SciBX: Science-Business eXchange Contents: October 3 2013, Volume 6 / Issue 38

TABLE OF CONTENTS October 3 2013, Volume 6 / Issue 38 Analysis Cover Story Targets and Mechanisms Translational Notes The Distillery: Therapeutics Autoimmune disease Cancer Gastrointestinal disease Infectious disease Neurology Renal disease The Distillery: Techniques Assays and screens Chemistry Disease models Drug delivery Drug platforms Imaging Advertisement Biopharma Dealmakers A supplement to Nature Biotechnology and Nature Reviews Drug Discovery Check out the latest issue of Biopharma Dealmakers, which includes the following features: - Diseases related to the immune system touch off a spectrum of valuable business models - Oncology patent cliff makes way for younger biotechs  Click here to read the issue for FREE! SciBX: Science-Business eXchange Collection on Antibiotic Resistance This special Collection from SciBX: Science-Business eXchange provides an overview of the state of affairs on antibiotic resistance from the scientific, business and regulatory perspectives.  Click here to access the Collection for free! Produced with support from: Cempra Inc., Cubist Pharmaceuticals Inc., Durata Therapeutics Inc., Polyphor Ltd.   Analysis Cover Story Top Escaping abiraterone Lauren Martz doi:10.1038/scibx.2013.1049 Although a lot is known about how castration-resistant prostate cancers become refractory to second-generation androgen receptor antagonists, the mechanism behind resistance to CYP17 inhibitors remains a mystery. An alternative androgen synthesis pathway identified by a team from the Cleveland Clinic may change the game. Full Text | PDF Targets and Mechanisms Top Alternative strategies in ALS C. Simone Fishburn doi:10.1038/scibx.2013.1050 Biogen Idec and Evotec are pursuing distinct strategies to find new therapies for ALS. Biogen Idec is forming partnerships to understand the basic biology, whereas Evotec is partnering for a phenotypic screening approach that circumvents the need for mechanistic understanding. Full Text | PDF Translational Notes Top The Broad's outlook in cancer Michael J. Haas doi:10.1038/scibx.2013.1051 When the Broad Institute launched its Center for the Science of Therapeutics to develop new therapies, it lacked funds to take discoveries all the way to approval. A new collaboration with Bayer fills that gap for cancer assets. Full Text | PDF Advancing AD Lev Osherovich doi:10.1038/scibx.2013.1052 The NIH has made a trio of grants to academics to develop a systems biology picture of Alzheimer's disease. The teams hope to uncover new mechanisms and targets that may have been overlooked because of the field's traditional focus on β-amyloid. Full Text | PDF Distillery: Therapeutics Autoimmune disease Top IL-27 doi:10.1038/scibx.2013.1053 Studies in cell culture and mice suggest IL-27-conditioned dendritic cells (DCs) could help treat MS. Full Text | PDF Cancer Top Wolf-Hirschhorn syndrome candidate 1 (WHSC1; MMSET; NSD2) doi:10.1038/scibx.2013.1054 Cell culture studies suggest inhibiting MMSET could help treat patients carrying activating mutations in the protein. Full Text | PDF Chemokine CXC motif ligand 10 (CXCL10; IP-10) doi:10.1038/scibx.2013.1055 In vitro and mouse studies suggest antibodies targeting CXCL10 could help treat breast cancer. Full Text | PDF Thioesterase superfamily member 4 (THEM4; CTMP) doi:10.1038/scibx.2013.1056 Studies in cell culture, mice and human tissue samples suggest inhibiting CTMP could help treat breast cancer. Full Text | PDF β-Catenin (CTNNB1); B cell lymphoma 2 (BCL-2; BCL2); AXIN1; casein kinase 1α (CSNK1A1; CKI-α) doi:10.1038/scibx.2013.1057 In vitro studies suggest mutations in CTNNB1 or in genes regulating its degradation may predict tumor responses to BCL2 inhibitors. Full Text | PDF Heat shock protein 90 (Hsp90); heat shock 90 kDa protein β1 (Hsp90B1; GP96; GRP94) doi:10.1038/scibx.2013.1058 In vitro studies identified a purine-based specific inhibitor of the Hsp90 family protein GRP94 that could treat cancer. Full Text | PDF Histone deacetylase 6 (HDAC6) doi:10.1038/scibx.2013.1059 In vitro, cell culture and mouse studies have identified an HDAC6 inhibitor that could help treat cancer. Full Text | PDF Protein phosphatase 2 (PPP2CA; PP2A) doi:10.1038/scibx.2013.1060 Studies in patient samples and mice suggest Gilenya fingolimod and nonimmunosuppressive derivatives could help eradicate leukemic stem cells in CML, which are associated with disease relapse. Full Text | PDF BRAF; neuroblastoma Ras viral (v-Ras) oncogene (NRAS) doi:10.1038/scibx.2013.1061 In vitro and mouse studies have identified a pan-Raf kinase inhibitor that could help treat BRAF- or NRAS-mutant melanoma. Full Text | PDF Neuronal precursor cell expressed developmentally downregulated 8 (NEDD8); cullin 4A (CUL4A) doi:10.1038/scibx.2013.1062 Cell culture and human tissue studies suggest inhibiting CUL4A could help treat ovarian cancer. Full Text | PDF Epidermal growth factor receptor (EGFR); HER2 (EGFR2; ErbB2; neu) doi:10.1038/scibx.2013.1063 Mouse studies identified combinations of antibodies targeting HER2 and EGFR that could help treat pancreatic cancer. Full Text | PDF Gastrointestinal disease Top CD38 doi:10.1038/scibx.2013.1064 Cell culture and mouse studies suggest antagonizing CD38 could be useful for treating pancreatitis. Full Text | PDF Infectious disease Top IL-6 signal transducer (IL-6ST; gp130; CD130); IL-27; IL-27 receptor-α (IL27RA) doi:10.1038/scibx.2013.1065 Mouse studies suggest increasing IL-27 signaling through gp130 and IL27RA could help control chronic viral infections. Full Text | PDF Neurology Top β-Amyloid (Aβ) doi:10.1038/scibx.2013.1066 In vitro studies identified synthetic peptides derived from Russell's viper venom that could help treat AD. Full Text | PDF Calcium release–activated calcium channel (CRAC) doi:10.1038/scibx.2013.1067 Cell culture studies suggest agonizing CRAC could be useful for treating AD. Full Text | PDF NMDA receptor NR1 subtype (GRIN1; NR1); GRIN2B (NR2B); GABAA receptor α1 (GABRA1); GABAA receptor β3 (GABRB3) doi:10.1038/scibx.2013.1068 Human genome sequencing studies suggest modulating GABAA receptors and NMDARs could help treat some patients with pediatric epilepsy. Full Text | PDF Orexin 2 receptor (HCRTR2; OX2R) doi:10.1038/scibx.2013.1069 In vitro and mouse studies identified an OX2R-selective antagonist that may help treat insomnia. Full Text | PDF Not applicable doi:10.1038/scibx.2013.1070 Rodent studies suggest peritoneal dialysis could help decrease tissue damage after stroke. Full Text | PDF Renal disease Top Chemokine CX3C motif receptor 1 (CX3CR1) doi:10.1038/scibx.2013.1071 Mouse studies suggest inhibiting CX3CR1 could help treat glomerulonephritis. Full Text | PDF Distillery: Techniques Assays and screens Top Assay for single-cell DNA methylation analysis doi:10.1038/scibx.2013.1072 An assay for single-cell DNA methylation analysis could be useful for understanding the heterogeneity of epigenetic modifications in diseased tissue. Full Text | PDF Low-copy piggyBac (PB) mutagenesis screening to identify mutated genes that drive cancer doi:10.1038/scibx.2013.1073 Low-copy PB screening in mice could help identify genes that drive cancer when mutated. Full Text | PDF Chemistry Top Using metrics other than IC50 to assess cancer drug response doi:10.1038/scibx.2013.1074 An analysis of cellular responses to cancer drugs suggests parameters other than potency should be considered when evaluating their efficacy. Full Text | PDF Disease models Top Doxycycline-inducible adipocyte labeling system for in vivo adipogenesis monitoring doi:10.1038/scibx.2013.1075 A doxycycline-inducible adipocyte labeling system in mice could be useful for studying and monitoring adipogenesis. Full Text | PDF Interferon regulatory factor 4 (Irf4)-deficient mouse models of chronic lymphocytic leukemia (CLL) doi:10.1038/scibx.2013.1076 Irf4-deficient mice could be used to study CLL pathogenesis. Full Text | PDF Mouse model of phosphoinositide 3-kinase catalytic subunit α-polypeptide (PIK3CA; p110α)-mutant, HER2 (EGFR2; ErbB2; neu)+ breast cancer doi:10.1038/scibx.2013.1077 A mouse model of HER2+ breast cancer with a PIK3CA mutation could be useful for developing combination therapies to treat the disease. Full Text | PDF Drug delivery Top Safety mechanism assisted by the repressor of tetracycline (SMART) oncolytic Vaccinia vaccines doi:10.1038/scibx.2013.1078 Cell-based and mouse studies suggest tetracycline-inducible expression of interferon-γ (IFNG; IFN-γ) could improve the safety of Vaccinia virus (VACV)-based oncolytic viral therapy. Full Text | PDF Drug platforms Top Locus-specific control of histone modification using transcription activator–like (TAL) effector repeat fusion proteins doi:10.1038/scibx.2013.1079 TAL effector repeats linked to chromatin-modifying enzymes could enable locus-specific chromatin modification and inform epigenetic drug development. Full Text | PDF Mice overexpressing kidney injury molecule 1 (Kim-1) to model chronic kidney disease (CKD) doi:10.1038/scibx.2013.1080 Mice that chronically overexpress Kim-1 in renal epithelial cells could be used to model human CKD pathology. Full Text | PDF Imaging Top Combined microscopy system to image tumors during tissue-conserving surgery doi:10.1038/scibx.2013.1081 A combined autofluorescence and Raman scattering microscopy system could help with the rapid identification of tumor regions during tissue-conserving surgery without a tissue preparation step. Full Text | PDF Secondary Cherenkov–induced fluorescence imaging (SCIFI) to detect markers of disease activity doi:10.1038/scibx.2013.1082 Mouse studies suggest SCIFI could help detect and monitor markers of disease activity. 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