SciBX: Science-Business eXchange Contents: December 12 2013, Volume 6 / Issue 47

TABLE OF CONTENTS December 12 2013, Volume 6 / Issue 47 Analysis Cover Story Targets and Mechanisms Tools The Distillery: Therapeutics Cancer Cardiovascular disease Endocrine/metabolic disease Hematology Infectious disease Neurology Various The Distillery: Techniques Assays and screens Computational models Disease models Drug delivery Drug platforms Imaging Instrumentation Advertisement BioPharma Dealmakers A supplement to Nature Biotechnology and Nature Reviews Drug Discovery The November 2013 issue of BioPharma Dealmakers showcases companies with partnering opportunities. This week, find out about how you can collaborate with Pharnext and Harbour Antibodies 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 T cells go universal Tracey Baas doi:10.1038/scibx.2013.1337 Scientists have engineered T cells that engage in antibody-dependent cellular cytotoxicity and enhance the antitumor potential of any immunotherapeutic antibody. The team plans to test the T cell and antibody combination in clinical trials in which antibody monotherapy did not yield remissions. Full Text | PDF Targets and Mechanisms Top ClpPing persistence Chris Cain doi:10.1038/scibx.2013.1338 Northeastern University researchers have combined traditional antibiotics with compounds that activate bacterial clpP protease and cured mice with severe, highly drug-resistant Staphylococcus biofilm infections. Arietis is developing analogs of the compounds to treat persistent bacterial infections. Full Text | PDF Tools Top Plan B for anti-miRNA Lev Osherovich doi:10.1038/scibx.2013.1339 How to formulate and deliver therapeutic anti-microRNAs has been a big challenge in the burgeoning anti-miRNA space. Now, a San Diego team has proof of concept for a surprisingly simple way to deliver these molecules into the blood stream using engineered B cells. Full Text | PDF Family seeds Amy Donner doi:10.1038/scibx.2013.1340 In attempting to make specific microRNA inhibitors, companies have assumed that anti-miRNAs should approximate the length of the miRNA target. Now, an international team has generated in vivo proof of concept that targeting a stretch of only eight nucleotides conserved within an miRNA family can safely and selectively block multiple miRNAs. Full Text | PDF Distillery: Therapeutics Cancer Top Enhancer of zeste homolog 2 (EZH2) doi:10.1038/scibx.2013.1341 Cell culture studies identified a small molecule inhibitor of EZH2 that could help treat EZH2-dependent cancers. Full Text | PDF Histone deacetylase (HDAC); interferon-γ (IFNG; IFN-γ) doi:10.1038/scibx.2013.1342 Mouse studies suggest combining HDAC inhibitors with IFN-γ stimulation may enhance antitumor efficacy. Full Text | PDF B cell lymphoma 2 (BCL-2; BCL2); Bcl-xL; mammalian target of rapamycin complex 1 (mTORC1); mTORC2 doi:10.1038/scibx.2013.1343 Cell culture and mouse studies suggest antagonizing mTORC1 or mTORC2 in combination with BCL-2 and Bcl-xL could be useful for treating K-Ras (KRAS)- or BRAF-mutant CRC. Full Text | PDF Unknown doi:10.1038/scibx.2013.1344 Mouse studies suggest Revlimid lenalidomide helps treat MCL by inhibiting lymphangiogenesis. Full Text | PDF Lysine-specific demethylase 2A (KDM2A; JHDM1A) doi:10.1038/scibx.2013.1345 Patient sample, cell culture and mouse studies suggest decreasing levels of KDM2A could help treat NSCLC. Full Text | PDF IL-6; signal transducer and activator of transcription 3 (STAT3) doi:10.1038/scibx.2013.1346 In vitro and mouse studies suggest inhibiting IL-6 or STAT3 could help treat castration-resistant prostate cancer. Full Text | PDF BRAF; c-jun N-terminal kinase (JNK) doi:10.1038/scibx.2013.1347 In vitro and mouse studies suggest the BRAF inhibitor Zelboraf vemurafenib could induce cutaneous squamous cell carcinoma (cSCC) by inhibiting JNK signaling. Full Text | PDF Cardiovascular disease Top Purinergic receptor P2Y G protein–coupled 1 (P2RY1; P2Y1) doi:10.1038/scibx.2013.1348 In vitro and rat studies have identified P2Y1 antagonists that could help treat thrombosis. Full Text | PDF MicroRNA-33a (miR-33a); miR-33b doi:10.1038/scibx.2013.1349 Mouse and primate studies suggest an 8mer anti-miRNA that targets both miR-33a and miR-33b could help treat cardiovascular disease. Full Text | PDF Protein tyrosine phosphatase non-receptor type 5 (PTPN5; STEP); p38 mitogen-activated protein kinase (p38 MAPK; MAPK14) doi:10.1038/scibx.2013.1350 Rat studies identified a degradation-resistant STEP peptide that could help treat ischemia/reperfusion injury. Full Text | PDF Endocrine/metabolic disease Top Nicotinic acid adenine dinucleotide phosphate (NAADP) doi:10.1038/scibx.2013.1351 Cell culture and mouse studies suggest NAADP analogs could help treat type 2 diabetes. Full Text | PDF Serotonin (5-HT2C) receptor doi:10.1038/scibx.2013.1352 Mouse studies suggest agonizing the 5-HT2C receptor on proopiomelanocortin (POMC) neurons could help treat diabetes. Full Text | PDF Hematology Top Retinoic acid receptor (RAR) doi:10.1038/scibx.2013.1353 Mouse studies suggest RAR antagonists could help treat myelofibrosis. Full Text | PDF Infectious disease Top Bacterial RNA polymerase doi:10.1038/scibx.2013.1354 Computational and SAR studies suggest anthranilic acid compounds could be useful for treating Gram-positive bacterial infections. Full Text | PDF CD36 (GPIV) doi:10.1038/scibx.2013.1355 In vitro studies suggest anti-CD36 antibodies could help treat HIV. Full Text | PDF Ataxia telangienctasia mutated (ATM); DNA damage response doi:10.1038/scibx.2013.1356 Mouse studies suggest anthracyclines could be used to treat sepsis by activating the DNA damage response. Full Text | PDF clpP doi:10.1038/scibx.2013.1357 Cell culture and mouse studies suggest combining the antibiotic acyldepsipeptide 4 (ADEP4) with rifampicin could help eradicate biofilms. Full Text | PDF Neurology Top Thyroid hormone receptor-α doi:10.1038/scibx.2013.1358 Studies in human tissue and rabbits suggest thyroid hormone receptor-α agonists could protect against neurodevelopmental damage caused by intraventricular hemorrhage in preterm infants. Full Text | PDF Various Top Not applicable doi:10.1038/scibx.2013.1359 In vitro and rat studies suggest a 2,4-dinitrophenol analog could help treat nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes. Full Text | PDF Distillery: Techniques Assays and screens Top Multistage volumetric bar chart chip (MV-Chip) to detect DNA sequences doi:10.1038/scibx.2013.1360 A volumetric bar chart chip could be used to detect and quantify DNA for diagnostic purposes. Full Text | PDF Computational models Top Genome-based classification of lung tumors and treatments improves patient survival doi:10.1038/scibx.2013.1361 Genome-based classification of lung cancer could help improve patient survival. Full Text | PDF Disease models Top Induced pluripotent stem (iPS) cell model of Phelan-McDermid syndrome (PMDS) doi:10.1038/scibx.2013.1362 Studies in cell culture suggest patient-derived iPS cells could be useful for studying PMDS. Full Text | PDF Mouse model of familial dysautonomia (FD) with neural crest lineage–specific knockout of inhibitor of κ-light polypeptide gene enhancer in B-cells kinase complex-associated protein (Ikbkap) doi:10.1038/scibx.2013.1363 A mouse model of FD with conditional knockout of Ikbkap in neural crest cells could help identify new therapeutics to treat the disease. Full Text | PDF SH3 and multiple ankyrin repeat domains 3 (Shank3; Prosap2; Spank-2)-overexpressing mice as a model of hyperkinetic neuropsychiatric disorders doi:10.1038/scibx.2013.1364 Mice overexpressing Shank3 could provide a model of hyperkinetic neuropsychiatric disorders such as mania. Full Text | PDF Drug delivery Top Short RNA delivery by engineered B cells doi:10.1038/scibx.2013.1365 A study in cell culture and mice suggests engineered B cells could be used to deliver therapeutic short RNAs to other immune cells. Full Text | PDF Staggered lamellae nanostructures for drug delivery doi:10.1038/scibx.2013.1366 Staggered lamellae polyprodrug nanostructures could be useful for drug delivery. Full Text | PDF Drug platforms Top Chimeric Fc γ-receptor III (CD16; FCGR3)-expressing T cells to improve antibody-dependent cell cytotoxicity (ADCC) doi:10.1038/scibx.2013.1367 Mouse studies suggest T cells expressing a chimeric receptor that binds to antibody Fc regions could be used to treat various cancers when combined with antibody therapies. Full Text | PDF Transcription activator–like effector nucleases (TALENs) selectively targeting individual microRNAs doi:10.1038/scibx.2013.1368 A library of TALEN-mediated miRNA knockouts could help study miRNA function. Full Text | PDF Imaging Top Metabotropic glutamate receptor subtype 1 (mGluR1; GRM1) binding PET radioligand for in vivo imaging doi:10.1038/scibx.2013.1369 A PET radioligand that binds mGluR1 could help diagnose and study neuropsychiatric disorders. Full Text | PDF Instrumentation Top Microwell displacement amplification system (MIDAS), a parallel polymerase cloning system for single-cell genome sequencing doi:10.1038/scibx.2013.1370 MIDAS enables massively parallel polymerase cloning, which decreases bias and improves efficiency in single-cell genome sequencing. Full Text | PDF Top

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