SciBX: Science-Business eXchange Contents: September 5 2013, Volume 6 / Issue 34

TABLE OF CONTENTS September 5 2013, Volume 6 / Issue 34 Analysis Cover Story Targets and Mechanisms The Distillery: Therapeutics Cancer Cardiovascular disease Infectious disease Neurology Other Transplantation The Distillery: Techniques Chemistry Disease models Drug platforms Imaging Markers Advertisement Biopharma Dealmakers A supplement to Nature Biotechnology and Nature Reviews Drug Discovery  The September 2013 issue of Biopharma Dealmakers showcases companies with partnering opportunities. This week, find out about how you can collaborate with Bavarian Nordic, Inc. 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 Post-translational mAbs Kai-Jye Lou doi:10.1038/scibx.2013.913 UCSF researchers have developed a platform capable of producing mAbs that target post-translational modifications such as phosphorylation. The technology could open up a host of new targets for cancer and other diseases associated with aberrant modifications. Next, the team will have to show that the mAbs target endogenous proteins in vivo. Full Text | PDF Targets and Mechanisms Top lncRNA meets the androgen receptor Chris Cain doi:10.1038/scibx.2013.914 The identification of two long noncoding RNAs that act directly on the androgen receptor and are required for castration-resistant prostate cancer growth provide new targets for the disease. The results also illustrate a previously unknown mechanism of action for lncRNAs. Full Text | PDF Ex-SASP-erating cancer Michael J. Haas doi:10.1038/scibx.2013.915 German researchers have identified a hypermetabolic phenotype in senescent tumor cells that exerts tumorigenic effects on other cells in the tumor microenvironment. Although small molecule inhibitors of the phenotype improved survival in a mouse model of lymphoma, future studies will need to determine whether the phenotype occurs in primary tumors. Full Text | PDF Epilepsy narrows down Lev Osherovich doi:10.1038/scibx.2013.916 A spate of human genetic studies has identified mutations in NMDAR subunits as a root cause of idiopathic focal epilepsy, a common childhood form of the disease. The studies suggest that a group of epilepsies and encephalopathies marked by seizures, aphasia and learning disorders could be treated with NMDAR-selective modulators. Full Text | PDF Distillery: Therapeutics Cancer Top Epidermal growth factor receptor (EGFR); Janus kinase-2 (JAK-2); PTEN (MMAC1; TEP1) doi:10.1038/scibx.2013.917 In vitro and mouse studies suggest allosteric inhibition of JAK-2 could help treat glioblastoma multiforme (GBM). Full Text | PDF Src; epidermal growth factor receptor 1 (EGFR1; HER1; ErbB1); HER2 (EGFR2; ErbB2; neu) doi:10.1038/scibx.2013.918 Human tumor and mouse studies suggest Src inhibitors could help treat brain metastases from breast cancer. Full Text | PDF c-Myc (MYC); mammalian target of rapamycin (mTOR; FRAP; RAFT1); 3-phosphoinositide dependent protein kinase-1 (PDPK1); polo-like kinase 1 (PLK1; STPK13) doi:10.1038/scibx.2013.919 Cell culture and mouse studies suggest combining PLK1 and mTOR inhibitors could help treat MYC-driven cancers. Full Text | PDF Epidermal growth factor receptor (EGFR); heat shock protein 90 (Hsp90) doi:10.1038/scibx.2013.920 In vitro studies identified a peptide fragment from EGFR that could help treat cancer. Full Text | PDF Not applicable doi:10.1038/scibx.2013.921 Cell culture and mouse studies suggest inhibiting glucose transporters, glycolysis or autophagy could help eliminate senescent cancer cells. Full Text | PDF R-spondin 1 (RSPO1); slit homolog 2 (SLIT2) doi:10.1038/scibx.2013.922 Mouse studies suggest RSPO1 and SLIT2 could improve the tolerability of chemoradiotherapy, which is known to damage normal intestinal tissues. Full Text | PDF S-phase kinase-associated protein 2 (SKP2) doi:10.1038/scibx.2013.923 In vitro, cell culture and mouse studies identified SKP2 inhibitors that could be useful for treating cancer. Full Text | PDF VEGF receptor 1 (FLT1; VEGFR-1) doi:10.1038/scibx.2013.924 In vitro and mouse studies suggest increasing monocyte production of soluble FLT1 could enhance the effects of therapeutic antibodies against cancer. Full Text | PDF Histone deacetylase 10 (HDAC10) doi:10.1038/scibx.2013.925 Patient tissue and mouse studies suggest increasing HDAC10 activity could help prevent cervical cancer metastasis. Full Text | PDF Prostate cancer non-coding RNA 1 (PRNCR1); prostate-specific transcript 1 (PCGEM1) doi:10.1038/scibx.2013.926 In vitro, cell culture and mouse studies suggest inhibiting the long noncoding RNAs (lncRNAs) PRNCR1 or PCGEM1 could help treat prostate cancer. Full Text | PDF Procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2); hypoxia-inducible factor 1α (HIF1A; HIF1α) doi:10.1038/scibx.2013.927 Studies in human samples and mice suggest inhibiting PLOD2 could help prevent metastasis in patients with sarcoma. Full Text | PDF Cardiovascular disease Top BET bromodomain doi:10.1038/scibx.2013.928 Cell culture and rodent studies suggest BET bromodomain inhibitors could help treat heart failure. Full Text | PDF Infectious disease Top CD4; HIV gp120 doi:10.1038/scibx.2013.929 In vitro studies suggest bispecific antibodies targeting CD4 and gp120 could be useful for treating HIV infection. Full Text | PDF Neurology Top β-Amyloid (Aβ); β-site APP-cleaving enzyme 1 (BACE1); mammalian target of rapamycin (mTOR; FRAP; RAFT1) doi:10.1038/scibx.2013.930 Mouse and cell culture studies suggest the plant-derived compound arctigenin could help treat AD. Full Text | PDF NMDAR doi:10.1038/scibx.2013.931 Rat studies suggest D-serine could help treat epilepsy. Full Text | PDF Adenosine monophosphate deaminase 2 (AMPD2) doi:10.1038/scibx.2013.932 In vitro and genetic studies identified a subset of patients with pontocerebellar hypoplasia (PCH) who could benefit from treatment with purine precursors. Full Text | PDF Parathyroid hormone 2 (PTH2; TIP39); PTH2 receptor (PTH2R) doi:10.1038/scibx.2013.933 Mouse studies suggest antagonizing PTH2R could help treat chronic pain. Full Text | PDF Matrix metalloproteinase 9 (MMP9) doi:10.1038/scibx.2013.934 Mouse studies suggest antagonizing MMP9 in combination with physical therapy could be useful for treating SCI. Full Text | PDF Other Top Neurotrophic tyrosine kinase receptor 2 (NTRK2; TrkB) doi:10.1038/scibx.2013.935 In vitro and mouse studies suggest TrkB agonists could help treat hearing loss. Full Text | PDF Transplantation Top Protein kinase Cα (PRKCA); protein kinase Cθ (PRKCQ) doi:10.1038/scibx.2013.936 Mouse studies suggest dual inhibition of PRKCA and PRKCQ could help prevent GvHD. Full Text | PDF Distillery: Techniques Chemistry Top Biosynthesis of GE2270 and derivatives in Nonomuraea doi:10.1038/scibx.2013.937 Biosynthesis of GE2270 in a strain of Nonomuraea bacteria could lead to the development of improved methods for synthesizing the thiopetide macrocycle and creating derivatives. Full Text | PDF Fourteen-step synthesis of ingenol to aid analog design doi:10.1038/scibx.2013.938 A 14-step process for ingenol synthesis could facilitate the generation of analogs for therapeutic evaluation. Full Text | PDF Disease models Top Mouse model of atopic dermatitis–like inflammation doi:10.1038/scibx.2013.939 A transgenic mouse model of atopic dermatitis could be useful for studying disease pathogenesis and identifying new treatments for the condition. Full Text | PDF Mouse model of sympathetic nervous system activation in metabolic syndrome doi:10.1038/scibx.2013.940 A new mouse model could help guide development of therapies that target the sympathetic nervous system in metabolic syndrome. Full Text | PDF Transgenic, humanized mouse model of HCV infection doi:10.1038/scibx.2013.941 Partially immunocompromised, humanized mice could be used as a model of HCV infection to help evaluate antiviral drug candidates. Full Text | PDF Drug platforms Top 2′-O-methyltransferase–deficient, live, attenuated dengue virus vaccine doi:10.1038/scibx.2013.942 2′-O-methyltransferase–deficient dengue virus could be used to develop live, attenuated vaccines against the infection. Full Text | PDF Small molecules that prevent teratoma formation in human pluripotent stem cell–derived therapies doi:10.1038/scibx.2013.943 Small molecules that are selectively toxic to human pluripotent stem cells could help decrease the tumorigenicity risk of stem cell–derived therapies. Full Text | PDF Transcription activator-like effector nucleases (TALENs) to eliminate mitochondria-specific mutant DNA doi:10.1038/scibx.2013.944 TALENs could be useful for treating mitochondrial disease by selectively removing mutant mitochondrial DNA (mtDNA). Full Text | PDF Imaging Top Noninvasive, 3D imaging of retinal and choroidal vasculature using phase-variance optical coherence tomography doi:10.1038/scibx.2013.945 A noninvasive method to image vasculature in the eye could help monitor treatment responses and diagnose patients who have age-related macular degeneration (AMD) and other choroidal vascular diseases. Full Text | PDF Markers Top Ribosomal protein S6 kinase (RSK) phosphorylation to predict response to BRAF, MEK or phosphoinositide 3-kinase (PI3K) inhibitors doi:10.1038/scibx.2013.946 Studies in patient samples, cell culture and mice suggest RSK phosphorylation status could predict response to BRAF, MEK or PI3K inhibitors. Full Text | PDF Top Advertisement Nature Publishing Group and Relay Technology Management present: The Epigenetics Target Explorer  Click here to access this free online tool and the accompanying article in Nature Reviews Drug Discovery.

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