SciBX: Science-Business eXchange Contents: November 21 2013, Volume 6 / Issue 45

TABLE OF CONTENTS November 21 2013, Volume 6 / Issue 45 Analysis Cover Story Targets and Mechanisms Tools The Distillery: Therapeutics Autoimmune disease Cancer Cardiovascular disease Dental disease Endocrine/metabolic disease Infectious disease Inflammation Musculoskeletal disease Neurology Various The Distillery: Techniques Computational models Disease models Drug platforms Imaging Advertisement Biopharma Dealmakers A supplement to Nature Biotechnology and Nature Reviews Drug Discovery Check out the latest issue of Biopharma Dealmakers, which includes the following features: - Pharma looks to neurotech to fill the void - Taking notice of epigenetic deals - Biopharma Dealmakers antibody update  Click here to read the issue for FREE! 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 Glucokinase alternative Chris Cain doi:10.1038/scibx.2013.1279 Compounds that directly activate glucokinase effectively reduce blood sugar in patients with diabetes but increase the risk of adverse hypoglycemic events. Now, researchers from Amgen have identified compounds that act via a glucokinase regulator, opening the door to a potentially safer strategy to modulate hepatic glucokinase activity. Full Text | PDF Targets and Mechanisms Top Riding the integrin wave in thrombosis Benjamin Boettner doi:10.1038/scibx.2013.1280 The use of platelet integrin α2bβ3 inhibitors in thrombosis, although clinically effective, has been limited by an associated high risk of bleeding. Now, researchers at the University of Illinois at Chicago have developed an integrin α2bβ3 inhibitor that suppresses arterial thrombosis without triggering bleeding in mice. Full Text | PDF Getting to the root of periodontitis Michael J. Haas doi:10.1038/scibx.2013.1281 Current therapies do not target the underlying immune response that drives periodontitis. Looking to change that, a team from the U.S. and Brazil has shown that microparticles loaded with CCL22 recruited Treg cells to the gingiva and slowed periodontitis progression in mice and dogs. Full Text | PDF Tools Top Naïve human iPS cells Lauren Martz doi:10.1038/scibx.2013.1282 The inability to generate fully undifferentiated human iPS cells in vitro may contribute to inefficient and inconsistent differentiation of the cells. An Israeli team thinks a small molecule and cytokine cocktail capable of maintaining human cells in a more fully undifferentiated state could solve the problem. Full Text | PDF Distillery: Therapeutics Autoimmune disease Top Bromodomain containing 2 (BRD2); BRD4 doi:10.1038/scibx.2013.1283 Cell culture and mouse studies suggest inhibiting the BET bromodomains of BRD2 and BRD4 could be useful for treating autoimmune disease. Full Text | PDF Cancer Top Glutamate-cysteine ligase catalytic subunit (GCLC); glutathione peroxidase 1 (GPX1) doi:10.1038/scibx.2013.1284 In vitro studies suggest inhibiting glutathione metabolism could help treat AML. Full Text | PDF HER2 (EGFR2; ErbB2; neu); PD-1 receptor (PDCD1; PD-1; CD279) doi:10.1038/scibx.2013.1285 Mouse studies suggest inhibiting PD-1 could enhance the antitumor effects of HER2 chimeric antigen receptor (CAR) T cell therapies. Full Text | PDF Uridine phosphorylase 1 (UPP1) doi:10.1038/scibx.2013.1286 Cell culture studies identified UPP1 inhibitors that could be useful for improving the efficacy of 5-fluorouracil (5-FU) chemotherapy. Full Text | PDF Neurotrophic tyrosine kinase receptor 1 (NTRK1; TrkA) doi:10.1038/scibx.2013.1287 In vitro and mouse studies suggest TrkA inhibitors could help treat a subgroup of patients with lung cancer. Full Text | PDF Receptor tyrosine kinase–like orphan receptor 1 (ROR1); ROR2 doi:10.1038/scibx.2013.1288 In vitro and mouse studies suggest inhibiting ROR2 could help treat invasive melanoma. Full Text | PDF Cardiovascular disease Top Integrin β3 (GPIIIa; CD61); guanine nucleotide binding protein (G protein) α13 (GNA13) doi:10.1038/scibx.2013.1289 Mouse studies suggest selectively inhibiting CD61 interactions with GNA13 could help prevent thrombosis with fewer bleeding side effects than marketed CD61 antagonists. Full Text | PDF Dental disease Top Chemokine CC motif ligand 22 (CCL22) doi:10.1038/scibx.2013.1290 Animal studies suggest CCL22-loaded microparticles could help treat periodontitis. Full Text | PDF Endocrine/metabolic disease Top Glucokinase (GCK; GK); glucokinase regulator (GCKR; GKRP) doi:10.1038/scibx.2013.1291 In vitro and mouse studies identified compounds that could help treat type 2 diabetes by binding GKRP and disrupting its interaction with GK. Full Text | PDF Proteasome; uroporphyrinogen III synthase (UROS) doi:10.1038/scibx.2013.1292 Mouse and cell culture studies suggest proteasome inhibitors could be useful for treating congenital erythropoietic porphyria, which is caused by destabilizing mutations in UROS. Full Text | PDF Infectious disease Top Ebola glycoprotein GP1; Ebola glycoprotein GP2 doi:10.1038/scibx.2013.1293 Primate studies suggest combining anti-Ebola antibodies plus interferon-α (IFNA; IFN-α) could help treat Ebola virus. Full Text | PDF IL-12; natural killer p30 receptor (NKp30; NCR3; CD337) doi:10.1038/scibx.2013.1294 Patient and cell culture studies suggest IL-12 can increase NKp30 expression and enhance anticryptococcal immunity. Full Text | PDF Plasmodium falciparum phosphoethanolamine N-methyltransferase (PfPMT) doi:10.1038/scibx.2013.1295 Cell culture studies suggest inhibiting PfPMT could help prevent P. falciparum infection and transmission. Full Text | PDF Inflammation Top p38 mitogen-activated protein kinase (p38 MAPK; MAPK14); tumor necrosis factor-α (TNF-α) doi:10.1038/scibx.2013.1296 In vitro studies identified dibenzoxepinone-based p38 MAPK inhibitors that could help treat inflammatory diseases. Full Text | PDF Musculoskeletal disease Top NADPH oxidase 4 (NOX4) doi:10.1038/scibx.2013.1297 Studies in mice and in human samples suggest inhibiting NOX4 could help treat osteoporosis. Full Text | PDF Neurology Top Chromosome 9 open reading frame 72 (C9orf72) doi:10.1038/scibx.2013.1298 Studies in patient samples and mice suggest antisense oligonucleotides targeting the hexanucleotide repeat in C9orf72 could help treat some patients with ALS. Full Text | PDF Enhancer of zeste homolog 2 (EZH2) doi:10.1038/scibx.2013.1299 In vitro and mouse studies suggest inhibiting EZH2 could help treat ataxia telangiectasia. Full Text | PDF Not applicable doi:10.1038/scibx.2013.1300 Rat studies suggest deep brain stimulation could be useful for promoting recovery of motor function following SCI. Full Text | PDF Various Top DNA; topoisomerase II (TOP2) doi:10.1038/scibx.2013.1301 In vitro studies identified analogs of the natural product chartreusin that could serve as lead compounds to help treat cancer or mycobacterial infection. Full Text | PDF Distillery: Techniques Computational models Top Analysis of adverse events database to identify mechanisms underlying side effects doi:10.1038/scibx.2013.1302 In silico and mouse studies suggest analysis of adverse events database can identify new targets that separate beneficial therapeutic effects from adverse events. Full Text | PDF Disease models Top Mouse model of hemolytic anemia induced by malaria drugs doi:10.1038/scibx.2013.1303 A mouse model of hemolytic anemia could be useful for evaluating the tolerability of antimalarial compounds. Full Text | PDF Drug platforms Top A vaccine based on a stabilized variant of respiratory syncytial virus (RSV) F protein doi:10.1038/scibx.2013.1304 A stabilized variant of RSV F protein could be used as a vaccine antigen to prevent RSV infection. Full Text | PDF Naïve human stem cell medium for maintenance of human induced pluripotent stem (iPS) cells in a naïve state doi:10.1038/scibx.2013.1305 In vitro studies identified culture conditions to maintain human iPS cells in a naïve state. Full Text | PDF Small molecule target discovery using forward genetics doi:10.1038/scibx.2013.1306 In vitro, cell culture and mouse studies suggest a high throughput small hairpin RNA screening platform could be useful for identifying the targets of lead compounds. Full Text | PDF Imaging Top Optical metabolic imaging for diagnosing cancer and assessing treatment response doi:10.1038/scibx.2013.1307 Optical metabolic imaging could help diagnose cancers and assess response to treatment. Full Text | PDF Top

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