SciBX: Science-Business eXchange Contents: August 1 2013, Volume 6 / Issue 29

TABLE OF CONTENTS August 1 2013, Volume 6 / Issue 29 Analysis Cover Story Targets and Mechanisms Tools The Distillery: Therapeutics Cancer Cardiovascular disease Endocrine/metabolic disease Infectious disease Neurology Various The Distillery: Techniques Assays and screens Computational models Disease models Drug platforms Markers Advertisement Biopharma Dealmakers A supplement to Nature Biotechnology and Nature Reviews Drug Discovery  The May 2013 issue of Biopharma Dealmakers showcases companies with partnering opportunities and contains a special feature on oncology. This week, find out about how you can collaborate with Roche Partnering. 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 Connecting the microbiome to obesity-associated cancers Kai-Jye Lou doi:10.1038/scibx.2013.743 Researchers in Japan have described a pathway that shows how obesity-associated changes in the gut microbiome could lead to liver cancer. The findings lay a foundation for developing new microbiome-targeted diagnostics to identify at-risk individuals and intervention strategies. Full Text | PDF Targets and Mechanisms Top Prostate cancer's nerves Lauren Martz doi:10.1038/scibx.2013.744 A team from the Albert Einstein College of Medicine of Yeshiva University has found that inhibiting autonomic nerve signaling in the prostate with clinically approved drugs could help prevent prostate cancers. Next the researchers will have to determine whether the approach can treat established disease. Full Text | PDF Activating memory Lev Osherovich doi:10.1038/scibx.2013.745 A French and Indian team has proof of concept for activating a brain pathway involved in learning and memory with a peripherally delivered small molecule. The compound activates two histone acetyltransferases that enhance brain activity in wild-type mice, but its utility in neurodegenerative disease remains to be seen. Full Text | PDF Tools Top The liver's new bud Benjamin Boettner doi:10.1038/scibx.2013.746 Japanese researchers have produced vascularized human liver tissue that displays promising metabolic and regenerative capacity in mice. The group now aims to scale up the procedure to generate bigger tissue segments and will test functionality in larger animal models. Full Text | PDF Distillery: Therapeutics Cancer Top Integrin β3 (GPIIIa; CD61) doi:10.1038/scibx.2013.747 Studies in mice suggest antagonizing CD61 could help treat AML. Full Text | PDF Cytosolic branched chain amino-acid transaminase 1 (BCAT1); isocitrate dehydrogenase 1 (IDH1) doi:10.1038/scibx.2013.748 Patient tissue and mouse studies suggest inhibiting BCAT1 could be useful for treating gliomas with wild-type IDH1. Full Text | PDF Histone deacetylase 1 (HDAC1); HDAC6; estrogen receptor-α doi:10.1038/scibx.2013.749 Cell culture studies suggest bifunctional compounds inhibiting HDAC1, HDAC6 and estrogen receptors (ERs) could help treat ER+ breast cancer. Full Text | PDF Tissue factor doi:10.1038/scibx.2013.750 In vitro and mouse studies suggest inhibiting alternatively spliced tissue factor (asTF) could help treat breast cancer. Full Text | PDF Hyaluronan synthase 2 (HAS2); hyaluronidase 2 (HYAL2) doi:10.1038/scibx.2013.751 In vitro and rodent studies suggest extremely high molecular mass hyaluronan (HMM-HA) could help treat cancer. Full Text | PDF Phosducin-like 3 (PDCL3); VEGF receptor 2 (KDR/Flk-1; VEGFR-2) doi:10.1038/scibx.2013.752 Cell culture studies suggest inhibiting PDCL3 could help treat VEGFR-2-dependent angiogenesis in tumors. Full Text | PDF Potassium channel KCa2.3 (KCNN3; SK3); transmembrane protein 142A (ORAI1; TMEM142A; CRACM1) doi:10.1038/scibx.2013.753 Mouse studies suggest inhibiting the interaction between the SK3 and ORAI1 channels could help prevent cancer metastasis. Full Text | PDF Purinergic receptor P2Y G protein–coupled 2 (P2RY2; P2Y2) doi:10.1038/scibx.2013.754 In vitro and mouse studies suggest antagonizing the adenine nucleotide receptor P2Y2 could help prevent cancer metastasis. Full Text | PDF Deoxycholic acid doi:10.1038/scibx.2013.755 Mouse studies suggest decreasing deoxycholic acid production or deoxycholic acid–producing bacteria in the gut could help prevent obesity-associated hepatocellular carcinoma (HCC). Full Text | PDF Histone deacetylase 10 (HDAC10) doi:10.1038/scibx.2013.756 Computational and cell culture studies suggest HDAC10 inhibitors could enhance chemotherapy in treating neuroblastoma. Full Text | PDF Kallikrein-related peptidase 4 (KLK4) doi:10.1038/scibx.2013.757 Cell culture and mouse studies suggest inhibition of KLK4 could help treat prostate cancer. Full Text | PDF Cardiovascular disease Top Not applicable doi:10.1038/scibx.2013.758 A zebrafish study suggests atrial cardiomyocytes can be converted to ventricular cardiomyocytes, which could be useful for treating heart failure. Full Text | PDF Endocrine/metabolic disease Top N-sulfoglucosamine sulfohydrolase (SGSH; HNS) doi:10.1038/scibx.2013.759 Animal studies suggest SGSH gene therapy could help treat mucopolysaccharidosis IIIA (MPS IIIA). Full Text | PDF Infectious disease Top Not applicable doi:10.1038/scibx.2013.760 In vitro and mouse studies suggest m-terphenyl and dipyridylbenzene compounds could help treat protozoan infections. Full Text | PDF Capsular polysaccharide export protein (wza) doi:10.1038/scibx.2013.761 Cell culture studies identified a glycomimetic inhibitor of wza that could help treat Gram-negative bacterial infections. Full Text | PDF Not applicable doi:10.1038/scibx.2013.762 A chemically inactivated, whole-parasite vaccine could help treat malaria infection. Full Text | PDF Plasmodium falciparum multidrug resistance protein 1 (PfMDR1) doi:10.1038/scibx.2013.763 In vitro and cell culture studies identified a PfMDR1-targeting compound, ACT-213615, that could help treat malaria. Full Text | PDF Mycobacterium tuberculosis long-chain fatty acid–CoA ligase (fadD32) doi:10.1038/scibx.2013.764 In vitro and mouse studies identified fadD32 inhibitors that could help treat tuberculosis. Full Text | PDF Neurology Top μ-Opioid receptor (OPRM1; MOR); metabotropic glutamate receptor subtype 5 (mGluR5; GRM5) doi:10.1038/scibx.2013.765 A mouse study suggests bivalent ligands with OPRM1 agonist and mGluR5 antagonist activity could help treat chronic inflammatory pain. Full Text | PDF Various Top CD36 (GPIV) doi:10.1038/scibx.2013.766 In vitro and mouse studies suggest inhibiting CD36 could help suppress inflammation in atherosclerosis, AD and type 2 diabetes. Full Text | PDF Ribosome doi:10.1038/scibx.2013.767 In vitro studies have questioned the mechanism of action for ataluren (PTC124), which is in clinical development to treat CF and Duchenne muscular dystrophy (DMD). Full Text | PDF Distillery: Techniques Assays and screens Top Quantification of clustered, regularly interspaced short palindromic repeats (CRISPR)-based editing system specificity doi:10.1038/scibx.2013.768 Quantification of off-target mutagenesis in CRISPR-based genome editing systems could help evaluate CRISPR systems for potential therapeutic applications and guide the development of CRISPR systems with increased accuracy. Full Text | PDF Computational models Top Computational model for predicting P glycoprotein (MDR1; ABCB1; P-gp; CD243) substrates doi:10.1038/scibx.2013.769 A computational model to predict whether a compound may be exported by P-gp could help identify cancer therapeutics that avoid P-gp-mediated resistance. Full Text | PDF Disease models Top Mouse model for prostate cancer driven by v-ets erythroblastosis virus E26 oncogene homolog (ERG) translocations doi:10.1038/scibx.2013.770 Mice with prostate-specific Erg expression could be used as a model to study prostate cancer pathogenesis. Full Text | PDF Mouse models for choroidal neovascularization (CNV) and age-related macular degeneration (AMD) doi:10.1038/scibx.2013.771 Mouse models for CNV could help identify therapeutics to treat AMD. Full Text | PDF Drug platforms Top Human bone marrow–specific extracellular matrix (ECM) substrates doi:10.1038/scibx.2013.772 Human bone marrow–specific ECM substrates could be used to culture stem cells for therapeutic applications. Full Text | PDF Monoacyl lipopeptide agonist of toll-like receptor 2 (TLR2) as a vaccine adjuvant doi:10.1038/scibx.2013.773 A lipopeptide agonist of TLR2 could boost the efficacy of vaccines against infectious diseases. Full Text | PDF Platform for maturation of human pluripotent stem cell–derived cardiomyocytes doi:10.1038/scibx.2013.774 A platform for generating mature cardiomyocytes from human pluripotent stem cells could aid the development of improved models of cardiovascular disease. Full Text | PDF Self-assembling, osteogenic, polymer-based coating to prevent joint implant failure doi:10.1038/scibx.2013.775 Rodent studies suggest a self-assembling, osteogenic, polymer-based coating could help prevent joint implant failure. Full Text | PDF Markers Top Androgen receptor mutations that convey resistance to second-generation anti–androgen receptor compounds doi:10.1038/scibx.2013.776 Studies in cell culture and in patient samples identified drug resistance mutations that could help guide prostate cancer treatment. Full Text | PDF Galectin-1 (LGALS1) as a prognostic marker of early onset pre-eclampsia doi:10.1038/scibx.2013.777 Monitoring levels of serum LGALS1 could help predict risk of severe pre-eclampsia. Full Text | PDF Top

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