TherapeuticAdvances is up-dated twice-monthly highlighting 100's novel projects ready for development and commercialization.

To view the 2002 Therapeutic Advances Archive click here! - for the 2004 listings click here!

January-December 2003

Target of the Month:  

• Janus tyrosine kinase 3 inhibition for the prevention of transplant rejection

• NVP-LAQ824 a novel histone deacetylase inhibitor

• Cx43 as a target for improved wound healing

• Development of GSK-3 inhibitors by GlaxoSmithKline and by Johnson & Johnson

• HDAC7: A novel target for autoimmune disorders

• Ki-67 as a target for anticancer strategies

• Successful gene therapy of pulmonary hypertension

• MAPK/ERK-kinase inhibitors as a promising strategy for the treatment of neuropathic pain

• Retinoids as candidate targets for alzheimer’s disease treatment

• PI3K inhibitors: Targeting multiple tumor progression pathways

• Gap junctions: The future of cancer therapy and prevention?

• Advances in Kv1.3 channel research

• Sigma(1) agonists offer hope to Alzheimer’s disease patients

Target "Lifestyle"

• BAY 41-2272: A novel guanylate cyclase activator for the treatment of erectile dysfunction

• Expanding the therapeutic benefit of sildenafil to the treatment of premature ejaculation 

• Oxytocin as a treatment of erectile dysfunction

• Stimulation of angiogenesis as an approach to erectile dysfunction

• The effect of PDE5 inhibition on patients with stable angina

Focus on Airway disease:  

• Effects of Phosphodiesterase 4 (PDE4) inhibition on host defense

• PDE4D: A target for the treatment of airway hyper-responsiveness in asthma

• IDEC-152 as a candidate treatment of asthma

• AWD 12-281, a PDE4 inhibitor with low emetic potential

• Syk tyrosine kinase as a target for asthma

• Suplatast tosilate: Anti-asthma properties

• Targeting NKT cells for the treatment of asthma

• The role of VEGF in emphysema

• Improved PDE4 inhibitors

• Potential benefits of retinoid treatment to COPD sufferers

• A small molecule inhibitor of VLA-4 for the treatment of allergic airway disease

• Treating corticosteroid resistant airway disease

• Steroid treatment of COPD: relationship to MMP-9

• Targeting phosphodiesterases for the treatment of pulmonary hypertension

Focus on Oncology:  

• Targeting oncolytic viruses to colorectal tumors

• Increasing the anticancer efficacy of docetaxel by ERK inhibitors

• Advances in the development of histone deacetylase inhibitors

• siRNA blocking CXCR4 expression limits metastasis

• Development of an oncolytic virus targeted to the hypoxic tumor milieu

• Leptin and its role in tumor progression

• Cpd 5, a novel Cdc25A inhibitor with anticancer activi

• Aurora2 inhibitors for the treatment of cancer

• Oncolytic viruses as a means of improving radiation therapy

• ATN-161, and integrin antagonists that reduces angiogenesis and tumor progression

• Reintroducing retinoid sensitivity to breast cancer cells

• A-161906 a TGF-beta-like agonist that acts via histone deacetylase inhibition

• Advances in anticancer retinoids

• Combined use of histone deacetylase and methylation inhibitors for improved tumor control

Focus on CardioVascular disease:

• PDE5 inhibition as a treatment of pulmonary hypertension

• The involvement of PDE4D in stroke

• Targeting PDE5 for the treatment of pulmonary hypertension

• Targeted delivery of thrombolytics to newly formed thrombi

• Lithium as a treatment for stroke

• A stable preparation of PGI2 as an effective treatment of stroke

• Recombinant VEGF improves angina

• HO-1 as a target for ischemic disease

• SSR69071: A highly potent elastase inhibitor

• Further benefits of targeting angiotensin for the prevention of stroke

• RWJ-58259 a PAR-1 antagonist with antithrombotic activity

• FGF-4 gene transfer as a treatment of limb ischemia

• Fractalkine:CX3CR1 binding as a target for coronary artery disease

Focus on Metabolic Diseases:

• Alpha(v)beta(3) integrin antagonism as a treatment of osteoporosis

• 11beta-hydroxysteroid dehydrogenase inhibition reduces insulin resistance

• Stimulating Munc1-13 as a means of increasing insulin release

• Stearoyl-CoA desaturase (SCD) as a target for diabetes

• Bone hypoxia: A contributor to bone fracture

• Kv1.3 potassium channels as targets for the treatment of obesity

• Treatments for pulmonary hypertension

• A novel target for osteoporosis

• NO and NMDA in the control of osteoclast function

• Mitofusin 2: a regulator of energy expenditure that contributes to the development of obesity

• Targeting RXR receptors for the treatment of diabetes and obesity

• Matrix metalloproteinases, an emerging target for obesity

• Neuropeptide Y involvement in insulin resistance

• JNK1 as a promising target for obesity, diabetes and insulin resistance

Focus on Immunology & Inflammatory disease:

• FR167653, a candidate p38 MAPK inhibitor for the treatment of rheumatoid arthritis

• VEGFR-1 as a target for rheumatoid arthritis therapies

• Blocking Tie-2 as a treatment of rheumatoid arthritis

• Ribozyme technology as an effective approach to HBV infection

• Kv1.3 potassium channel blockade as an immunomodulatory strategy

• FTY720 as a treatment for multiple sclerosis

• A pilot trial of SCH55700, a humanized monoclonal antibody to IL-5

• The role of p-glycoprotein in intestinal damage

• IL-2 antibodies as an effective treatment of ulcerative colitis

• Clinical potential of retinoid RAR antagonists in arthritis

• SangStat’s RDP58 as a novel anti-inflammatory

• TNF anti-sense oligonucleotides for the treatment of chronic inflammation

• T-614 induces bone formation offering improved treatment of rheumatoid arthritis

Focus on infectious disease:  

• Advances in the treatment of HSV-1 infection

• Mechanisms underlying the respiratory symptomology of RSV infection

• P-glycoprotein inhibitors as adjuvants to antimicrobials

• Optimizing ribozyme therapeutics

• E5564: An emerging treatment of sepsis

• CS-758, an antifungal with activity in fluconazole-resistant candidiasis 

• Advances in infectious disease

• Gene silencing as an approach to HIV infection

Focus on Pain

• 5-HT3 receptor antagonists as analgesics

• T-type Ca2+ channel involvement in visceral pain

• Cannabinoid receptor ligands in the treament of pain

• HSV transfer of Glial cell-derived neurotrophic factor (GDNF) as a treatment of pain

• F 13640, a novel candidate analgesic

• A potent VR1 receptor antagonist blocks inflammatory and neuropathic pain

• F 13640, an exciting candidate analgesic

• H3 agonists as prophylactic treatments of migraine

• Newron’s NW-1029, a candidate for inflammatory and neuropathic pain

• Postsynaptic density protein-95 (PSD-95) as a target for neuropathic pain

• NaV1.8, a sodium channel target for the treatment of chronic pain

• Nociceptin:ORL-1 as a target for analgesia

• The involvement of 5-HT1B/1D receptors in trigeminal pain pathways

Focus on CNS Disease: 

• Novel corticotropin-releasing factor (CRF) receptor antagonists as effective anxiolytics

• Efficacy of the mixed 5-HT2 antagonist/SSRI, nefadozone in Parkinson’s disease

• RS-1259, a dual inhibitor of AChE and SERT for treating Alzheimers disease

• CB2 receptor agonists with anagesic activity

• Development of highly potent inhibitors of the cannabinoid transporter

• Muscarinic receptor activation reduces Abeta1-42 in Alzheimer’s disease

• Induction of NGF as a treatment of Alzheimer’s disease

• Astrocytes as a target for Alzheimers disease therapeutics

• GSK-3 in the etiology of schizophrenia

• Increasing central leptin levels reduces obesity

• Effects of ghrelin on memory and behavior

• Targeting the Inhibitor of Apoptosis family for the treatment of neurodegenerative disorders

• Further evidence linking GSK-3 to Alzheimer’s disease

• Advances in Alzheimer’s disease vaccine therapy

Focus on Angiogenesis: 

• Bisphosphonates as inhibitors of tumor angiogenesis

• Mutual regulation of angiogenesis and adipogenesis

• Combined radiation/SU11248 therapy for the treatment of cancer

• Arteriogenesis as a treatment of stroke

• Angiostatin gene transfer as an approach to the treatment of metastatic liver cancer

• An alpha(1)beta(1) integrin antagonist with anticancer activity

• RNAi technology for the development of improved VEGF therapeutics

• Small molecule antagonists of FGF tyrosine kinase receptor binding

• CD146, a target for the inhibition of angiogenesis

• Phenylacetate-bisphosphonate as a new anticancer candidate

• Dual inhibition of Rho kinase and matrix metalloproteinases offers effective approach to cancer

• Cannabinoid agonists as anticancer agents

• Stem cell treatment of myocardial infarction

• Endorepellin, a novel anticancer target

Focus on Cell Death:

• Mechanisms of apoptosis in Alzheimers disease

• Protein kinase C delta (PKC delta) inhibitors as a target for pro-apoptotic treatment of cancer

• CD271, a retinoid with potential for the treatment of colon cancer

• High throughput screening for stimulators of apoptosis

• ARMER, a novel regulator of apoptosis

• Ketotifen widens the therapeutic window of doxorubicin

• Retinoids as inhibitors of I-kappaB kinase (IKK)

• Pro-apoptotic effects of retinoid like molecules

• XIAP inhibitors as treatments for hormone resistant prostate cancer

• KRN5500 induces apoptosis in leukemia cells

• Histone deacetylase involvement in neuroprotection

• Histone deacetylase regulates survivin expression and apoptosis

• Lipoxygenase inhibitors as treatments of pancreatic cancer

• Reintroducing apoptosis into cancer cells by inhibiting specific tyrosine kinase activity

Licensing Opportunities/Patent Update:  

• ED-71: a vitamin D analogue with bone selective activity

• ONT-093: A P-glycoprotein inhibitor for use in patients with cancer, chronic pain, epilepsy and HIV infection

Focus on industrial development:  

• Strategies for improving high throughput screening

• Axokine: Phase II and III studies demonstrating anti-obesity efficacy

• Tryptase TC30, a novel target for influenza therapeutics

• Non-peptidic protein tyrosine phosphatase inhibitors

• Biochemical and pharmacological characterization of SSR69071, a novel orally active elastase inhibitor.

• Key advances in the development of glycogen synthase kinase-3 (GSK-3) inhibitors

• Targeting growth factors to prevent ischemic cell death following stroke

• Novel inhibitors of VEGFR-2 and VEGFR-3 kinase

• CXCR2 antagonism as an approach to rheumatoid arthritis

• Small molecule inhibition of caspase 3/7 as a treatment of cardiovascular disease