Idrugs最新文献

The American Diabetes Association 70th Scientific Sessions, held in Orlando, FL, USA, included topics covering new therapeutic developments in the field of diabetes research. This conference report highlights selected presentations on new research with novel agents. Investigational drugs discussed include the glucagon-like peptide-1 (GLP-1) agonist taspoglutide (Roche Holding AG/Teijin Ltd/ Chugai Pharmaceutical Co Ltd), the GLP-1 analog SKL-18287 (Sanwa Kagaku Kenkyusho Co Ltd), the sodium glucose transporter-2 (SGLT2) inhibitor ASP-1941 (Astellas Pharma Inc/Kotobuki Pharmaceutical Co Ltd), the dual SGLT2/1 inhibitor LX-4211 (Lexicon Pharmaceuticals Inc), and the selective PPARgamma modulator INT-131 (InteKrin Therapeutics Inc).

The American Diabetes Association 70th Scientific Sessions, held in Orlando, FL, USA, included topics covering new therapeutic developments in the field of diabetes research. This conference report highlights selected presentations on new research with novel agents. Investigational drugs discussed include the glucokinase activator SKL-19014 (Sanwa Kagaku Kenkyusho Co Ltd), the GPR119 agonist AS-1535907 (Astellas Pharma Inc), the apical sodium-dependent bile transporter (ASBT) inhibitor SC-435 (Satiogen Pharmaceuticals Inc), the VEGF-A activator SB-509 (Sangamo BioSciences Inc), and the protein tyrosine phosphatase 1b (PTP-1b) antisense inhibitor ISIS-113715 (ISIS Pharmaceuticals Inc).

SMi's fifth annual ADMET Conference, held in London, included topics covering new developments in the field of ADMET. This conference report highlights selected presentations on ADME optimization in drug discovery; targeting drugs to the brain; predicting bonds that might be attacked during metabolism; treating Caco-2 membranes with vinblastine to enhance P-glycoprotein interactions; predictive ADMET in hit-to-lead optimization; structure-based studies of ADMET targets; an accelerated process for integrated drug development; building hypotheses in lead selection and optimization; supersaturation effects; the prediction of drug-drug interactions; developing a mechanism-based pharmacokinetic/pharmacodynamic model; drug transporter assays in drug discovery; time-dependent inhibition screens in early drug discovery; the system-dependent inhibition of CYP enzymes; the integrating predictive toxicology framework OpenTox; high-content analysis for predictive cytotoxicity testing; and emerging in vitro toxicity assays.

The API Global Sourcing Strategies 2010 Conference, held in Berlin, included topics covering new developments in the field of global sourcing of active pharmaceutical ingredients (APIs). This conference report highlights selected presentations on development in Eastern API markets, specifically India and China, factors influencing changes in global API sourcing, and risk mitigation in API sourcing.

The American Society for Virology 29th Annual Meeting, held in Bozeman, MT, USA, included topics covering new vaccine technologies, delivery methods and treatments in the field of virology. This conference report highlights selected presentations on human norovirus (HuNoV), SARS coronavirus and Rift Valley fever virus vaccine technologies; programmed cell death-1 (PD1) blockade and HyperAcute alpha-Gal platform technology methods; aerosol vaccination delivery; novel technologies to produce influenza virus-like particles (VLP) in mammalian cell lines; and investigational human rotavirus vaccines.

RNAi-based approaches have contributed significantly to the improved understanding of gene expression and function in vitro. The ability to apply these strategies in vivo to validate the role of specific genes in normal or pathological conditions, and to induce gene silencing, has led to new possibilities for using RNAi as a novel therapeutic modality. However, the translation of RNAi from an effective genomic tool into clinical applications has been hindered by the challenge of delivering RNAi molecules to their target tissues by systemic administration, particularly to hematopoietic cells. This feature review describes the current systemic RNAi delivery platforms targeted to leukocytes, with a focus on the integrin-targeted stabilized nanoparticles strategy, which uses leukocyte integrins for the delivery of siRNAs exclusively to cells of the immune system.

Tivozanib (AV-951; KRN-951), being developed by AVEO Pharmaceuticals Inc and Kyowa Hakko Kirin Co Ltd, is an orally active, ATP-competitive, small-molecule, quinoline-urea derivative that inhibits VEGFR tyrosine kinase for the potential treatment of cancer. In particular, tivozanib is able to markedly inhibit the ligand-induced phosphorylation of VEGFR-1, VEGFR-2 and VEGFR-3 at picomolar concentrations. In preclinical studies, tivozanib produced a significant inhibition of tumor growth and angiogenesis in several different xenograft tumor models in athymic rats. In a phase I clinical trial, tivozanib was safe and tolerable when administered at oral doses up to 1.5 mg on a schedule of 4 weeks on, 2 weeks off treatment. Results from a phase II clinical trial in patients with advanced renal cell carcinoma reported an overall response rate of 25.4% and a median progression-free survival of 11.8 months in patients treated with tivozanib as a single agent. Hypertension and dysphonia were the most frequent adverse events. At the time of publication, a phase III clinical trial was recruiting patients with advanced renal cancer to assess tivozanib in comparison with sorafenib. Clinical trials are currently ongoing to evaluate the safety and antitumor activity of tivozanib in breast, lung and colorectal cancer. Tivozanib might represent a promising anticancer agent in several different tumor types.

The International Quality & Productivity Center's (IQPC) Second Asthma & COPD conference, held in Philadelphia, included topics covering new therapeutic developments in the field of asthma and COPD. This conference report highlights selected presentations on mAb treatments for asthma, including targeting IL-5, IL-13, IL-9 and TNFa, CCR3 inhibitors, histamine H4 receptor inhibition, novel mouse models of COPD and inhaled antisense asthma therapies. Investigational drugs discussed include mepolizumab (GlaxoSmithKline plc), benralizumab (BioWa Inc/Kyowa Hakko Kirin Co Ltd/MedImmune LLC), AMG-317 (Amgen Inc/Takeda Bio Development Center Ltd), TPI-ASM-8 (Pharmaxis Ltd) and AIR-645 (Altair Therapeutics Inc).

The International Society for Eye Research--XIXth Biennial Meeting, held in Montreal, included topics covering new therapeutic developments in the field of eye disease research, including ocular oncology. This conference report highlights selected presentations on uveal melanoma and retinoblastoma.

The formation of anti-drug antibodies represents a risk that should be assessed carefully during biopharmaceutical drug product (DP) development, as such antibodies compromise safety and efficacy and may alter the pharmacokinetic properties of a compound. This feature review discusses immunogenicity issues in biopharmaceutical DP development, with a focus on product quality. Excipient-induced and aggregate-induced immunogenicity are reviewed based on the concepts of 'aggregation-competent' species and 'provocative' aggregates. In addition, the influence of formulation parameters, such as particulates and contaminants appearing in the DP during processing and storage, on aggregate-induced immunogenicity are presented, including the role of fill-and-finish equipments and the effect of interactions with container materials. Furthermore, methods to detect and quantify aggregation and precursor conformational changes in a protein formulation are reviewed, and immunological mechanisms that may lead to aggregate-induced immunogenicity are proposed and discussed.