SciBX: Science-Business eXchange Contents: July 11 2013, Volume 6 / Issue 26

TABLE OF CONTENTS July 11 2013, Volume 6 / Issue 26 Analysis Cover Story Translational Notes Targets and Mechanisms Tools The Distillery: Therapeutics Cancer Endocrine/metabolic disease Infectious disease Neurology Ophthalmic disease Various The Distillery: Techniques Disease models Drug platforms SciBX Collections Macrocycles and constrained peptides This special collection explores the factors behind the growing interest in macrocycles and constrained peptides over the last five years and their effect on drug discovery.  Click here to access the collection for free! Produced with support from: Aileron Therapeutics, Inc., Polypeptide Group, Polyphor LTD., Lanthiopharma B.V.   Analysis Cover Story Top Debugging Crohn's disease Benjamin Boettner doi:10.1038/scibx.2013.644 University of Nantes Angers Le Mans researchers have used mannosides to directly target adherent-invasive Escherichia coli, which cause intestinal inflammation in Crohn's disease. The team is planning to test this alternative to standard-of-care TNF-lowering therapies in a mouse model for chronic CD. Full Text | PDF Translational Notes Top Translational tidbits Lev Osherovich and Michael J. Haas doi:10.1038/scibx.2013.645 Last month's public-private partnership with the highest total funding was the launch of the Global Health Innovative Technology Fund, a $100 million infectious disease initiative. On the biotech side, Onyx formed an alliance with UCSF's Helen Diller Family Comprehensive Cancer Center. Full Text | PDF Targets and Mechanisms Top Targeting TB persistence Lauren Martz doi:10.1038/scibx.2013.646 Researchers from California and New York reported a small molecule with activity against nonreplicating and drug-resistant Mycobacterium tuberculosis. The compound, which inhibits two biosynthetic enzymes, could be combined with existing TB drugs to shorten treatment duration and prevent the emergence of resistance. Full Text | PDF Tools Top Attenuating attrition C. Simone Fishburn doi:10.1038/scibx.2013.647 High drug attrition rates from poor clinical safety have spawned numerous in silico optimization algorithms for molecule design, but none has emerged as a true game changer. AstraZeneca and Roche are pooling their data via an intermediary company, MedChemica, to produce a new set of design rules. Full Text | PDF Distillery: Therapeutics Cancer Top Fatty acid binding protein 5 psoriasis-associated (FABP5; EFABP) doi:10.1038/scibx.2013.648 In vitro and mouse studies suggest FABP5 inhibition could help treat breast cancer. Full Text | PDF PTEN (MMAC1; TEP1); phosphoinositide 3-kinase (PI3K) doi:10.1038/scibx.2013.649 Cell culture and mouse studies identified a secreted variant of PTEN that could help treat cancer. Full Text | PDF Ras; rho guanine nucleotide exchange factors (ARHGEFs; GEFs) doi:10.1038/scibx.2013.650 An in vitro study suggests prolonged inhibition of interactions between Ras and GEFs could help treat cancer. Full Text | PDF Tubulin doi:10.1038/scibx.2013.651 Mouse studies suggest conjugates of paclitaxel and β-cyclodextrin polyrotaxane polymers could help treat cancer and have improved safety profiles. Full Text | PDF MAP kinase interacting serine-threonine kinase 1 (MKNK1; MNK1); MKNK2 (MNK2); eukaryotic translation initiation factor 4E (eIF4E) doi:10.1038/scibx.2013.652 In vitro and mouse studies suggest inhibiting MNK1 and MNK2 could help treat the blast crisis phase of CML by reducing eIF4E activation. Full Text | PDF Deoxythymidylate kinase (DTYMK); serine/threonine kinase 11 (STK11; LKB1) doi:10.1038/scibx.2013.653 Cell culture studies suggest inhibiting DTYMK could help treat LKB1 mutant lung cancer. Full Text | PDF DNA doi:10.1038/scibx.2013.654 Mouse and cell culture studies suggest decreasing extracellular DNA levels could help prevent pancreatic cancer metastasis. Full Text | PDF Endocrine/metabolic disease Top Peptidylprolyl cis-trans isomerase NIMA-interacting 4 (PIN4; PAR14) doi:10.1038/scibx.2013.655 Cell culture and mouse studies suggest increasing PIN4 expression could help treat diabetes. Full Text | PDF Infectious disease Top Unknown doi:10.1038/scibx.2013.656 In vitro studies identified small molecule inhibitors of trans-translation that could help treat bacterial infections. Full Text | PDF Ebola glycoprotein GP1 doi:10.1038/scibx.2013.657 Studies in primates suggest rabies (RABV)-based vaccine vectors expressing GP1 could be used to prevent Ebola infection. Full Text | PDF Influenza A virus hemagglutinin (HA) doi:10.1038/scibx.2013.658 Mouse and ferret studies suggest an adeno-associated virus 9 vector that expresses the broadly neutralizing mAb FI6 (AAV9FI6) could be used to prevent influenza infection. Full Text | PDF Influenza A virus hemagglutinin (HA) doi:10.1038/scibx.2013.659 Mouse studies suggest an adeno-associated virus (AAV) 2/8 vector that expresses a broadly neutralizing mAb against HA could help prevent influenza infection. Full Text | PDF Endothelial protein C receptor (EPCR) doi:10.1038/scibx.2013.660 In vitro and cell culture studies suggest disrupting the interaction between Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) and EPCR could help prevent severe malaria. Full Text | PDF Neurology Top Neuropeptide S receptor 1 (NPSR1; NPSR) doi:10.1038/scibx.2013.661 Rat studies suggest the NPSR antagonist NCGC84 could help treat alcoholism. Full Text | PDF β-Site APP-cleaving enzyme 1 (BACE1) doi:10.1038/scibx.2013.662 Rodent studies identified a BACE1 inhibitor that could help treat AD. Full Text | PDF Mitogen-activated protein kinase kinase kinase 11 (MAP3K11; MLK3) doi:10.1038/scibx.2013.663 Cell culture and mouse studies suggest the MLK3 inhibitor URMC-099 could be used to treat HIV-associated neurocognitive disorders (HAND). Full Text | PDF Brain-derived neurotrophic factor (BDNF); noggin (NOG) doi:10.1038/scibx.2013.664 Rodent and primate studies suggest overexpression of BDNF and NOG could help treat HD. Full Text | PDF Nerve growth factor (NGF); tumor necrosis factor receptor 1 (TNFRSF1A; TNFR1; CD120a); tumor necrosis factor-α (TNF-α) doi:10.1038/scibx.2013.665 In vitro and mouse studies suggest activating membrane-tethered TNF-α could help promote nerve repair following injury. Full Text | PDF Ophthalmic disease Top Cannabinoid CB1 receptor (CNR1); CNR2 doi:10.1038/scibx.2013.666 In vitro and rat studies identified CNR1 and CNR2 agonist prodrugs that could help treat glaucoma. Full Text | PDF Various Top Variability in response to cholesterol enriched atherogenic diet (DIET1); fibroblast growth factor 19 (FGF19) doi:10.1038/scibx.2013.667 Mouse studies suggest inhibiting DIET1 could help treat atherosclerosis or hyperlipidemia. Full Text | PDF Sphingosine 1-phosphate receptor 2 (S1PR2; S1P2; EDG5) doi:10.1038/scibx.2013.668 Mouse studies suggest inhibitors of S1PR2 could help treat inflammatory vascular disorders. Full Text | PDF Distillery: Techniques Disease models Top Intestinal organoid model for cystic fibrosis transmembrane conductance regulator (CFTR) function doi:10.1038/scibx.2013.669 An intestinal organoid model for CFTR function could help develop compounds to treat cystic fibrosis. Full Text | PDF Optogenetic models for obsessive compulsive disorder (OCD) in mice doi:10.1038/scibx.2013.670 Mouse studies suggest optogenetic control of brain activity could be useful for studying OCD. Full Text | PDF Drug platforms Top Cow-derived antibody scaffolds doi:10.1038/scibx.2013.671 Structural analysis of bovine complementarity-determining regions (CDRs) could guide the development of new antibody libraries. Full Text | PDF Mammalian cell–based antigen display screening platform doi:10.1038/scibx.2013.672 A mammalian platform for surface antigen display could be used to screen for and discover therapeutic antibodies. Full Text | PDF Top Advertisement 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.

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