SciBX: Science-Business eXchange Contents: November 7 2013, Volume 6 / Issue 43

TABLE OF CONTENTS November 7 2013, Volume 6 / Issue 43 Analysis Cover Story Translational Notes Targets and Mechanisms Tools The Distillery: Therapeutics Autoimmune disease Cancer Cardiovascular disease Gastrointestinal disease Infectious disease Inflammation Neurology Various The Distillery: Techniques Assays and screens Computational models Disease models Drug delivery Drug platforms Markers 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 ALS antisense oligonucleotides Lauren Martz doi:10.1038/scibx.2013.1210 Isis and three academic groups are developing antisense oligonucleotide therapeutics for the most common cause of ALS. The drugs target hexanucleotide repeat expansions in C9orf72 and mitigate neurotoxicity in vitro. Animal models are not yet available. Full Text | PDF Translational Notes Top Translational tidbits Kai-Jye Lou and Lev Osherovich doi:10.1038/scibx.2013.1211 The Cancer Prevention & Research Institute of Texas is back in the grant-making business, GlaxoSmithKline picks academic projects for drug screening collaborations, and a roundup of public-private partnerships. Full Text | PDF Targets and Mechanisms Top Pulse my heart Amy Donner doi:10.1038/scibx.2013.1212 VEGF-A to repair post–myocardial infarction heart damage has stumbled in the clinic because of delivery issues. Now, a multinational team thinks it has solved the delivery problem by using synthetic RNA. The molecule is partnered with Moderna and AstraZeneca. Full Text | PDF Tools Top Phenotypic screening on target Lev Osherovich doi:10.1038/scibx.2013.1213 A Stanford-UCSF team has fished out a new class of NAMPT inhibitor using a phenotypic screen coupled with an shRNA-based target identification system. The method could have broad applicability in matching hits to targets. Full Text | PDF Distillery: Therapeutics Autoimmune disease Top Muscarinic acetylcholine receptor (CHRM; HM) doi:10.1038/scibx.2013.1214 In vitro and mouse studies suggest CHRM antagonists could help treat MS. Full Text | PDF Cancer Top Aurora kinases; polo-like kinase 1 (PLK1; STPK13) doi:10.1038/scibx.2013.1215 Mouse and cell culture studies suggest inhibiting aurora kinases or PLK1 could help treat sonic hedgehog homolog (SHH)-associated medulloblastoma. Full Text | PDF Solute carrier family 7 member 11 cystine glutamate transporter (SLC7A11; xCT) doi:10.1038/scibx.2013.1216 In vitro and mouse studies suggest xCT inhibitors could help treat a subset of triple-negative breast cancers. Full Text | PDF Checkpoint kinase 1 (CHK1); protein CIP2A (KIAA1524; CIP2A) doi:10.1038/scibx.2013.1217 Studies in human tumor samples and cell lines suggest CIP2A levels could help predict the efficacy of CHK1 inhibitors in cancer. Full Text | PDF Heparan sulfate glycosaminoglycan (HSGAG) doi:10.1038/scibx.2013.1218 Cell culture studies suggest inhibiting HSGAG-dependent exosome uptake by noncancerous cells could help prevent exosome-mediated tumor development. Full Text | PDF Topoisomerase I (TOP1) doi:10.1038/scibx.2013.1219 In vitro and mouse studies suggest fluorinated camptothecin could be used to treat cancer. Full Text | PDF β-Catenin (CTNNB1); interferon regulatory factor 8 (IRF8) doi:10.1038/scibx.2013.1220 In vitro and mouse studies suggest simultaneously increasing IRF8 expression and inhibiting CTNNB1 could help treat CML. Full Text | PDF Histone deacetylase 6 (HDAC6); microRNA-548m (miR-548m); c-Myc (MYC) doi:10.1038/scibx.2013.1221 In vitro and mouse studies suggest inhibiting HDAC6 and MYC could help treat MCL and other NHLs. Full Text | PDF Prostate-specific membrane antigen (PSMA; FOLH1; GCPII); CD3 doi:10.1038/scibx.2013.1222 In vitro and mouse studies suggest PSMA-targeting small molecule–antibody conjugates could help treat prostate cancer. Full Text | PDF Cardiovascular disease Top Myosin heavy chain 7 cardiac muscle-β (MYH7) doi:10.1038/scibx.2013.1223 Mouse studies suggest RNAi that targets a disease-causing mutation in MYH7 could help prevent hypertrophic cardiomyopathy (HCM). Full Text | PDF Gastrointestinal disease Top ST3 β-galactoside α-2,3-sialytransferase 4 (ST3GAL4) doi:10.1038/scibx.2013.1224 Mouse studies suggest removing oligosaccharide sialyl(α2,3)lactose (3SL) from breast milk could help prevent colitis in susceptible infants. Full Text | PDF Infectious disease Top Unknown doi:10.1038/scibx.2013.1225 In vitro and mouse studies identified 5-nitroimidazole (5-NI) derivatives that could help treat drug-resistant bacterial and protozoan infections. Full Text | PDF Transforming growth factor-β (TGFB; TGF-β); integrin αVβ8 doi:10.1038/scibx.2013.1226 Mouse studies suggest inhibiting TGF-β or integrin αVβ8 could help prevent chronic helminth infection. Full Text | PDF DNA gyrase doi:10.1038/scibx.2013.1227 In vitro and mouse studies identified thiazolopyridine urea DNA gyrase inhibitors that could be useful for treating tuberculosis. Full Text | PDF Mycobacterium tuberculosis transmembrane transport protein 3 (mmpL3) doi:10.1038/scibx.2013.1228 In vitro and mouse studies identified indol-2-carboxamides that could help treat tuberculosis. Full Text | PDF Dihydroorotate dehydrogenase (DHODH) doi:10.1038/scibx.2013.1229 Cell culture studies suggest inhibiting pyrimidine synthesis could help prevent or treat RNA viral infections. Full Text | PDF IL-29 (IFNL1) doi:10.1038/scibx.2013.1230 Studies in patient samples suggest IL-29 could help treat the viral infections that frequently accompany atopic dermatitis. Full Text | PDF Inflammation Top IgE doi:10.1038/scibx.2013.1231 In vitro and mouse studies suggest inhibiting weak affinity allergen–IgE interactions could help prevent allergies. Full Text | PDF Neurology Top Eukaryotic translation initiation factor 2α kinase 3 (EIF2AK3; PERK) doi:10.1038/scibx.2013.1232 Mouse studies suggest inhibiting PERK could help treat prion-associated diseases. Full Text | PDF Solute carrier family 12 potassium-chloride transporter member 5 (SLC12A5; KCC2) doi:10.1038/scibx.2013.1233 In vitro and rat studies suggest stimulating chloride extrusion through KCC2 activation could help treat pain. Full Text | PDF Toll-like receptor 4 (TLR4) doi:10.1038/scibx.2013.1234 Rat studies suggest antagonizing TLR4 in the ventrolateral periaqueductal gray (vlPAG) region of the brain could help prevent morphine tolerance. Full Text | PDF Various Top Cold-inducible RNA-binding protein (CIRP) doi:10.1038/scibx.2013.1235 In vitro and rodent studies suggest decreasing CIRP levels could help treat hemorrhagic shock and sepsis. Full Text | PDF Distillery: Techniques Assays and screens Top Metabolite suppression profiling to understand the mechanism of action for antibacterial compounds doi:10.1038/scibx.2013.1236 Metabolite suppression profiles can help define the mechanism of action for antibacterial compounds. Full Text | PDF Computational models Top Bioinformatics-based approach to identify combined microRNA- and mRNA-derived cancer signatures doi:10.1038/scibx.2013.1237 A bioinformatics approach to predict mRNA and miRNA connectivity in transcriptional networks could help identify genetic vulnerabilities in cancer cells. Full Text | PDF Disease models Top Fibrillin 1 (Fbn1)-mutant mouse models of systemic scleroderma doi:10.1038/scibx.2013.1238 Mice harboring mutations in the integrin-binding domain of Fbn1 could help model systemic scleroderma. Full Text | PDF In vitro model to predict pharmacokinetic parameters important to antimalarial drug efficacy doi:10.1038/scibx.2013.1239 An in vitro model to predict pharmacokinetic parameters important for antimalarial drug efficacy could help improve drug dosing. Full Text | PDF Drug delivery Top Cyclodextrin-modified dendritic polyamine (DexAM) construct for delivery of stem cell differentiation factors doi:10.1038/scibx.2013.1240 DexAM constructs that simultaneously deliver small interfering RNA and small molecules could be used to control stem cell differentiation. Full Text | PDF Drug platforms Top Gene-specific transcriptional activation using DNA (cytosine-5-)-methyltransferase 1 (DNMT1)-RNA interactions doi:10.1038/scibx.2013.1241 Suppression of DNMT1-mediated gene methylation using gene-specific RNAs could provide a mechanism for activating gene expression. Full Text | PDF Site-directed mRNA editing to correct genetic diseases doi:10.1038/scibx.2013.1242 A method to site-specifically edit mRNA could be used to correct genetic mutations associated with inherited diseases. Full Text | PDF Markers Top Genomic rearrangements in the androgen receptor (AR) as an androgen-independent prostate cancer resistance mechanism doi:10.1038/scibx.2013.1243 In vitro studies suggest genomic rearrangements in the AR gene driving androgen-independent prostate cancer growth could help predict drug response. Full Text | PDF Top

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