SciBX: Science-Business eXchange Contents: April 17 2014, Volume 7 / Issue 15

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TABLE OF CONTENTS April 17 2014, Volume 7 / Issue 15 Analysis Cover Story Translational Notes Targets and Mechanisms The Distillery: Therapeutics Cancer Cardiovascular disease Dental disease Inflammation Neurology Various The Distillery: Techniques Assays and screens Chemistry Drug platforms Markers Advertisement Biopharma Dealmakers A supplement to Nature Biotechnology and Nature Reviews Drug Discovery The March 2014 issue of Biopharma Dealmakers showcases companies with partnering opportunities. This week, find out about how you can collaborate with Amunix Operating Inc.   Analysis Cover Story Top Contaminating cancer genomes Chris Cain doi:10.1038/scibx.2014.418 Two European teams have pinpointed a DNA-protective enzyme as a chemically tractable target whose inhibition kills cancer cells by accelerating DNA damage. Both groups have identified small molecule inhibitors of the enzyme and are looking to partner with industry. Full Text | PDF Translational Notes Top Translational tidbits Kai-Jye Lou doi:10.1038/scibx.2014.419 AstraZeneca had a busy March, announcing five new public-private partnerships and launching its Open Innovation website to list additional partnership opportunities. Full Text | PDF Expanding into new (bromo)domains Michael J. Haas doi:10.1038/scibx.2014.420 The Neomed Institute has begun development of its first cancer therapeutic, a BRD4 inhibitor from Epigenetix that the not-for-profit organization thinks could have a selectivity advantage over competing molecules. Full Text | PDF Targets and Mechanisms Top Unfolding triple-negative breast cancer Benjamin Boettner doi:10.1038/scibx.2014.421 A team from Weill Cornell Medical College has found a unifying feature of triple-negative breast cancers—overactivation of the transcription factor X-box binding protein 1. Blocking expression of the target decreases tumor formation and relapse in mice, but more druggable targets upstream of it might be better suited for further development. Full Text | PDF Distillery: Therapeutics Cancer Top Casein kinase 1α (CSNK1A; CKI-α) doi:10.1038/scibx.2014.422 Mouse and cell culture studies suggest inhibiting CKI-α could help treat AML. Full Text | PDF DNA (cytosine-5-)-methyltransferase 3α (DNMT3A) R882H doi:10.1038/scibx.2014.423 In vitro studies suggest targeting DNMT3A R882H could be useful for treating AML. Full Text | PDF Fas receptor (CD95) doi:10.1038/scibx.2014.424 In vitro and mouse studies suggest blocking CD95 signaling could help treat breast cancer. Full Text | PDF miR-BART9 doi:10.1038/scibx.2014.425 In vitro and mouse studies suggest blocking Epstein-Barr virus (EBV) miR-BART9 could help treat EBV-associated cancers. Full Text | PDF Signal transducer and activator of transcription 3 (STAT3) doi:10.1038/scibx.2014.426 In vitro and mouse studies identified a STAT3-specific binding peptide that could help treat cancer. Full Text | PDF Tubulin doi:10.1038/scibx.2014.427 In vitro and human studies suggest paclitaxel induces cell death by promoting the formation of abnormal multipolar spindles that lead to chromosomal missegregation during mitosis. Full Text | PDF PC4 and SFRS1-interacting protein (PSIP1; LEDGF; p75; LEDGF/p75) doi:10.1038/scibx.2014.428 Studies in cell culture and patient samples suggest inhibiting LEDGF expression could help treat HPV+ cervical cancers. Full Text | PDF Ras-related associated with diabetes (RRAD) doi:10.1038/scibx.2014.429 Human sample, cell culture and mouse studies suggest increasing RRAD activity could help treat ovarian cancer. Full Text | PDF Cardiovascular disease Top Transmembrane 6 superfamily member 2 (TM6SF2) doi:10.1038/scibx.2014.430 Studies in human samples and mice suggest inhibiting TM6SF2 could help lower total cholesterol levels. Full Text | PDF Dental disease Top IL-17A; IL-23 doi:10.1038/scibx.2014.431 Patient and mouse studies suggest inhibiting IL-17A or IL-23 could help treat the severe periodontitis that develops in patients who have leukocyte adhesion deficiency type I (LAD I). Full Text | PDF Inflammation Top Potassium channel Kv1.3 (KCNA3) doi:10.1038/scibx.2014.432 Rat studies suggest KCNA3 antagonists could be useful for treating asthma. Full Text | PDF Neurology Top RE1-silencing transcription factor (REST; NRSF) doi:10.1038/scibx.2014.433 Studies in human samples and mice suggest activating REST could help protect against age-related neurodegeneration. Full Text | PDF Microtubule-associated protein-τ (MAPT; tau; FTDP-17) doi:10.1038/scibx.2014.434 Mouse studies suggest inhibiting the oligomeric extracellular form of tau could help treat tauopathies associated with AD and FTD. Full Text | PDF Various Top Platelet/endothelial cell adhesion molecule 1 (PECAM1; CD31) doi:10.1038/scibx.2014.435 In vitro and mouse studies suggest increasing CD31 signaling could help treat inflammatory and autoimmune diseases. Full Text | PDF Tumor necrosis factor-α (TNF-α) doi:10.1038/scibx.2014.436 Mouse and in vitro culture studies identified a small molecule TNF-α inhibitor that could be useful for treating autoimmune and inflammatory diseases. Full Text | PDF IL-21 doi:10.1038/scibx.2014.437 Mouse studies suggest inhibiting IL-21 signaling could help prevent ischemia/reperfusion injury in stroke. Full Text | PDF Distillery: Techniques Assays and screens Top A refined, allele-specific quantitative PCR assay called Intplex for analysis of circulating cell-free DNA (cfDNA) mutations doi:10.1038/scibx.2014.438 Intplex could be used to characterize small, highly fragmented, tumor-derived cfDNA for diagnostic applications. Full Text | PDF Tumor endothelial marker (TEM)-expressing circulating endothelial cells (CECs) as a blood-based marker to detect tumors and monitor response to antiangiogenic therapy doi:10.1038/scibx.2014.439 Studies in human samples and mice suggest TEM+ CECs could help detect the presence of tumors and monitor tumor response to antiangiogenic therapy. Full Text | PDF Chemistry Top Isoacyl dipeptides to increase insulin yield from chemical synthesis doi:10.1038/scibx.2014.440 Chemical synthesis of insulin using isoacyl dipeptides could improve yield of the hormone. Full Text | PDF Drug platforms Top Binary nylon-3 copolymers containing cationic and hydrophobic subunits for antimicrobial activity doi:10.1038/scibx.2014.441 In vitro studies identified binary nylon-3 copolymers containing cationic and hydrophobic subunits that could help treat and prevent bacterial infections. Full Text | PDF Clustered, regularly interspaced short palindromic repeats (CRISPR)-based genome editing platform to treat genetic liver disease doi:10.1038/scibx.2014.442 Mouse studies suggest CRISPR-based genome editing could be used to treat tyrosinemia type I (TTI), a fatal disease resulting from mutation of fumarylacetoacetate hydrolase (FAH) and accumulation of toxic metabolites. Full Text | PDF Mice with directed integration of human immunoglobulin transgenes to produce chimeric antibodies with fully human variable domains doi:10.1038/scibx.2014.443 Transgenic mice that produce chimeric antibodies with human variable domains could be used for therapeutic antibody discovery. Full Text | PDF Markers Top Markers of distinct sonic hedgehog homolog (SHH)-driven medulloblastomas doi:10.1038/scibx.2014.444 Mouse and sequencing studies suggest SHH-driven medulloblastomas in adults, children and infants are molecularly distinct from one another and should be treated using different protocols. Full Text | PDF MicroRNA-155 (miR-155) as a predictive marker of breast cancer response to radiation therapy doi:10.1038/scibx.2014.445 In vitro and mouse studies suggest miR-155 levels could help predict breast cancer response to radiation therapy. Full Text | PDF Mitochondrial DNA (mtDNA) mutations and impaired glucose utilization as markers of sensitivity to biguanides in cancer doi:10.1038/scibx.2014.446 Cell culture studies suggest mutations in mtDNA and impaired glucose utilization could be useful as markers to help predict cancer sensitivity to biguanides, which inhibit oxidative phosphorylation. Full Text | PDF Top

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