SciBX: Science-Business eXchange Contents: August 21 2014, Volume 7 / Issue 32

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TABLE OF CONTENTS August 21 2014, Volume 7 / Issue 32 Analysis Cover Story Translational Notes Targets and Mechanisms Tools The Distillery: Therapeutics Cancer Dermatology Hepatic disease Neurology Ophthalmic disease The Distillery: Techniques Assays and screens Chemistry Computational models Disease models Drug platforms Imaging Markers Advertisement Biopharma Dealmakers A supplement to Nature Biotechnology and Nature Reviews Drug Discovery The June 2014 issue of Biopharma Dealmakers showcases companies with partnering opportunities. This week, find out about how you can collaborate with Axikin Pharmaceuticals.   Analysis Cover Story Top Fat chance for cancer cachexia Lauren Martz doi:10.1038/scibx.2014.941 With no drugs on the market and a pair of recent Phase III failures in cancer-associated cachexia, companies may consider targeting the cause of the wasting disease rather than its symptoms a better therapeutic strategy. Two independent academic teams have now found evidence that browning of white fat is responsible for cachexia in patients with cancer and propose different strategies to block the process. Full Text | PDF Translational Notes Top AstraZeneca taps the Cambridge wellspring Michael J. Haas doi:10.1038/scibx.2014.942 AstraZeneca has unveiled plans for its R&D center and global headquarters in Cambridge, U.K.—the next major step in the pharma's strategy to improve pipeline productivity to help it recover growth and regain ground in scientific leadership. The company hopes to tap into world-class research through partnerships with nearby institutes. Full Text | PDF Targets and Mechanisms Top Corneal perspectives Benjamin Boettner doi:10.1038/scibx.2014.943 Two independent findings could increase the availability of tissue for corneal transplants. A UCSD team has identified key factors needed to culture the limbal stem cells necessary for clear vision. A Harvard team has found a marker for enhanced regenerative potential of limbal stem cells and licensed the antibody to stem cell companies Rheacell and Ticeba. Full Text | PDF Tools Top Circling back to basics Chris Cain doi:10.1038/scibx.2014.944 Creating potent and orally bioavailable macrocycles is more challenging than developing small molecules, but a trio of studies could close the gap by proposing new design guidelines, identifying protein-protein interfaces to target and providing a new method to synthesize cyclic peptides. Full Text | PDF Distillery: Therapeutics Cancer Top Fatty acid synthase (FASN; FAS) doi:10.1038/scibx.2014.945 Mouse studies suggest inhibiting FASN could help prevent tumor regrowth after antiangiogenic therapy. Full Text | PDF Guanine nucleotide binding protein q polypeptide (GNAQ; Gαq); MAS-related GPR member X1 (MRGPRX1; GPCR; SNSR4) doi:10.1038/scibx.2014.946 In vitro and cell culture studies suggest the small molecule compound BIM-46187 blocks pathogenic GPCR signaling by targeting the GNAQ subunit. Full Text | PDF Stem cell factor receptor tyrosine kinase (c-Kit; KIT; CD117) doi:10.1038/scibx.2014.947 In vitro studies have identified selective inhibitors of the drug-resistant c-Kit D816V mutant that could help treat cancers that have become refractory to existing kinase inhibitors. Full Text | PDF Prolactin (PRL); PRL receptor (PRLR) doi:10.1038/scibx.2014.948 In vitro and mouse studies suggest increasing PRL signaling could help prevent hepatocellular carcinoma (HCC). Full Text | PDF Adenosine A2A receptor (ADORA2A); CTLA-4 (CD152); ecto-5′-nucleotidase (NT5E; NT; CD73); programmed cell death 1 (PDCD1; PD-1; CD279) doi:10.1038/scibx.2014.949 Mouse studies suggest ADORA2A inhibitors could be repurposed to treat cancers that express CD73, which catalyzes the conversion of AMP to adenosine. Full Text | PDF Androgen receptor (AR); prostate-specific antigen (KLK3; PSA) doi:10.1038/scibx.2014.950 In vitro studies have identified indole carboxamide–based AR inhibitors that could help treat prostate cancer. Full Text | PDF Lysine-specific demethylase 4A (KDM4A; JMJD2A); KDM4B (JMJD2B) doi:10.1038/scibx.2014.951 Cell culture studies suggest inhibiting KDM4A and KDM4B could help treat prostate cancer. Full Text | PDF Dermatology Top Annexin A1 (ANXA1); formyl peptide receptor 1 (FPR1) doi:10.1038/scibx.2014.952 Cell culture studies suggest inhibiting ANXA1 or its receptor FPR1 could help treat drug-induced adverse cutaneous reactions. Full Text | PDF Olfactory receptor family 2 subfamily AT member 4 (OR2AT4) doi:10.1038/scibx.2014.953 Cell and tissue culture studies suggest activating OR2AT4 could help promote wound healing. Full Text | PDF Hepatic disease Top Periostin (POSTN) doi:10.1038/scibx.2014.954 Studies in mice and humans suggest inhibiting periostin could help treat hepatosteatosis. Full Text | PDF Neurology Top β-amyloid (Aβ) doi:10.1038/scibx.2014.955 Mouse studies suggest glycosphingolipid-enriched exosomes could help treat AD. Full Text | PDF Sphingomyelin phosphodiesterase 1 acid lysosomal (SMPD1; ASM) doi:10.1038/scibx.2014.956 Studies in mice and human samples suggest inhibition of SMPD1 could decrease AD pathology. Full Text | PDF Transient receptor potential cation channel subfamily C member 7 (TRPC7) doi:10.1038/scibx.2014.957 Mouse and cell culture studies suggest inhibiting TRPC7 could help prevent status epilepticus. Full Text | PDF Microtubule-associated protein-τ (MAPT; tau; FTDP-17) doi:10.1038/scibx.2014.958 In vitro and mouse studies suggest depleting tau deposits could help treat HD. Full Text | PDF Ophthalmic disease Top Caspase-8 (CASP8; FLICE); toll-like receptor 4 (TLR4) doi:10.1038/scibx.2014.959 Rodent studies suggest inhibiting CASP8 could help treat glaucoma. Full Text | PDF Distillery: Techniques Assays and screens Top Genomewide screen for identifying barriers to generation of human induced pluripotent stem (iPS) cells doi:10.1038/scibx.2014.960 A screen to identify barriers to the generation of human iPS cells could aid the development of optimized reprogramming protocols. Full Text | PDF Gold plasmonic chip for biomarker discovery and diagnosis of type 1 diabetes doi:10.1038/scibx.2014.961 An islet antigen microarray on a gold plasmonic chip could be useful for discovering biomarkers and diagnosing type 1 diabetes. Full Text | PDF Immunosignature diagnosis platform doi:10.1038/scibx.2014.962 Immunosignature profiles could be used to diagnose or classify various human diseases. Full Text | PDF Chemistry Top Asparagine-aspartate peptide ligase for peptide macrocyclization doi:10.1038/scibx.2014.963 An asparagine-aspartate ligase, butelase 1, could enable the synthesis of cyclic peptides with utility for drug discovery. Full Text | PDF Guidelines for the design of orally available macrocycles doi:10.1038/scibx.2014.964 A set of guidelines derived from an analysis of structures of macrocycles bound to proteins could be used to aid the design of orally bioavailable macrocycles that disrupt protein-protein interactions. Full Text | PDF Computational models Top Computational prediction of loops at protein-protein interfaces using LoopFinder doi:10.1038/scibx.2014.965 A computational approach to predict loops at protein-protein interfaces could help identify interactions amenable to pharmacological targeting. Full Text | PDF Disease models Top Calmodulin binding transcription activator 1 (Camta1)-deficient mice as a model of ataxia and neurodegenerative disease doi:10.1038/scibx.2014.966 Camta1-deficient mice could be useful for identifying and evaluating therapeutic candidates to treat ataxia and neurodegenerative diseases. Full Text | PDF Drug platforms Top Creation of biological pacemaker from ventricular myocytes doi:10.1038/scibx.2014.967 A gene therapy approach to create a temporary biological pacemaker in the heart could help patients who are contraindicated for an electronic pacemaker because of transient issues such as an active infection. Full Text | PDF HIV genome excision from host cells using guide RNA (gRNA)-directed Cas9 genome editing doi:10.1038/scibx.2014.968 In vitro studies suggest gRNA-directed Cas9 genome editing could help treat HIV. Full Text | PDF Imaging Top 3D, carbonized polyacrylonitrile scaffolds to promote bone tissue regeneration doi:10.1038/scibx.2014.969 3D, carbonized polyacrylonitrile scaffolds could be useful for promoting bone repair and regeneration. Full Text | PDF Markers Top Gastric tumor classification system doi:10.1038/scibx.2014.970 Studies in patient samples have identified a classification system for human gastric cancers that could help guide treatment decisions. Full Text | PDF Top Advertisement Biopharma Dealmakers A supplement to Nature Biotechnology and Nature Reviews Drug Discovery The June 2014 issue of Biopharma Dealmakers showcases companies with partnering opportunities. This week, find out about how you can collaborate with Amunix.

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