SciBX: Science-Business eXchange Contents: August 8 2013, Volume 6 / Issue 30

TABLE OF CONTENTS August 8 2013, Volume 6 / Issue 30 Analysis Cover Story Targets and Mechanisms Tools The Distillery: Therapeutics Cancer Cardiovascular disease Gastrointestinal disease Infectious disease Neurology Ophthalmic disease Various The Distillery: Techniques Assays and screens Disease models Drug platforms Imaging Markers Advertisement Biopharma Dealmakers A supplement to Nature Biotechnology and Nature Reviews Drug Discovery  The June 2013 issue of Biopharma Dealmakers showcases companies with partnering opportunities. This week, find out about how you can collaborate with Gallus BioPharmaceuticals. Nature Publishing Group and Relay Technology Management present: The Epigenetics Target Explorer  Click here to access this free online tool and the accompanying article in Nature Reviews Drug Discovery.   Analysis Cover Story Top Engaging drug discovery Amy Donner doi:10.1038/scibx.2013.778 Determining whether a compound binds its intended target is a fundamental question in drug discovery, but assays for measuring target engagement in vivo can be indirect. A Swedish group has remedied the situation with a new assay and founded a biotech, Pelago, to optimize the technology. Full Text | PDF Targets and Mechanisms Top PTC readthrough Chris Cain doi:10.1038/scibx.2013.779 There is ample evidence that PTC Therapeutics' ataluren promotes premature stop codon readthrough in vivo, but University of Dundee researchers have found that the DMD and CF compound has no activity in some in vitro assays. Full Text | PDF CRACking pancreatitis Lev Osherovich doi:10.1038/scibx.2013.780 Companies pursuing CRAC inhibitors for immunological disorders have a new indication to consider—acute pancreatitis. Findings from Cardiff University show that CRACs play a central role in the condition. Full Text | PDF Tools Top A new wave of arrhythmia assays C. Simone Fishburn doi:10.1038/scibx.2013.781 Although the race is on to select and validate new preclinical assays that the FDA will accept as replacements for current tests to predict a molecule's arrhythmia potential, the field continues to make even newer breakthroughs. The end result could be personalized cardiotoxicity testing suited to specific patient subpopulations. Full Text | PDF Distillery: Therapeutics Cancer Top Not applicable doi:10.1038/scibx.2013.782 Rat studies suggest convection-enhanced delivery (CED) of brain-penetrant nanoparticles loaded with dithiazanine iodide could help treat glioblastoma multiforme (GBM). Full Text | PDF Tumor necrosis factor-α (TNF-α) doi:10.1038/scibx.2013.783 Mouse studies suggest mAbs that target the transmembrane form of TNF-α could help treat breast cancer. Full Text | PDF MicroRNA-21 (miR-21) doi:10.1038/scibx.2013.784 In vitro and mouse studies suggest inhibiting miR-21 could help treat cancer. Full Text | PDF Not applicable doi:10.1038/scibx.2013.785 Mouse studies suggest inhibiting the formation of neutrophil extracellular traps (NETs) could help prevent cancer metastasis after surgery. Full Text | PDF Telomeric repeat binding factor 2 (TERF2) doi:10.1038/scibx.2013.786 Mouse and patient sample studies suggest inhibiting TERF2 could help treat cancer by promoting the recruitment of NK cells. Full Text | PDF Aurora kinase A (AURKA; Aurora-A); AURKB (Aurora-B) doi:10.1038/scibx.2013.787 In vitro and mouse studies suggest furanopyrimidine-based dual AURKA and AURKB inhibitors could help treat cancer. Full Text | PDF Tet methylcytosine dioxygenase 1 (TET1) doi:10.1038/scibx.2013.788 Studies in patient samples and in mice suggest inhibiting TET1 could help treat mixed lineage leukemia (MLL). Full Text | PDF Protein tyrosine phosphatase 1B (PTP-1B: PTPN1); insulin-like growth factor-1 receptor (IGF1R; CD221) doi:10.1038/scibx.2013.789 Cell culture studies suggest PTP-1B could help treat IGF1R-dependent ovarian cancer. Full Text | PDF Adrenergic receptor β2 (ADRB2); ADRB3; muscarinic acetylcholine receptor M1 (CHRM1; HM1) doi:10.1038/scibx.2013.790 Mouse studies suggest inhibiting autonomic nerve development in the tumor microenvironment could help treat and prevent prostate cancer. Full Text | PDF Androgen receptor (AR); clusterin (CLU; APOJ) doi:10.1038/scibx.2013.791 Cell culture and mouse studies suggest dual inhibition of AR and CLU can delay progression of castration-resistant prostate cancer (CRPC). Full Text | PDF VEGF; VEGF receptor 1 (FLT1; VEGFR-1); VEGFR-2 (KDR/Flk-1) doi:10.1038/scibx.2013.792 A mouse study suggests prolonged anti-VEGF therapy to treat cancer could compromise endocrine function of the thyroid gland. Full Text | PDF Cardiovascular disease Top Adenosine A2B receptor (ADORA2B) doi:10.1038/scibx.2013.793 Patient sample and mouse studies suggest agonizing ADORA2B could help prevent ischemia and reperfusion injury during liver transplant. Full Text | PDF Gastrointestinal disease Top Free fatty acid receptor 2 (FFAR2; GPR43) doi:10.1038/scibx.2013.794 Mouse studies suggest short-chain fatty acid supplementation could be useful for treating colitis and other inflammation-associated colon diseases. Full Text | PDF Infectious disease Top Angiopoietin 2 (ANG2; ANGPT2) doi:10.1038/scibx.2013.795 Mouse studies suggest inhibiting ANG2 could help treat sepsis. Full Text | PDF IL-20 receptor-β (IL20R2; IL20RB) doi:10.1038/scibx.2013.796 Mouse and cell culture studies suggest inhibiting IL20RB could help treat methicillin-resistant Staphylococcus aureus (MRSA) skin infections. Full Text | PDF Neurology Top Serine/threonine kinase 4 (STK4); superoxide dismutase 1 (SOD1) doi:10.1038/scibx.2013.797 Human tissue and mouse studies suggest STK4 inhibitors could help treat ALS. Full Text | PDF Huntingtin (HTT); microRNA-196a (miR-196a) doi:10.1038/scibx.2013.798 Mouse and cell culture studies suggest miR-196a could help treat HD. Full Text | PDF Scavenger receptor class B member 2 (SCARB2) doi:10.1038/scibx.2013.799 Cell culture and rat studies suggest SCARB2 could help treat nerve damage. Full Text | PDF Acid-sensing ion channel-3 (ASIC3; ACCN3) doi:10.1038/scibx.2013.800 In vitro and mouse studies suggest a peptide inhibitor of ASIC3 could help treat inflammatory and acid-induced pain. Full Text | PDF Ophthalmic disease Top Cysteine-rich angiogenic inducer 61 (CYR61; CCN1) doi:10.1038/scibx.2013.801 Patient and mouse studies suggest targeting CCN1 and its degradation products could help treat proliferative diabetic retinopathy. Full Text | PDF Various Top c-Src tyrosine kinase (CSK) doi:10.1038/scibx.2013.802 Mouse studies suggest activating CSK could help treat colitis and colon cancer. Full Text | PDF Distillery: Techniques Assays and screens Top Assay for profiling kinase inhibitor–target interaction in cells doi:10.1038/scibx.2013.803 In vitro and cell culture studies suggest an assay for monitoring kinase inhibitor–sensitive chaperone-kinase interactions could help identify targets of kinase inhibitors in cells. Full Text | PDF Measuring target engagement in samples doi:10.1038/scibx.2013.804 An assay to detect ligand binding in cells could be used to assess target engagement during preclinical and clinical drug development. Full Text | PDF Disease models Top Cellular model for Down syndrome doi:10.1038/scibx.2013.805 A cellular model for trisomy 21 Down syndrome could be useful for studying disease pathophysiology and could help guide the development of new therapeutics. Full Text | PDF Drug platforms Top Crystal structures of Middle East respiratory syndrome coronavirus (MERS-CoV) spike protein doi:10.1038/scibx.2013.806 Crystal structures of the MERS-CoV spike protein in complex with its receptor could aid the development of therapeutics and vaccines against the disease. Full Text | PDF Escherichia coli coculture for making bispecific antibodies doi:10.1038/scibx.2013.807 An E. coli coculture method could be used to make bispecific antibodies. Full Text | PDF Inhibiting recycling pathways to enhance cellular retention of lipid nanoparticle (LNP)-delivered small interfering RNAs doi:10.1038/scibx.2013.808 Inhibiting exocytosis of LNP-delivered siRNAs from endosomes could enhance their retention within the cell. Full Text | PDF Imaging Top Glucose chemical exchange saturation transfer (glucoCEST) to image enhanced glucose uptake in tumor tissues doi:10.1038/scibx.2013.809 Mouse studies suggest the glucoCEST imaging method could help diagnose cancer in a noninvasive manner without needing radioactive tracers. Full Text | PDF Imaging to quantify lipid nanoparticle (LNP)-mediated delivery of small interfering RNAs doi:10.1038/scibx.2013.810 Combination of high-resolution light and electron microscopy (EM) could be used to quantify uptake and trafficking of LNP-delivered siRNAs. Full Text | PDF Markers Top Monitoring conformational variants of α-synuclein (SNCA) to classify neurodegenerative diseases doi:10.1038/scibx.2013.811 Distinct conformational variants of SNCA could be useful as biomarkers for distinguishing between subtypes of neurodegenerative diseases including Parkinson's disease (PD). Full Text | PDF Top

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