SciBX: Science-Business eXchange Contents: October 17 2013, Volume 6 / Issue 40

TABLE OF CONTENTS October 17 2013, Volume 6 / Issue 40 Analysis Cover Story Translational Notes Targets and Mechanisms The Distillery: Therapeutics Cancer Cardiovascular disease Endocrine/metabolic disease Hepatic disease Infectious disease Musculoskeletal disease Neurology Ophthalmic disease The Distillery: Techniques Assays and screens Chemistry Disease models Drug delivery Drug platforms Imaging Markers 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 Revving up cGAS Chris Cain doi:10.1038/scibx.2013.1117 University of Texas Southwestern Medical Center researchers have confirmed the role of cyclic AMP-GMP signaling in the innate immune system, making a case for developing adjuvants that agonize the pathway or antagonists of the pathway to treat autoimmune conditions. Full Text | PDF Translational Notes Top Clinical takeoff for new epigenetic targets Kai-Jye Lou doi:10.1038/scibx.2013.1118 Next year is expected to be a banner year for next-generation epigenetics companies, with key clinical data expected for next-generation drugs and first-generation candidates. Big biotech and pharma companies that carved up the space in recent years might have clinical data even sooner. Full Text | PDF Targets and Mechanisms Top HER2's outside help Lev Osherovich doi:10.1038/scibx.2013.1119 An international team has found that neurokinin 1 substance P receptor, a known player in nausea, pain and inflammation, enhances HER2 signaling in breast cancer. The findings argue for combining antagonists against both receptors to treat cancer. Full Text | PDF sFGFR for achondroplasia Lauren Martz doi:10.1038/scibx.2013.1120 French researchers have designed a decoy version of fibroblast growth factor receptor 3 that increased bone length and decreased achondroplasia-associated complications in mice compared with vehicle. The molecule has a longer half-life than other clinical dwarfism candidates focused on correcting abnormal signaling by the receptor. Full Text | PDF Distillery: Therapeutics Cancer Top Neurokinin 1 substance P (TAC1; NK1); NK1 substance P receptor (TACR1); HER2 (EGFR2; ErbB2; neu) doi:10.1038/scibx.2013.1121 Studies in cell culture and mice suggest antagonizing NK1 or TACR1 could be useful for treating HER2+ breast cancer. Full Text | PDF Retinoic acid receptor responder (tazarotene induced) 1 (RARRES1; TIG1); AXL receptor tyrosine kinase (AXL; UFO) doi:10.1038/scibx.2013.1122 In vitro and mouse studies suggest inhibiting TIG1 could help treat inflammatory breast cancer. Full Text | PDF MHC class I polypeptide–related sequence B (MICB); killer cell lectin-like receptor subfamily K member 1 (KLRK1; CD314; NKG2D) doi:10.1038/scibx.2013.1123 Mouse studies suggest reducing circulating MICB levels could help treat cancer. Full Text | PDF 3-Phosphoinositide–dependent protein kinase-1 (PDPK1); BRAF doi:10.1038/scibx.2013.1124 Studies in patient tumor samples and mice suggest PDPK1 inhibitors could help treat melanoma. Full Text | PDF Cardiovascular disease Top MicroRNA-27a (miR-27a); VE-cadherin (CD144; cadherin-5) doi:10.1038/scibx.2013.1125 Mouse studies suggesting blocking the interaction between miR-27a and VE-cadherin transcripts could help treat ischemia. Full Text | PDF Endocrine/metabolic disease Top Hypoxia-inducible factor prolyl hydroxylase 3 (EGLN3; HIF-PH3; PHD3) doi:10.1038/scibx.2013.1126 Mouse studies suggest liver-specific inhibition of PHD3 could help treat type 2 diabetes without the toxicity of pan-PHD inhibition. Full Text | PDF K(lysine) acetyltransferase 2B (KAT2B; PCAF) doi:10.1038/scibx.2013.1127 Mouse studies suggest antagonizing KAT2B could help lower glucose levels and help treat type 2 diabetes. Full Text | PDF Solute carrier family 30 zinc transporter member 8 (SLC30A8; ZNT8) doi:10.1038/scibx.2013.1128 Mouse and human studies suggest stimulating pancreatic SLC30A8 could help treat diabetes. Full Text | PDF Adenosine A2A receptor (ADORA2A) doi:10.1038/scibx.2013.1129 In vitro studies suggest ADORA2A agonists could help treat Niemann-Pick disease type C1 (NPC1). Full Text | PDF Palmitoyl-protein thioesterase 1 (PPT1) doi:10.1038/scibx.2013.1130 In vitro and mouse studies suggest a hydroxylamine derivative could help treat infantile neuronal ceroid lipofuscinosis (INCL), a lysosomal storage disorder in which loss of PPT1 function leads to lysosomal ceroid accumulation and neuronal damage. Full Text | PDF Hepatic disease Top Ceramide synthase 2 (CERS2) doi:10.1038/scibx.2013.1131 Mouse studies suggest inhibiting CERS2 could help treat and prevent drug-induced liver injury. Full Text | PDF Infectious disease Top Formyl peptide receptor 1 (FPR1) doi:10.1038/scibx.2013.1132 Mouse studies suggest stimulating neutrophil-expressed FPR1 could help treat toxoplasmosis and other chronic gastrointestinal infections. Full Text | PDF Leishmania hemoglobin receptor (HbR) doi:10.1038/scibx.2013.1133 Rodent studies suggest an HbR-based vaccine could protect against visceral Leishmaniasis. Full Text | PDF Musculoskeletal disease Top Fibroblast growth factor receptor 3 (FGFR3; CD333) doi:10.1038/scibx.2013.1134 Mouse studies suggest a recombinant, soluble form of FGFR3 could help treat achondroplasia, a disorder in bone growth caused by a point mutation in FGFR3 that increases the receptor's activity. Full Text | PDF Neurology Top Nicotinic acetylcholine receptor α4β2 doi:10.1038/scibx.2013.1135 Pharmacological and rat studies suggest the sazetidine A derivative VMY-2-95 could aid smoking cessation. Full Text | PDF Dopamine D5 receptor doi:10.1038/scibx.2013.1136 Studies in rodents suggest inhibiting dopamine D5 receptor in the subthalamic nucleus (STN) could help treat PD. Full Text | PDF Ophthalmic disease Top Centrosomal protein 290 kDa (CEP290) doi:10.1038/scibx.2013.1137 Cell culture and biochemical studies suggest a truncated form of CEP290 could help treat Leber's congenital amaurosis (LCA) type 10. Full Text | PDF Angiopoietin 1 (ANG1; ANGPT1) doi:10.1038/scibx.2013.1138 Mouse studies suggest ANG1 could help treat retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR). Full Text | PDF Distillery: Techniques Assays and screens Top Virus-based in vivo RNAi screens to identify host interactions doi:10.1038/scibx.2013.1139 In vitro and in vivo RNAi screens to identify virus-host interactions could help identify new targets to treat and prevent viral infections. Full Text | PDF Chemistry Top In vitro generation of branched polyketides using bacterial polyketide synthase (PKS) doi:10.1038/scibx.2013.1140 A bacterial PKS capable of generating branched polyketides may aid the synthesis of complex polyketides with therapeutic potential. Full Text | PDF Disease models Top Photoreceptors differentiated from patient keratinocyte–derived induced pluripotent stem (iPS) cells to model ophthalmic diseases doi:10.1038/scibx.2013.1141 In vitro and mouse studies suggest iPS cells derived from patient keratinocytes could be used to generate photoreceptor precursors to model or treat genetic retinal disorders. Full Text | PDF Drug delivery Top Matrix metalloproteinase 2 (MMP2)-activated, chemotherapeutic nanocarriers for targeted drug delivery doi:10.1038/scibx.2013.1142 MMP2-activated nanocarriers could provide a drug delivery vehicle for cancer chemotherapies. Full Text | PDF Tumor-specific delivery of chemotherapy using micelles with phenylboronic acid on their surface (PBA-micelles) doi:10.1038/scibx.2013.1143 Polymeric PBA-micelles could enable tumor-specific delivery of chemotherapy. Full Text | PDF Drug platforms Top Inhibition of methyl-CpG binding domain protein 3 (MBD3) for deterministic and synchronized reprogramming to pluripotency doi:10.1038/scibx.2013.1144 In vitro studies suggest depletion of Mbd3 can improve the efficiency of reprogramming somatic cells to a pluripotent state over short time periods. Full Text | PDF Stabilizing, camelid-derived nanobodies to facilitate generation of crystal structures of GPCRs bound to low-affinity, natural ligands doi:10.1038/scibx.2013.1145 Stabilizing, camelid-derived antibody fragments called nanobodies could be useful for generating the crystal structure of GPCRs bound to low-affinity, natural ligands. Full Text | PDF Synthesis of therapeutic peptides resistant to degradation by serine proteases doi:10.1038/scibx.2013.1146 A method to render therapeutic peptides resistant to serine proteases could increase their in vivo stability. Full Text | PDF Imaging Top Microtubule-associated protein-τ (MAPT; TAU; FTDP-17)-staining PET reagent for imaging Alzheimer's disease (AD) pathology doi:10.1038/scibx.2013.1147 Mouse and human studies suggest PET compounds could be useful for imaging TAU neurofibrillary tangles in AD and other tauopathies. Full Text | PDF Markers Top 2-Aminoadipic acid as a predictive marker for type 2 diabetes doi:10.1038/scibx.2013.1148 A study in humans suggests measuring concentrations of 2-aminoadipic acid in blood could help predict the risk of developing type 2 diabetes. Full Text | PDF Kaposi sarcoma–associated herpes virus (KSHV; HHV-8) as a biomarker for castration-resistant prostate cancer (CRPC) doi:10.1038/scibx.2013.1149 Cell-based studies suggest KSHV infection might serve as a marker for CRPC. Full Text | PDF Three-gene signature predictive of indolent prostate cancer doi:10.1038/scibx.2013.1150 A three-gene signature could help identify patients who have less aggressive forms of prostate cancer. 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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