SciBX: Science-Business eXchange Contents: March 27 2014, Volume 7 / Issue 12

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TABLE OF CONTENTS March 27 2014, Volume 7 / Issue 12 Analysis Cover Story Translational Notes Targets and Mechanisms The Distillery: Therapeutics Autoimmune disease Cancer Cardiovascular disease Dermatology Endocrine/metabolic disease Hematology Infectious disease Inflammation Musculoskeletal disease Pulmonary disease Various The Distillery: Techniques Assays and screens Chemistry Computational models Drug platforms 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 AnaptysBio Inc.   Analysis Cover Story Top A bitter taste for sinus infections Lauren Martz doi:10.1038/scibx.2014.331 A University of Pennsylvania study has shown that bitter taste agonists stimulate the release of antimicrobial peptides in the sinuses, suggesting a new way to treat chronic rhinosinusitis. Although taste receptor–targeted therapies could decrease antibiotic use, pinpointing the right receptor for each infection might be difficult. Full Text | PDF Translational Notes Top Explaining the exceptions Chris Cain doi:10.1038/scibx.2014.332 The identification of activating mutations in mTOR that explain an exceptional response in a patient with bladder cancer is the latest example of mechanistic insights that can be gleaned from analyzing exceptional responders in otherwise failed trials. The NCI plans to sequence 100 such exceptional responders to help identify other cancer-related mutations that could predict drug response. Full Text | PDF SPARKs and Catalysts C. Simone Fishburn doi:10.1038/scibx.2014.333 Although public-private partnerships and tech transfer offices provide paths for commercializing academic discoveries, many ideas languish because researchers lack the experience to navigate translation. Several universities are starting programs that help, but bridging the mindset differences between academia and industry is challenging. Full Text | PDF Targets and Mechanisms Top Insight into ependymoma Tracey Baas doi:10.1038/scibx.2014.334 Two independent studies have revealed targets for previously intractable ependymoma tumors: a fusion protein and epigenetic modifiers, respectively. The therapeutic potential of the targets remains to be established. Full Text | PDF Distillery: Therapeutics Autoimmune disease Top Adenosine A2A receptor (ADORA2A) doi:10.1038/scibx.2014.335 In vitro and mouse studies suggest conjugating an ADORA2A agonist to IgG Fc could improve stability in treating autoimmune diseases. Full Text | PDF Cancer Top Bromodomain containing 4 (BRD4); notch 1 (NOTCH1) doi:10.1038/scibx.2014.336 Mouse and cell culture studies suggest combined inhibition of BRD4 and NOTCH1 could help treat T cell ALL. Full Text | PDF FMS-like tyrosine kinase 3 (FLT3; CD135) doi:10.1038/scibx.2014.337 In vitro and mouse studies suggest the selective small molecule FLT3 inhibitor G-749 could help treat AML with resistance mutations in FLT3. Full Text | PDF BRAF V600E; epidermal growth factor receptor (EGFR) doi:10.1038/scibx.2014.338 In vitro studies identified dual inhibitors of BRAF V600E and EGFR that could treat BRAF-mutant cancers resistant to BRAF inhibitors. Full Text | PDF Mammalian target of rapamycin (mTOR; FRAP; RAFT1) doi:10.1038/scibx.2014.339 Studies in patient samples suggest mTOR inhibitors could help treat patients harboring activating mutations in mTOR. Full Text | PDF DnaJ (Hsp40) homolog subfamily B member 1 (DNAJB1); protein kinase cAMP-dependent catalytic-α (PRKACA) doi:10.1038/scibx.2014.340 Human sample and in vitro studies suggest inhibiting the DNAJB1-PRKACA gene fusion product could help treat fibrolamellar hepatocellular carcinoma (FL-HCC). Full Text | PDF Glucocorticoid-induced tumor necrosis factor receptor–related protein (GITR; TNFRSF18); tumor necrosis factor receptor superfamily member 4 (TNFRSF4; OX40; CD134); platelet activating factor (PAF) doi:10.1038/scibx.2014.341 Mouse studies suggest PAF inhibitors could help prevent anaphylaxis caused by therapeutic antibodies that target members of the TNFR superfamily. Full Text | PDF Heparan sulfate 6-O-sulfotransferase 1 (HS6ST1); HS6ST2 doi:10.1038/scibx.2014.342 In vitro and mouse studies suggest inhibiting HS6ST1 and HS6ST2 could help treat ovarian cancer. Full Text | PDF Cardiovascular disease Top MicroRNA-25 (miR-25) doi:10.1038/scibx.2014.343 Patient tissue and mouse studies suggest inhibiting miR-25 could help treat heart failure. Full Text | PDF Dermatology Top Complement component 1 q subcomponent (C1Q) doi:10.1038/scibx.2014.344 Rodent studies suggest C1Q could increase angiogenesis to promote wound healing. Full Text | PDF Endocrine/metabolic disease Top Netrin 1 (NTN1); unc-5 homolog B (UNC5B; UNC5H2) doi:10.1038/scibx.2014.345 Human sample and mouse studies suggest inhibiting NTN1 or UNC5B could help treat obesity and insulin resistance. Full Text | PDF Protein arginine methyltransferase 6 (PRMT6) doi:10.1038/scibx.2014.346 In vitro and mouse studies suggest inhibiting PRMT6 could help treat obesity and type 2 diabetes. Full Text | PDF Hematology Top Complement 5 (C5) doi:10.1038/scibx.2014.347 Genetic sequencing studies identified a C5 mutation that could help predict response to Soliris eculizumab. Full Text | PDF Growth hormone 1 (GH1); thrombopoietin receptor (CD110; MPL) doi:10.1038/scibx.2014.348 In vitro and mouse studies suggest combined stimulation of MPL and GH1 could help treat thrombocytopenia. Full Text | PDF Infectious disease Top Lymphotoxin-β receptor (LTBR) doi:10.1038/scibx.2014.349 In vitro studies suggest activating LTBR could help treat HBV infection. Full Text | PDF Inflammation Top Taste receptor type 1 (TAS1R; T1R); TAS2R (T2R) doi:10.1038/scibx.2014.350 Patient sample and cell culture studies suggest agonizing bitter taste receptors (TAS2Rs) or antagonizing sweet taste receptors (TAS1Rs) could help treat chronic rhinosinusitis. Full Text | PDF Musculoskeletal disease Top Bone morphogenetic protein 2 (BMP2); platelet derived growth factor BB (PDGFBB); placental growth factor (PGF; PlGF); VEGF receptor 2 (KDR/Flk-1; VEGFR-2) doi:10.1038/scibx.2014.351 Rodent studies suggest improving extracellular matrix (ECM) binding of growth factors could improve wound healing and bone repair. Full Text | PDF Pulmonary disease Top Peroxisome proliferation–activated receptor-γ (PPARG; PPARγ) doi:10.1038/scibx.2014.352 Ex vivo and mouse studies suggest agonizing PPARγ could help treat emphysema. Full Text | PDF Various Top IL-35 doi:10.1038/scibx.2014.353 Mouse studies suggest enhancing IL-35-producing B cell activity could help treat autoimmunity, whereas blocking production could help treat infections. Full Text | PDF Distillery: Techniques Assays and screens Top Cell-based prediction of the fraction of free, unbound compound in brain tissue doi:10.1038/scibx.2014.354 A high throughput, cell-based assay could predict what fraction of a compound would be free and nonspecifically bound in brain tissue. Full Text | PDF Chemistry Top Hydrophobic cross-linking of peptides to create inhibitors of protein-protein interactions doi:10.1038/scibx.2014.355 Hydrophobic cross-linking of peptides at critical binding residues could help generate stable, peptide-based inhibitors of protein-protein interactions involving irregular, non–alpha helical interfaces. Full Text | PDF Synthetic low molecular weight heparins (LMWHs) with reversible and high anticoagulation activity doi:10.1038/scibx.2014.356 Synthetic LMWHs that have low production costs and high sensitivity to the heparin antidote protamine could be useful for treating thrombosis with enhanced safety and reduced cost. Full Text | PDF Computational models Top Rational design platform to generate dual-acting kinase and bromodomain inhibitors doi:10.1038/scibx.2014.357 In vitro studies suggest dual-acting kinase and bromodomain inhibitors can be rationally designed to treat cancer and inflammatory disease. Full Text | PDF Drug platforms Top Functional, expandable human hepatocytes obtained by direct reprogramming doi:10.1038/scibx.2014.358 Two studies suggest functional, proliferative hepatocytes generated from human fibroblasts could be used for drug testing and regenerative medicine approaches. Full Text | PDF Markers Top Morning cortisol and self-reported depression symptoms to predict risk of major depressive disorder in adolescent males doi:10.1038/scibx.2014.359 Measuring morning salivary cortisol levels in conjunction with self-reported depression symptoms could help identify adolescent males at risk of depression. Full Text | PDF Top

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