SciBX: Science-Business eXchange Contents: December 5 2013, Volume 6 / Issue 46

TABLE OF CONTENTS December 5 2013, Volume 6 / Issue 46 Analysis Cover Story Translational Notes Targets and Mechanisms The Distillery: Therapeutics Autoimmune disease Cancer Cardiovascular disease Endocrine/metabolic disease Infectious disease Musculoskeletal disease Neurology Various The Distillery: Techniques Assays and screens Disease models Drug delivery Drug platforms 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 QRxPharma and Boehringer Ingelheim. 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.    Analysis Cover Story Top Targeting fibrotic integrin Benjamin Boettner doi:10.1038/scibx.2013.1308 An international team of researchers has shown that the myofibroblast-expressed integrin αV subunit drives fibrosis and that a small molecule integrin αV antagonist from Antegrin Therapeutics can attenuate the process in mice. The biotech is developing an improved version of the compound for pulmonary fibrosis. Full Text | PDF Translational Notes Top A conversation with Chris Lipinski C. Simone Fishburn doi:10.1038/scibx.2013.1309 Although the 'rule of five' has altered medicinal chemistry for oral small molecule drugs, Chris Lipinski believes that predicting the behavior of newer biologics might not be far off, and optimization of RNA or protein delivery could be the opportunity for the next big breakthrough in computer-based predictions. Full Text | PDF Targets and Mechanisms Top A gut feeling about butyrate Tracey Baas doi:10.1038/scibx.2013.1310 Inflammatory conditions of the gut have long been associated with imbalances in mucosal levels of microflora-produced short-chain fatty acids, but the underlying mechanisms were unknown. Two separate groups in the U.S. and Japan have reported how one such bacterial fatty acid can promote mucosal health. Full Text | PDF Distillery: Therapeutics Autoimmune disease Top Forkhead box P3 (FOXP3) doi:10.1038/scibx.2013.1311 Cell culture and mouse studies suggest butyrylated compounds could be used to treat colitis or other autoimmune diseases. Full Text | PDF Cancer Top MicroRNA-141 (miR-141); miR-219 doi:10.1038/scibx.2013.1312 Cell culture and mouse studies suggest miR-141 and miR-219 could help prevent bone metastases. Full Text | PDF DNA doi:10.1038/scibx.2013.1313 Mouse and cell culture studies suggest a mitochondria-targeted triphenylphosphonium derivative of the nitrogen mustard chlorambucil could help treat breast and pancreatic cancers. Full Text | PDF Toll-like receptor 9 (TLR9); signal transducer and activator of transcription 3 (STAT3) doi:10.1038/scibx.2013.1314 Mouse studies suggest inhibitors of TLR9 or STAT3 could help prevent tumor recurrence after radiation therapy. Full Text | PDF Tubulin doi:10.1038/scibx.2013.1315 In vitro and mouse studies have identified aryloxazole-based tubulin inhibitors that could help treat cancer. Full Text | PDF BCR-ABL tyrosine kinase; macrophage inflammatory protein-1α (CCL3; MIP1A) doi:10.1038/scibx.2013.1316 Mouse studies suggest inhibiting CCL3 signaling could help treat CML. Full Text | PDF Discoidin domain receptor tyrosine kinase 1 (DDR1) doi:10.1038/scibx.2013.1317 In vitro studies suggest inhibiting DDR1 could help increase the efficacy of chemotherapeutics in Hodgkin's lymphoma. Full Text | PDF UDP glucuronosyltransferase 2 family polypeptide B15 (UGT2B15) doi:10.1038/scibx.2013.1318 Patient and cell culture studies suggest activating UGT2B15 could help treat prostate cancer. Full Text | PDF Cardiovascular disease Top Fatty acid amide hydrolase (FAAH) doi:10.1038/scibx.2013.1319 Mouse studies suggest inhibiting anandamide signaling through FAAH could help treat or prevent pulmonary hypertension. Full Text | PDF Endocrine/metabolic disease Top Adiponectin (ADIPOQ); adiponectin receptor 1 (ADIPOR1); ADIPOR2 doi:10.1038/scibx.2013.1320 Mouse studies suggest a dual ADIPOR1 and ADIPOR2 agonist could help treat obesity and type 2 diabetes. Full Text | PDF Patatin-like phospholipase domain containing 2 (PNPLA2; ATGL) doi:10.1038/scibx.2013.1321 In vitro and mouse studies have identified an inhibitor of ATGL that might help treat dyslipidemia and metabolic disorders. Full Text | PDF Infectious disease Top Tubulin doi:10.1038/scibx.2013.1322 In vitro and mouse studies have identified a class of tubulin inhibitors that could help treat parasitic infections. Full Text | PDF Dengue virus envelope protein E (DENV_gp1) doi:10.1038/scibx.2013.1323 In vitro studies have identified residues of the dengue virus envelope protein that could be targeted to treat dengue fever. Full Text | PDF HIV gp120 doi:10.1038/scibx.2013.1324 Nonhuman primate studies suggest the broadly neutralizing, anti–HIV gp120 mAb PGT121 could be used to treat HIV infection. Full Text | PDF HIV gp120 doi:10.1038/scibx.2013.1325 Nonhuman primate studies suggest combining the anti–HIV gp120 mAbs 3BNC117 and 10-1074 could help treat HIV infection. Full Text | PDF Musculoskeletal disease Top TNF-like weak inducer of apoptosis (TWEAK) doi:10.1038/scibx.2013.1326 In vitro and mouse studies suggest inhibiting TWEAK could promote muscle regeneration after injury. Full Text | PDF Neurology Top α-Synuclein (SNCA); NEDD4 family E3 ubiquitin protein ligase (RSP5); neural precursor cell expressed developmentally downregulated 4 (NEDD4; NEDD4-1) doi:10.1038/scibx.2013.1327 In vitro and ex vivo studies identified an N-arylbenzimidazole (NAB) that could help treat PD. Full Text | PDF Various Top Factor Xa; factor XIa; kallikrein doi:10.1038/scibx.2013.1328 In vitro and rodent studies suggest desmolaris, a protein from vampire bat saliva, could help treat inflammation and thrombosis. Full Text | PDF Integrin αV (CD51) doi:10.1038/scibx.2013.1329 Studies in mice suggest a small molecule inhibitor of CD51 could help treat fibrosis. Full Text | PDF Distillery: Techniques Assays and screens Top In vitro screening for genetic signatures associated with sensitivity to targeted cancer therapeutics doi:10.1038/scibx.2013.1330 Combined genetic and chemical screening of lung cancer cells for altered genetic signatures could reveal sensitivity to therapeutic candidates. Full Text | PDF Leukemia-stroma coculture system to screen for selective inhibitors of leukemia stem cells (LSCs) doi:10.1038/scibx.2013.1331 A leukemia-stroma coculture system could be used in high throughput screens for compounds that selectively inhibit LSCs. Full Text | PDF Radiohalogen label for improved tracking of therapeutic antibodies in vivo doi:10.1038/scibx.2013.1332 An 125I-based radiohalogen probe with improved cell retention could aid preclinical biodistribution studies of therapeutic mAbs. Full Text | PDF Disease models Top Mouse model of intrahepatic cholangiocarcinoma (ICC) doi:10.1038/scibx.2013.1333 Orthotopic allograft mouse models of ICC could be used to validate drivers ofthe disease. Full Text | PDF Drug delivery Top Nanoparticle-mediated co-delivery of small interfering RNA and cisplatin prodrug doi:10.1038/scibx.2013.1334 Engineered, self-assembling nanoparticles that co-deliver siRNA and a cisplatin prodrug could improve cancer chemotherapy response. Full Text | PDF Drug platforms Top Expandable and transplantable fetal intestinal progenitors with colon-regenerative potential doi:10.1038/scibx.2013.1335 Intestinal progenitor cells with fetal characteristics could be used to repair injured colon epithelium. Full Text | PDF Immunosupression regimen to prevent immunotoxin neutralization doi:10.1038/scibx.2013.1336 A small clinical study suggests combining the immunosuppressive drugs pentostatin and cyclophosphamide could prevent neutralizing antibodies against immunotoxin treatment in cancer. Full Text | PDF Top

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