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Emerging Drug Discovery Targets from LeadDiscovery

16 July 2003 Posted on: 16 Jul 03

Summary

This edition of




TherapeuticAdvances: 16th July 2003




Emerging Drug Discovery Targets


from LeadDiscovery


16 July 2003


**************************************



"Emerging Drug Discovery Targets" provides a summary of some of the most exciting breaking data featured in LeadDiscovery's TherapeuticAdvanceshttp://www.leaddiscovery.co.uk/TherapeuticAdvances%20Archive/170603/index.html">TherapeuticAdvances> service. Please feel free to distribute "Emerging Drug Discovery Targets" to your colleagues or arrange for it to be accessed through your company intranet.


In this weeks edition:






HDAC7: A novel target for autoimmune disorders: Over 50 different autoimmune diseases have been identified, some of which are common (eg rheumatoid arthritis) while other are very rare. According to some analysts, new therapeutic approaches will drive the market for autoimmune disorders to grow at a rate of over 15%, to a value of over $21 billion by 2006.


The regulation of thymocyte survival/death through T-cell receptor (TCR) activation plays a key role in establishing a functional T-cell repertoire. Control over this repertoire prevents the development of autoimmunity while facilitating host defense. The clonal deletion of auto-reactive T cells in thymus is essential for the discrimination between self and non-self and hence immature T cells that recognize self-peptide-MHC complexes with high affinity/avidity are driven towards apoptosis (negative selection). Therapeutics that bolster this negative selection process may be of benefit to patients with diverse autoimmune disorders.


Among the molecules implicated in T-cell apoptosis is Nur77 (also known as NGFI-B or TR3), a member of the orphan nuclear receptor super-family. Nur77 was originally identified as an immediate early gene transiently induced by serum, growth factors and nerve growth factor. It has also been shown that Nur77 and Nor-1, a related member of the Nur77 family, are induced during TCR-mediated apoptosis. Expression of a dominant-negative Nur77 blocks activation-induced cell death in T-cell hybridomas as well as negative selection in transgenic mice. Conversely, transgenic mice that express wild type Nur77 or Nor-1 exhibit massive apoptosis and a reduction in thymocyte numbers.


Post-translational modification of Nur77 has been previously demonstrated thereby introducing a system of control to the process of T cell apoptosis. This is consistent with the observation that expression of Nur77 does not necessarily correlate with induction of apoptosis. This and other studies suggest the existence of a mechanism that inhibits the proapoptotic function of Nur77. The phosphatidylinositol 3-kinase (PI3-K)-Akt pathway is activated in response to TCR activation and is implicated in mediating survival signals in T cells.


More recently it has been demonstrated that transcription can also be regulated by histone plasticity. This phenomenon centers on the now generally accepted view that chromatin structure is plastic and that histone (de)acetylation regulates genome structure and hence expression. Modifying this process by histone deacetylase (HDAC) inhibitors can therefore regulate, potentially in a highly specific manner, transcription. Information relating to histone deacetylation is emerging with breathtaking rapidity with over 1 new article currently being published every day. In response to this activity we recently published a comprehensive dossier of the pharmaceutical potential of HDAC inhibitors (Click'>http://www.leaddiscovery.co.uk/reports/hdac.html">Click here to access).


HDAC7 was first identified as HDAC-D in 1999 and then classified as HDAC7, a member of the class II histone deacetylase family in 2001. Since its discovery, the functional significance of HDAC7 has remained unclear however UCSF researchers have recently taken a major step forward in this respect demonstrating that it is highly expressed in certain thymocytes. Furthermore HDAC7 was shown to inhibit the expression of Nur77 via the transcription factor MEF2D. HDAC7 is exported from the nucleus during T cell receptor activation, leading to Nur77 expression and hence the facilitation of apoptosis. The UCSF group has demonstrated that a mutant HDAC7 that is not exported from the nucleus in response to TCR activation suppresses TCR-mediated apoptosis. On the other hand, inhibition of HDAC7 expression by RNA interference causes increased apoptosis in response to TCR activation. These observations define HDAC7 as a regulator of Nur77 and apoptosis in developing thymocytes and offer excellent proof of concept data to support the development of HDAC7 inhibitors as modulators of the T-cell repertoire. Such inhibitors therefore deserve investigation as candidates for the treatment of autoimmune disorders. One concept described in our HDAC dossier is that specificity may be conferred to HDAC inhibitors by blocking their interaction with binding proteins rather that inhibiting HDAC activity per se. In this respect, molecules able to interfere with HDAC7:MEF2D interactions may be of particular therapeutic benefit. This work is related to licensing opportunities [more'>http://www.leaddiscovery.co.uk/target%20of%20the%20month/hdac.html">more on these findings]


**********************


Syk tyrosine kinase as a target for asthma: Readers of DailyUpdates, our daily tracker for the drug discovery sector (click'>http://www.leaddiscovery.co.uk/PubMed-dailyupdates.html">click here), or indeed anyone who follows advances in the pharmaceutical industry will be aware of major changes occurring in the field of asthma therapeutics. For example, Novartis announced on June 23rd that the novel IgE-blocker Xolair® (Omalizumab) has been approved by the US Food and Drug Administration (FDA) for the treatment of moderate-to-severe persistent asthma in adults and adolescents. At the same time Merck Sharp & Dohme announced that they have agreed to fund Amrad with an upfront payment of $7.4 million, and potentially up to $167 million plus royalties, to advance its early-stage biological treatment for asthma.


This activity is hardly surprising given that the incidence of asthma has dramatically increased over recent years. Furthermore, although currently available treatments are generally effective patient compliance that is currently very poor, especially with respect to inhaled treatment. In addition 5% of patients are unresponsive to these treatments and it is this cohort that accounts for a large segment of asthma related healthcare costs. Novel non-inhaled treatments such as Xolair stand to offer considerable benefit to asthmatics.


Global revenue for 2001 from asthma therapies has been reported by some to be as high as $11.7 billion and up until recently annual growth rates of 10-15% have been reported. Most sources however predict that this level of growth is not sustainable. Competition within the anti-asthmatic market will therefore grow increasingly intense. In response to activity generated by new and emerging asthma therapeutics, the increased need for these treatments, the commercial benefit that they could enjoy and the competition that they will experience, LeadDiscovery has recently produce a state of the art of asthma therapeutics (Click'>http://www.leaddiscovery.co.uk/reports/asthma.html">Click here).


One of the targets analyzed in our asthma dossier is Syk tyrosine kinase. Syk (p72Syk) kinase is a protein tyrosine kinase that plays a pivotal role in high affinity IgE receptor signaling in mast cells. Syk is also involved in antigen receptor signaling of B and T lymphocytes and in eosinophil survival in response to IL-5 and GM-CSF and so Syk inhibitors might have several useful beneficial effects in atopic diseases. Aerosolized Syk antisense oligodeoxynucleotide inhibits allergen-induced inflammation in a rat model, indicating that this may be a target for drug development. Given this proof of concept it is exciting that Bayer researchers have recently identified BAY 61- 3606, a potent (Ki = 7.5 nM) and selective inhibitor of Syk kinase. BAY 61-3606 inhibited not only degranulation (IC50 values between 5-46 nM) but also lipid mediator and cytokine synthesis in mast cells. BAY 61- 3606 was highly efficacious in basophils obtained from healthy human subjects (IC50 = 10 nM) and seems to be at least as potent in basophils obtained from atopic (high serum IgE) subjects (IC50 = 8.1 nM). B cell receptor activation and IgE receptor signaling in eosinophils and monocytes were also potently suppressed by BAY 61-3606. Oral administration of BAY 61-3606 to rats significantly suppressed antigen-induced passive cutaneous anaphylactic reaction, bronchoconstriction, and bronchial edema at 3 mg/kg. Further, BAY 61-3606 attenuated antigen-induced airway inflammation in rats. Based on these anti-inflammatory effects of BAY 61-3606 both in vitro and in vivo, it was demonstrated that Syk might play a very critical role in the pathogenesis of allergic reactions. Further development of BAY 61-3606 is eagerly awaited [more'>http://www.leaddiscovery.co.uk/PubMed/PubMed-Syk-asthma.html">more on these findings]


Readers may be aware of the “Kinase Enterprise library” recently featured by LeadDiscovery. This is a targeted library of candidate kinase inhibitors that is available for in house screening and screening of this library for other inhibitors of Syk may be of immense benefit to companies involved in airway inflammation (Click'>http://www.leaddiscovery.co.uk/reports/Kinase-inhibitors.html">Click here for further information on this library).


**********************


Development of an oncolytic virus targeted to the hypoxic tumor milieu: Cancer continues to drive the identification and development of new therapeutic strategies. LeadDiscovery has focussed on a number of these over recent months. Particularly exciting are the endogenous inhibitors of apoptosis (click'>http://www.leaddiscovery.co.uk/reports/apoptosis.html">click here for more); histone deacetylase inhibitors (accesshttp://www.leaddiscovery.co.uk/reports/hdac.html">access> our recent dossier on this field here); and the retinoids (click'>http://www.leaddiscovery.co.uk/reports/retinoids.html">click here for more). Oncolytic viruses represent a further approach to cancer with considerable potential. Although the cytotoxic effects of viruses are usually viewed in terms of pathogenicity, it is possible to harness this activity for therapeutic purposes. In particular, viral genomes are highly versatile, and can be modified to direct their cytotoxicity towards cancer cells. To our knowledge there are almost 20 such oncolytic virus-based therapeutics in development by the pharma/biotech sector. Although most of these are in preclinical development, therapies from Cell Genesys, Crusade, Medigene and Oncolytics are more advanced.


The use of replication-competent gene therapy viruses, which have a cytolytic cycle, has emerged as a viable strategy to specifically kill tumor cells and enhance adjuvant therapeutic gene transfer by viral spread throughout the tumor. The development of vectors whose replication is dependent upon microenvironmental constraints specific to tumor growth rather than cell-intrinsic gene expression profiles or genetic alterations would be particularly useful.


Hypoxia is an integral component of the tumor microenvironment that develops in most solid tumors regardless of their origin, location, or genetic alterations and arises from the rapid growth of the tumor relative to its vascular supply. Since hypoxia is a major factor in conferring resistance of cancer cells to radio- and chemo-therapies, selecting tumor clones of high malignancy, predisposing tumors to metastasis, the development of novel therapeutic strategies that can target hypoxic areas of tumors is important. Hypoxia-inducible factor (HIF) is a heterodimeric transcription factor that mediates responses to hypoxia by binding to a hypoxia-response element (HRE) present within target genes and the HIF/HRE system can therefore be utilized to specifically target therapeutic gene expression to tumors.


Recently Dawn Post and Erwin Van Meir from Emory University examined the potential use of this system to conditionally regulate the replication of an adenovirus, thereby creating a novel type of oncolytic therapy vector, hypoxia/HIF-dependent replicative adenovirus (HYPR-Ad), that targets cells with activated HIF, such as hypoxic cells. Dependency on hypoxia was brought about by reintroducing E1 genes (this is essential for replication) into a replication deficient virus. The E1A gene was under the regulation of a bi-directional hypoxia/HIF-responsive promotor; the E1B gene was restored with its endogenous regulatory elements. This HYPR-Ad was highly effective at causing cytolysis of human foreskin fibroblasts maintained under hypoxic but not normoxic conditions. In contrast a control virus lacking the hypoxia/HIF-responsive promotor was unable to target hypoxic cells, producing cytolysis independent of oxygen saturation. Consistent with this effect HYPR-Ad was able to effectively kill each member of a panel of brain tumor cells when exposed to hypoxia.


This study and the further development of oncolytic viruses such as HYPR-Ad has immense therapeutic potential not only against tumors that develop a hypoxic environment but also against cancer cells with active HIF under normoxic conditions. Such an approach may be expected to be useful in a wide range of tumors since unlike other therapies efficacy is relatively independent of tumor genotype. In addition cytolytic activity may be expected to be directed against tumor cells as well as adjacent cells which may be important since the neovasculature may be compromised limiting delivery.


Perhaps even more exciting is the possibility of developing HYPR-Ad-like viruses that deliver genes with antitumor properties. Such viruses may be expected to preferentially express such genes in hypoxic tumors conferring specificity. Furthermore if such genes were to inhibit angiogenesis, a situation of synergy may be expected [more'>http://www.leaddiscovery.co.uk/Pubmed/PubMed-oncolytic.html">more on these findings]


**********************


Industry news


This section of Emerging Drug Discovery Targets is undergoing major changes - from now on industry news will feature key press releases delivered via our tracking service, DailyUpdateshttp://www.leaddiscovery.co.uk/PubMed-dailyupdates.html">DailyUpdates>.





New DiscoveryDossiers:



  • Asthma Therapeutics: New treatment options and emerging drug discovery targets [More]http://www.leaddiscovery.co.uk/reports/asthma.html">[More]>
  • Diabetes 2003 [More]http://www.leaddiscovery.co.uk/reports/vg009.html">[More]>
  • Potassium Channel Enterprise library [More]http://www.leaddiscovery.co.uk/reports/Potassium-channels.html">[More]>




TherapeuticAdvances: 16th July 2003




Emerging Drug Discovery Targets


from LeadDiscovery


16 July 2003


**************************************



"Emerging Drug Discovery Targets" provides a summary of some of the most exciting breaking data featured in LeadDiscovery's TherapeuticAdvanceshttp://www.leaddiscovery.co.uk/TherapeuticAdvances%20Archive/170603/index.html">TherapeuticAdvances> service. Please feel free to distribute "Emerging Drug Discovery Targets" to your colleagues or arrange for it to be accessed through your company intranet.


In this weeks edition:






HDAC7: A novel target for autoimmune disorders: Over 50 different autoimmune diseases have been identified, some of which are common (eg rheumatoid arthritis) while other are very rare. According to some analysts, new therapeutic approaches will drive the market for autoimmune disorders to grow at a rate of over 15%, to a value of over $21 billion by 2006.


The regulation of thymocyte survival/death through T-cell receptor (TCR) activation plays a key role in establishing a functional T-cell repertoire. Control over this repertoire prevents the development of autoimmunity while facilitating host defense. The clonal deletion of auto-reactive T cells in thymus is essential for the discrimination between self and non-self and hence immature T cells that recognize self-peptide-MHC complexes with high affinity/avidity are driven towards apoptosis (negative selection). Therapeutics that bolster this negative selection process may be of benefit to patients with diverse autoimmune disorders.


Among the molecules implicated in T-cell apoptosis is Nur77 (also known as NGFI-B or TR3), a member of the orphan nuclear receptor super-family. Nur77 was originally identified as an immediate early gene transiently induced by serum, growth factors and nerve growth factor. It has also been shown that Nur77 and Nor-1, a related member of the Nur77 family, are induced during TCR-mediated apoptosis. Expression of a dominant-negative Nur77 blocks activation-induced cell death in T-cell hybridomas as well as negative selection in transgenic mice. Conversely, transgenic mice that express wild type Nur77 or Nor-1 exhibit massive apoptosis and a reduction in thymocyte numbers.


Post-translational modification of Nur77 has been previously demonstrated thereby introducing a system of control to the process of T cell apoptosis. This is consistent with the observation that expression of Nur77 does not necessarily correlate with induction of apoptosis. This and other studies suggest the existence of a mechanism that inhibits the proapoptotic function of Nur77. The phosphatidylinositol 3-kinase (PI3-K)-Akt pathway is activated in response to TCR activation and is implicated in mediating survival signals in T cells.


More recently it has been demonstrated that transcription can also be regulated by histone plasticity. This phenomenon centers on the now generally accepted view that chromatin structure is plastic and that histone (de)acetylation regulates genome structure and hence expression. Modifying this process by histone deacetylase (HDAC) inhibitors can therefore regulate, potentially in a highly specific manner, transcription. Information relating to histone deacetylation is emerging with breathtaking rapidity with over 1 new article currently being published every day. In response to this activity we recently published a comprehensive dossier of the pharmaceutical potential of HDAC inhibitors (Click'>http://www.leaddiscovery.co.uk/reports/hdac.html">Click here to access).


HDAC7 was first identified as HDAC-D in 1999 and then classified as HDAC7, a member of the class II histone deacetylase family in 2001. Since its discovery, the functional significance of HDAC7 has remained unclear however UCSF researchers have recently taken a major step forward in this respect demonstrating that it is highly expressed in certain thymocytes. Furthermore HDAC7 was shown to inhibit the expression of Nur77 via the transcription factor MEF2D. HDAC7 is exported from the nucleus during T cell receptor activation, leading to Nur77 expression and hence the facilitation of apoptosis. The UCSF group has demonstrated that a mutant HDAC7 that is not exported from the nucleus in response to TCR activation suppresses TCR-mediated apoptosis. On the other hand, inhibition of HDAC7 expression by RNA interference causes increased apoptosis in response to TCR activation. These observations define HDAC7 as a regulator of Nur77 and apoptosis in developing thymocytes and offer excellent proof of concept data to support the development of HDAC7 inhibitors as modulators of the T-cell repertoire. Such inhibitors therefore deserve investigation as candidates for the treatment of autoimmune disorders. One concept described in our HDAC dossier is that specificity may be conferred to HDAC inhibitors by blocking their interaction with binding proteins rather that inhibiting HDAC activity per se. In this respect, molecules able to interfere with HDAC7:MEF2D interactions may be of particular therapeutic benefit. This work is related to licensing opportunities [more'>http://www.leaddiscovery.co.uk/target%20of%20the%20month/hdac.html">more on these findings]


**********************


Syk tyrosine kinase as a target for asthma: Readers of DailyUpdates, our daily tracker for the drug discovery sector (click'>http://www.leaddiscovery.co.uk/PubMed-dailyupdates.html">click here), or indeed anyone who follows advances in the pharmaceutical industry will be aware of major changes occurring in the field of asthma therapeutics. For example, Novartis announced on June 23rd that the novel IgE-blocker Xolair® (Omalizumab) has been approved by the US Food and Drug Administration (FDA) for the treatment of moderate-to-severe persistent asthma in adults and adolescents. At the same time Merck Sharp & Dohme announced that they have agreed to fund Amrad with an upfront payment of $7.4 million, and potentially up to $167 million plus royalties, to advance its early-stage biological treatment for asthma.


This activity is hardly surprising given that the incidence of asthma has dramatically increased over recent years. Furthermore, although currently available treatments are generally effective patient compliance that is currently very poor, especially with respect to inhaled treatment. In addition 5% of patients are unresponsive to these treatments and it is this cohort that accounts for a large segment of asthma related healthcare costs. Novel non-inhaled treatments such as Xolair stand to offer considerable benefit to asthmatics.


Global revenue for 2001 from asthma therapies has been reported by some to be as high as $11.7 billion and up until recently annual growth rates of 10-15% have been reported. Most sources however predict that this level of growth is not sustainable. Competition within the anti-asthmatic market will therefore grow increasingly intense. In response to activity generated by new and emerging asthma therapeutics, the increased need for these treatments, the commercial benefit that they could enjoy and the competition that they will experience, LeadDiscovery has recently produce a state of the art of asthma therapeutics (Click'>http://www.leaddiscovery.co.uk/reports/asthma.html">Click here).


One of the targets analyzed in our asthma dossier is Syk tyrosine kinase. Syk (p72Syk) kinase is a protein tyrosine kinase that plays a pivotal role in high affinity IgE receptor signaling in mast cells. Syk is also involved in antigen receptor signaling of B and T lymphocytes and in eosinophil survival in response to IL-5 and GM-CSF and so Syk inhibitors might have several useful beneficial effects in atopic diseases. Aerosolized Syk antisense oligodeoxynucleotide inhibits allergen-induced inflammation in a rat model, indicating that this may be a target for drug development. Given this proof of concept it is exciting that Bayer researchers have recently identified BAY 61- 3606, a potent (Ki = 7.5 nM) and selective inhibitor of Syk kinase. BAY 61-3606 inhibited not only degranulation (IC50 values between 5-46 nM) but also lipid mediator and cytokine synthesis in mast cells. BAY 61- 3606 was highly efficacious in basophils obtained from healthy human subjects (IC50 = 10 nM) and seems to be at least as potent in basophils obtained from atopic (high serum IgE) subjects (IC50 = 8.1 nM). B cell receptor activation and IgE receptor signaling in eosinophils and monocytes were also potently suppressed by BAY 61-3606. Oral administration of BAY 61-3606 to rats significantly suppressed antigen-induced passive cutaneous anaphylactic reaction, bronchoconstriction, and bronchial edema at 3 mg/kg. Further, BAY 61-3606 attenuated antigen-induced airway inflammation in rats. Based on these anti-inflammatory effects of BAY 61-3606 both in vitro and in vivo, it was demonstrated that Syk might play a very critical role in the pathogenesis of allergic reactions. Further development of BAY 61-3606 is eagerly awaited [more'>http://www.leaddiscovery.co.uk/PubMed/PubMed-Syk-asthma.html">more on these findings]


Readers may be aware of the “Kinase Enterprise library” recently featured by LeadDiscovery. This is a targeted library of candidate kinase inhibitors that is available for in house screening and screening of this library for other inhibitors of Syk may be of immense benefit to companies involved in airway inflammation (Click'>http://www.leaddiscovery.co.uk/reports/Kinase-inhibitors.html">Click here for further information on this library).


**********************


Development of an oncolytic virus targeted to the hypoxic tumor milieu: Cancer continues to drive the identification and development of new therapeutic strategies. LeadDiscovery has focussed on a number of these over recent months. Particularly exciting are the endogenous inhibitors of apoptosis (click'>http://www.leaddiscovery.co.uk/reports/apoptosis.html">click here for more); histone deacetylase inhibitors (accesshttp://www.leaddiscovery.co.uk/reports/hdac.html">access> our recent dossier on this field here); and the retinoids (click'>http://www.leaddiscovery.co.uk/reports/retinoids.html">click here for more). Oncolytic viruses represent a further approach to cancer with considerable potential. Although the cytotoxic effects of viruses are usually viewed in terms of pathogenicity, it is possible to harness this activity for therapeutic purposes. In particular, viral genomes are highly versatile, and can be modified to direct their cytotoxicity towards cancer cells. To our knowledge there are almost 20 such oncolytic virus-based therapeutics in development by the pharma/biotech sector. Although most of these are in preclinical development, therapies from Cell Genesys, Crusade, Medigene and Oncolytics are more advanced.


The use of replication-competent gene therapy viruses, which have a cytolytic cycle, has emerged as a viable strategy to specifically kill tumor cells and enhance adjuvant therapeutic gene transfer by viral spread throughout the tumor. The development of vectors whose replication is dependent upon microenvironmental constraints specific to tumor growth rather than cell-intrinsic gene expression profiles or genetic alterations would be particularly useful.


Hypoxia is an integral component of the tumor microenvironment that develops in most solid tumors regardless of their origin, location, or genetic alterations and arises from the rapid growth of the tumor relative to its vascular supply. Since hypoxia is a major factor in conferring resistance of cancer cells to radio- and chemo-therapies, selecting tumor clones of high malignancy, predisposing tumors to metastasis, the development of novel therapeutic strategies that can target hypoxic areas of tumors is important. Hypoxia-inducible factor (HIF) is a heterodimeric transcription factor that mediates responses to hypoxia by binding to a hypoxia-response element (HRE) present within target genes and the HIF/HRE system can therefore be utilized to specifically target therapeutic gene expression to tumors.


Recently Dawn Post and Erwin Van Meir from Emory University examined the potential use of this system to conditionally regulate the replication of an adenovirus, thereby creating a novel type of oncolytic therapy vector, hypoxia/HIF-dependent replicative adenovirus (HYPR-Ad), that targets cells with activated HIF, such as hypoxic cells. Dependency on hypoxia was brought about by reintroducing E1 genes (this is essential for replication) into a replication deficient virus. The E1A gene was under the regulation of a bi-directional hypoxia/HIF-responsive promotor; the E1B gene was restored with its endogenous regulatory elements. This HYPR-Ad was highly effective at causing cytolysis of human foreskin fibroblasts maintained under hypoxic but not normoxic conditions. In contrast a control virus lacking the hypoxia/HIF-responsive promotor was unable to target hypoxic cells, producing cytolysis independent of oxygen saturation. Consistent with this effect HYPR-Ad was able to effectively kill each member of a panel of brain tumor cells when exposed to hypoxia.


This study and the further development of oncolytic viruses such as HYPR-Ad has immense therapeutic potential not only against tumors that develop a hypoxic environment but also against cancer cells with active HIF under normoxic conditions. Such an approach may be expected to be useful in a wide range of tumors since unlike other therapies efficacy is relatively independent of tumor genotype. In addition cytolytic activity may be expected to be directed against tumor cells as well as adjacent cells which may be important since the neovasculature may be compromised limiting delivery.


Perhaps even more exciting is the possibility of developing HYPR-Ad-like viruses that deliver genes with antitumor properties. Such viruses may be expected to preferentially express such genes in hypoxic tumors conferring specificity. Furthermore if such genes were to inhibit angiogenesis, a situation of synergy may be expected [more'>http://www.leaddiscovery.co.uk/Pubmed/PubMed-oncolytic.html">more on these findings]


**********************


Industry news


This section of Emerging Drug Discovery Targets is undergoing major changes - from now on industry news will feature key press releases delivered via our tracking service, DailyUpdateshttp://www.leaddiscovery.co.uk/PubMed-dailyupdates.html">DailyUpdates>.





New DiscoveryDossiers:



  • Asthma Therapeutics: New treatment options and emerging drug discovery targets [More]http://www.leaddiscovery.co.uk/reports/asthma.html">[More]>
  • Diabetes 2003 [More]http://www.leaddiscovery.co.uk/reports/vg009.html">[More]>
  • Potassium Channel Enterprise library [More]http://www.leaddiscovery.co.uk/reports/Potassium-channels.html">[More]>

LeadDiscovery

Last updated on: 27/08/2010 11:40:18

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