoveryDossiers/Chemistry Libraries [more]:
Emerging Drug Discovery Targets archive

Blocking the CXCL10:CXCR3 axis for the treatment of COPD: There is a pressing need to develop new treatments for the chronic obstructive pulmonary diseases (COPD), chronic obstructive bronchitis and emphysema. World-wide, 600 million people suffer from COPD, with some three million dying from the disease each year. This serious healthcare problem is paralleled by a global market of US$2.8 billion. There is a particular need to develop drugs that control the underlying inflammatory and destructive processes that cause COPD as no currently available drug therapy reduces the relentless progression of COPD. In contrast to the enormous advances made in asthma management (see our recent overview of current and future asthma therapeutics) little significant progress has been made in COPD therapeutics. COPD involves a chronic inflammation in small airways and lung parenchyma, with the involvement of numerous inflammatory cells with CD8+ Tc1 type T lymphocytes having been implicated as key culprits in the pathogenesis of disease. New data demonstrate that the levels of CXCL10, a ligand for CXCR3 (both of which have been demonstrated in the peripheral airways of patients with COPD) are increased by 8-fold in the lungs of COPD patients. This study suggests that limiting CXCL10 production represents a target for the treatment of COPD and may be effected through the use of TNF-alpha blocking strategies or by inhibiting NF-kappa B...[more on these findings]

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LG100268 (LG268) as an appetite suppressor and insulin sensitizing agent: Obesity represents a global problem with high associated mortality and co-morbidities, and the world obesity market has been predicted to reach $3.7 billion by 2008. The drive to develop new treatments for obesity is therefore immense. Ghrelin represents one particularly promising breaking targets in the field of obesity prompting LeadDiscovery to produce a DiscoveryDossier analyzing this field (click here for access). Recent targets for the treatment of obesity as well as other metabolic disorders have emerged from the nuclear receptor family (for an analysis of nuclear receptors and the key position that they occupy within the pharmaceutical sector, click here). Examples of nuclear receptors can be found in the retinoic acid and the peroxisome proliferator-activated nuclear receptor (PPAR) sub-families. Readers interested in learning more about the development of retinoid ligands and their role in therapeutics may wish to access LeadDiscovery's dossier Retinoids : An A-Z guide to their biology, therapeutic opportunities & pharmaceutical development (click here for access). In their recent Endocrinology paper Ogilvie et al describe the role that the retinoid receptor RXR plays in energy balance, investigate the mechanisms underlying the novel activities of RXR pathways, and further characterize Ligand Pharmaceutical’s retinoid receptor agonist, LG100268 (LG268)...[more on these findings]

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HDAC inhibitors for the treatment of rheumatoid arthritis: Rheumatoid arthritis is one of the more common autoimmune diseases affecting an estimated 5 million individuals. As described in LeadDiscovery’s state of the art analysis of rheumatoid arthritis drug discovery targets and therapeutic candidates (click here), this field is attracting massive interest in the wake of resurgent R&D activity which has advanced our understanding of the etiology of rheumatoid arthritis. The development of histone deacetylase (HDAC) inhibitors was originally related to their ability to modulate transcriptional activity and hence slow tumor progression (click here to access "Histone deacetylase inhibitors: Redefining pharmaceutical approaches to the treatment of cancer"). There are many similarities between rheumatoid arthritis and cancer and HDAC inhibitors have therefore been linked to a possible approach to rheumatoid arthritis. Chung et al now validate this concept demonstrating that two different HDAC inhibitors dramatically reduce paw swelling in a model of rheumatoid arthritis...[more on these findings]

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Tamoxifen as a dual chemopreventative and anti-atherosclerosis treatment: According to the American Heart Association cardiovascular diseases have been the most common cause of death in the US each year with the exception of 1918. In 1998, this group of diseases claimed the lives of nearly 1 million Americans. Atherosclerosis is common to many cardiovascular diseases and is characterized by arterial wall thickening and loss of elasticity and the formation of plaques that can rupture with consequent thrombosis. Atherosclerosis affected nearly 174 million individuals in the major pharmaceutical markets in 2000. During 2000-2010, total sales of anti-atherosclerosis therapies will grow robustly, to in excess of US$13.7billion by 2008 (click here for an up date of the cardiovascular market). Atherosclerotic plaques consist of accumulated intracellular and extracellular lipids, smooth muscle cells, connective tissue, and glycosaminoglycans. The earliest detectable lesion of atherosclerosis is the fatty streak consisting of lipid-laden foam cells. These cells are macrophages that have migrated as monocytes from the circulation into the subendothelial layer of the intima. A primary lipid found in foam cells is cholesteryl ester, which is formed from cholesterol and long-chain fatty acyl-coenzyme A in the presence of acyl-CoA:cholesterol acetyltransferase (ACAT). In a recent study de Medina et al demonstrated that tamoxifen, an estrogen receptor modulator commonly used in the prevention and treatment of breast cancer (for an analysis of breast cancer therapeutics click here) inhibits ACAT activity at clinically relevant concentrations. This group has conducted SAR studies of tamoxifen and related molecules laying the ground work for the development of new ACAT inhibitors, possibly with additional SERM activity. Such molecules represent likely candidates for the treatment of atherosclerosis and especially so those patients at risk of developing both atherosclerosis and breast cancer...[more on these findings]

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Broad based inhibition of multidrug resistance proteins for improved cancer treatment: An estimated 10 million Americans over the age of 50 years old suffer from osteoporosis and a further 32.9 million have low bone mass, placing them at an increased risk for developing this condition. Patients with these conditions carry an increased risk of sustaining fractures, which are both clinically problematic and costly to healthcare systems, and the development of new osteoporosis treatments therefore offers immense opportunities to the pharmaceutical industry. In a recent DiscoveryDossier we analyze therapeutic and pharmaceutical opportunities in the field of osteoporosis (click here for access). One new molecular target being investigated for the possible treatment of osteoporosis is alpha(v)beta(3) integrin. Researchers from Merck have been actively involved in the rational design of small-molecule alpha(v)beta(3) integrin antagonists and here we highlight their most recent data relating to the optimization of a series of imidazolidinones which has produced a candidate for clinical trials...[more on these findings]

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A fortnight in Drug Development - Our Tour of Industry Press Releases

Key press releases selected from recent editions of the tracking service, DailyUpdates.

Advances in novel approaches towards the treatment of cancer: Caspase inhibitors; gene therapy; monoclonal antibodies; XIAP blockade [more]

New approaches to rheumatoid arthritis [more]

European Regulators Grants Sildenafil Orphan Drug Designation For Pulmonary Arterial Hypertension [more]

New DiscoveryDossiers & PharmaReports:

Thrombosis in Cancer - Expanding Focus for Anticoagulants [more]
Osteoarthritis - COX-2s wear down traditional NSAID use [more]
Monoclonal Antibodies Report 2003: Meeting Clinical and Financial Expectations [more]
World Protein Arrays Markets [more]
Strategic Analysis of World Combinatorial Chemistry Markets [more]
The Market for Bioengineered Protein Drugs [more]
RNAi 2004 [more]
DNA Microarrays and Their Materials [more]
DNA Sequencing and PCR Markets [more]