Musumeci D.,University of Naples Federico II |
Roviello G.N.,CNR Institute of Biostructure and Bioimaging |
Montesarchio D.,University of Naples Federico II |
Sapio R.,Bionucleon Srl |
And 3 more authors.
RSC Advances | Year: 2013
We here report the design, synthesis, and biological activity of a kinked hairpin-loop DNA acting at low nM concentrations as a strong inhibitor of HMGB1 (High-Mobility Group Box-1), a nuclear protein with cytokine activity in a number of inflammatory diseases. Lead compound optimization has been realized by inserting different oligo-ethylene glycol spacers at the 5′-end and loop positions of the natural hairpin DNA, in order to improve its enzymatic stability and structuring capability, as well as its overall pharmacokinetic properties. Thermal stability data as well as activity assays proved that the ODN which contained two hexa-ethylene glycol spacers, one at the 5′-end and the other in the loop, was the best candidate to inhibit HMGB1. Plasma stability assays and hydrodynamic volume measurements afforded further encouraging results in view of future in vivo evaluation of the optimized ligand. This journal is © The Royal Society of Chemistry 2013.
Musumeci D.,CNR Institute of Biostructure and Bioimaging |
Bucci E.M.,CNR Institute of Biostructure and Bioimaging |
Roviello G.N.,CNR Institute of Biostructure and Bioimaging |
Sapio R.,Bionucleon Srl |
And 4 more authors.
Molecular BioSystems | Year: 2011
In this work we report the design and synthesis of kinked oligonucleotide duplexes as potential inhibitors of HMGB1, a cytokine which triggers a broad range of immunological effects. We found that the designed ligands can interact with HMGB1, as evidenced by circular dichroism spectroscopy, and are able to block some extracellular effects induced by the protein, such as cellular proliferation and migration, as we demonstrated by in vitro biological assays. After selecting the most stable and active kinked duplex, we synthesized the corresponding PNA/DNA chimeric duplex which resulted to be more resistant to enzymatic degradation, and showed a biological activity comparable to that of the natural duplex. Preliminary in vivo assays in a mouse inflammatory model, showed a significant decrease of the mortality after administration of the PNA/DNA kinked duplex to LPS-treated mice. © The Royal Society of Chemistry 2011.
News Article | December 9, 2016
— Neuroblastoma Pipeline Market Companies Involved in Therapeutics Development are Ability Pharmaceuticals SL, Acetylon Pharmaceuticals Inc, Advanced Accelerator Applications SA, Alissa Pharma, Ampio Pharmaceuticals Inc, APEIRON Biologics AG, AstraZeneca Plc, Bayer AG, Bellicum Pharmaceuticals Inc, Bexion Pharmaceuticals LLC, BioLineRx Ltd, Bionucleon Srl, Biotec Pharmacon ASA, Cancer Prevention Pharmaceuticals, Inc., Cebiotex SL, Celgene Corp, Cielo Therapeutics Inc, Cleveland BioLabs Inc, Codagenix, Inc., CorMedix Inc, Curis Inc, Cyclacel Pharmaceuticals Inc, DEKK-TEC Inc, EnGeneIC Ltd, Errant Gene Therapeutics LLC, F. Hoffmann-La Roche Ltd, GlaxoSmithKline Plc, Green Cross Cell Corp, Ignyta Inc, Incuron, LLC, Juno Therapeutics Inc, Kolltan Pharmaceuticals Inc, Lindis Biotech GmbH, MabVax Therapeutics Holdings Inc, MediaPharma srl, Merck & Co Inc, Merrimack Pharmaceuticals Inc, Morphogenesis Inc, Novartis AG, Novogen Ltd, OGD2 Pharma SAS, Pfizer Inc, Pharmacyclics Inc, Progenics Pharmaceuticals Inc, ProNAi Therapeutics Inc, Recombio SL, Ribomic Inc., Sapience Therapeutics Inc, Sareum Holdings Plc, Shionogi & Co Ltd, Syros Pharmaceuticals Inc and Tiltan Pharma Ltd. Neuroblastoma is the cancer of the nerve tissues and neural crest cells of adrenal glands, neck, chest or spinal cord, occurring predominantly in children. It usually begins in the adrenal glands further spreading to other parts of the body. The predisposing factors involved in neuroblastoma include genetic conditions. Symptoms include lump in abdomen or chest, weakness, bone pain, breathing problems, dark circles around the eyes and difficulty in movement. The condition may be diagnosed by X-ray imaging, CT scan, MRI, biopsy, urine test, etc. It may be controlled by chemotherapy, radiation therapy, stem cell transplants and medication such as monoclonal antibody regimens. This research provides comprehensive information on the therapeutics under development for Neuroblastoma (Oncology), complete with analysis by stage of development, drug target, mechanism of action (MoA), route of administration (RoA) and molecule type. The guide covers the descriptive pharmacological action of the therapeutics, its complete research and development history and latest news and press releases. Inquire more about this research report at http://www.reportsnreports.com/contacts/inquirybeforebuy.aspx?name=774100 The Neuroblastoma (Oncology) pipeline guide also reviews of key players involved in therapeutic development for Neuroblastoma and features dormant and discontinued projects. The guide covers therapeutics under Development by Companies /Universities /Institutes, the molecules developed by Companies in Pre-Registration, Phase III, Phase II, Phase I, IND/CTA Filed, Preclinical and Discovery stages are 1, 1, 15, 15, 1, 43 and 4 respectively. Similarly, the Universities portfolio in Phase II, Phase I, Preclinical and Discovery stages comprises 8, 7, 9 and 4 molecules, respectively. Neuroblastoma (Oncology) pipeline guide helps in identifying and tracking emerging players in the market and their portfolios, enhances decision making capabilities and helps to create effective counter strategies to gain competitive advantage. The guide is built using data and information sourced from Global Markets Directs proprietary databases, company/university websites, clinical trial registries, conferences, SEC filings, investor presentations and featured press releases from company/university sites and industry-specific third party sources. Additionally, various dynamic tracking processes ensure that the most recent developments are captured on a real time basis. Note: Certain content / sections in the pipeline guide may be removed or altered based on the availability and relevance of data. Buy a copy of this research report at http://www.reportsnreports.com/purchase.aspx?name=774100 • The pipeline guide provides a snapshot of the global therapeutic landscape of Neuroblastoma (Oncology). • The pipeline guide reviews pipeline therapeutics for Neuroblastoma (Oncology) by companies and universities/research institutes based on information derived from company and industry-specific sources. • The pipeline guide covers pipeline products based on several stages of development ranging from pre-registration till discovery and undisclosed stages. • The pipeline guide features descriptive drug profiles for the pipeline products which comprise, product description, descriptive licensing and collaboration details, R&D brief, MoA & other developmental activities. • The pipeline guide reviews key companies involved in Neuroblastoma (Oncology) therapeutics and enlists all their major and minor projects. • The pipeline guide evaluates Neuroblastoma (Oncology) therapeutics based on mechanism of action (MoA), drug target, route of administration (RoA) and molecule type. • The pipeline guide encapsulates all the dormant and discontinued pipeline projects. • The pipeline guide reviews latest news related to pipeline therapeutics for Neuroblastoma (Oncology) • Procure strategically important competitor information, analysis, and insights to formulate effective R&D strategies. • Recognize emerging players with potentially strong product portfolio and create effective counter-strategies to gain competitive advantage. • Find and recognize significant and varied types of therapeutics under development for Neuroblastoma (Oncology). • Classify potential new clients or partners in the target demographic. • Develop tactical initiatives by understanding the focus areas of leading companies. • Plan mergers and acquisitions meritoriously by identifying key players and its most promising pipeline therapeutics. • Formulate corrective measures for pipeline projects by understanding Neuroblastoma (Oncology) pipeline depth and focus of Indication therapeutics. • Develop and design in-licensing and out-licensing strategies by identifying prospective partners with the most attractive projects to enhance and expand business potential and scope. • Adjust the therapeutic portfolio by recognizing discontinued projects and understand from the know-how what drove them from pipeline. For more information, please visit http://www.reportsnreports.com/reports/774100-neuroblastoma-pipeline-review-h2-2016.html