SciBX: Science-Business eXchange Contents: April 3 2014, Volume 7 / Issue 13

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TABLE OF CONTENTS April 3 2014, Volume 7 / Issue 13 Analysis Cover Story Translational Notes Targets and Mechanisms Tools The Distillery: Therapeutics Cancer Cardiovascular disease Endocrine/metabolic disease Infectious disease Musculoskeletal disease Neurology The Distillery: Techniques Disease models Drug delivery Drug platforms Imaging Markers 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 PolyTherics   Analysis Cover Story Top Critical mass in diabetes Lauren Martz doi:10.1038/scibx.2014.360 A University of Bremen group has found a new target—STK4—that can increase β cell mass and may provide an alternative to invasive islet cell transplants to treat diabetes. The team will need to rule out long-term safety issues associated with blocking the kinase. Full Text | PDF Translational Notes Top Bridging the German gap Chris Cain doi:10.1038/scibx.2014.361 Evotec has purchased Bionamics to gain access to a collection of autoimmune assets sourced from German universities. The move is the latest in a series of steps taken by Evotec to complement its fee-for-service operations. Full Text | PDF Targets and Mechanisms Top Narrowing down graft stenosis Benjamin Boettner doi:10.1038/scibx.2014.362 One serious complication after coronary artery bypass graft surgery is hyperplastic growth of the transplant. Now, a U.S. team has reported that this hyperplasia is rooted in the endothelial cells lining the transplanted veins and has shown that blocking TGFβ activity in mice prevents the cellular changes. Full Text | PDF Tools Top Complementing mAbs Kai-Jye Lou doi:10.1038/scibx.2014.363 Genmab and Utrecht University researchers have shown that hexameric IgG complexes can activate the complement cascade. Genmab is now selecting key mutations and antibody candidates to generate IgG antibodies that potently induce complement-dependent cytotoxicity in cancer and infectious disease. Full Text | PDF Distillery: Therapeutics Cancer Top Deoxycytidine kinase (DCK) doi:10.1038/scibx.2014.364 In vitro and mouse studies suggest simultaneously inhibiting two deoxycytidine triphosphate (dCTP) synthesis pathways could help treat ALL. Full Text | PDF Retinoic acid receptor-α (RARA); promyelocytic leukemia (PML); histone deacetylase (HDAC) doi:10.1038/scibx.2014.365 Cell culture studies suggest hybrid retinoic acid–HDAC inhibitors could be useful for treating APL. Full Text | PDF Mitogen-activated protein kinase kinase 4 (MAP2K4; MKK4) doi:10.1038/scibx.2014.366 Cell culture and mouse studies suggest small molecules that induce vacuolization could be used to treat glioblastoma multiforme (GBM). Full Text | PDF G protein–coupled receptor 161 (GPR161) doi:10.1038/scibx.2014.367 Patient sample and cell culture studies suggest targeting GPR161 could be useful for treating triple-negative breast cancer (TNBC). Full Text | PDF Cannabinoid CB2 receptor (CNR2) doi:10.1038/scibx.2014.368 In vitro and mouse studies suggest a CNR2-specific ligand–based photosensitizer could be useful for photodynamic cancer therapy. Full Text | PDF Heat shock protein 90 (Hsp90) doi:10.1038/scibx.2014.369 In vitro and mouse studies suggest a new family of triazole-based Hsp90 inhibitors could help treat cancer. Full Text | PDF IL-23; CD40 doi:10.1038/scibx.2014.370 Mouse studies suggest combination therapy with IL-23 and CD40 mAbs could be more effective at treating cancer than monotherapy. Full Text | PDF CTLA-4 (CD152) doi:10.1038/scibx.2014.371 Mouse studies suggest combining oncolytic Newcastle disease virus (NDV) and CTLA-4 inhibitors could help treat melanoma and other solid tumor types. Full Text | PDF Ubiquitin specific peptidase 9 X-linked (USP9X; FAF); v-ets erythroblastosis virus E26 oncogene homolog (ERG) doi:10.1038/scibx.2014.372 In vitro, human tissue and mouse studies suggest inhibiting USP9X could help treat prostate cancer. Full Text | PDF Cardiovascular disease Top Transforming growth factor-β1 (TGFB1) doi:10.1038/scibx.2014.373 Mouse studies suggest local inhibition of TGFB1 signaling could help prevent stenosis of grafted veins after CABG surgery. Full Text | PDF Endocrine/metabolic disease Top Serine/threonine kinase 4 (STK4) doi:10.1038/scibx.2014.374 In vitro and mouse studies suggest inhibiting STK4 could help treat diabetes. Full Text | PDF Not applicable doi:10.1038/scibx.2014.375 In vitro studies suggest 2-hydroxypropyl-β-cyclodextrin (HPβCD) could help treat lysosomal storage disorders. Full Text | PDF Infectious disease Top HIV integrase doi:10.1038/scibx.2014.376 Macaque studies suggest postcoital dosing of gel-formulated HIV integrase inhibitors could prevent HIV infection. Full Text | PDF Musculoskeletal disease Top Calcium release–activated calcium channel (CRAC); stromal interaction molecule 1 (STIM1); transmembrane protein 142A (ORAI1; TMEM142A; CRACM1) doi:10.1038/scibx.2014.377 In vitro and genetic studies suggest decreasing calcium influx through CRAC could help treat Stormorken syndrome and related diseases. Full Text | PDF Neurology Top Fragile X mental retardation 1 (FMR1) doi:10.1038/scibx.2014.378 In vitro studies suggest inhibiting the binding of CGG repeat–containing FMR1 transcripts to the FMR1 promoter could help treat fragile X syndrome. Full Text | PDF CC chemokine receptor 2 (CCR2; CD192); monocyte chemoattractant protein-1 (MCP-1; CCL2) doi:10.1038/scibx.2014.379 Studies in patient samples and mice suggest depleting CCR2+ inflammatory monocytes could help treat intracerebral hemorrhage. Full Text | PDF Phosphoinositide 3-kinase-δ (PI3Kδ) doi:10.1038/scibx.2014.380 In vitro and mouse studies suggest inhibiting PI3Kδ could help treat stroke. Full Text | PDF Distillery: Techniques Disease models Top Bioluminescent mouse model of HPV+ oral tumors to track the effect of therapeutics doi:10.1038/scibx.2014.381 A bioluminescent mouse model of HPV+ oral tumors could help evaluate potential therapeutic candidates. Full Text | PDF Mouse model of dominant Ullrich congenital muscular dystrophy (UCMD) doi:10.1038/scibx.2014.382 A mouse model of dominant UCMD with deletion of collagen type VI α3 (Col6a3) exon 16 could help identify treatments for the disease. Full Text | PDF Drug delivery Top Engineered, zinc finger domain–containing recombinases for site-specific delivery of therapeutic genes doi:10.1038/scibx.2014.383 An engineered recombinase could enable nontoxic, site-specific delivery of therapeutic genes to the human genome. Full Text | PDF Drug platforms Top Crystal structure of metabotropic glutamate receptor subtype 1 (mGluR1; GRM1) doi:10.1038/scibx.2014.384 The crystal structure of mGluR1 could help researchers design mGluR1-targeted therapeutics to treat cancer and various neurological indications. Full Text | PDF Hexamer-forming mAbs that activate the complement system doi:10.1038/scibx.2014.385 mAbs engineered with mutations that promote hexamer formation could help treat infections and cancer by activating the complement system. Full Text | PDF Mouse cardiomyocytes generated from fibroblasts with one pluripotency factor and four small molecules doi:10.1038/scibx.2014.386 Cell culture studies suggest cardiomyocytes for use in pharmacological screening and regenerative therapies could be generated with minimal genetic manipulation. Full Text | PDF Imaging Top Multiplexed ion beam imaging (MIBI) for detection of up to 100 target proteins in clinical samples doi:10.1038/scibx.2014.387 Imaging studies suggest MIBI could simultaneously detect up to 100 antigen targets for clinical diagnostics. Full Text | PDF Markers Top Fluorescent antibodies to membrane-bound tumor necrosis factor (mTNF) as a predictive biomarker for therapeutic responders doi:10.1038/scibx.2014.388 Fluorescent antibodies against mTNF could provide an in vivo molecular diagnostic for predicting response to anti-TNF treatment in Crohn's disease. Full Text | PDF Top

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