Hoffmann-La Roche | Date: 2016-10-26
The invention is related to compounds, which are GlyT1 inhibitors, for use in the treatment of hematological disorders, in particular for use in the treatment of sickle cell disease and thalassemia, or for the treatment of patients with iron overload syndromes, such as hereditary hemochromatosis.
Hoffmann-La Roche | Date: 2016-10-21
The invention relates to compounds which are mGlu2/3 negative allosteric modulators for use in the treatment of intellectual disabilities. In another aspect, the invention relates to a pharmaceutical composition for use in the treatment of intellectual disabilities comprising a compound according to the invention and a pharmaceutically acceptable carrier.
Hoffmann-La Roche | Date: 2016-10-24
The invention relates to a compound of formula (I) wherein A^(1 )to A^(3 )and R^(1 )to R^(3 )are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.
Hoffmann-La Roche | Date: 2016-04-06
The present invention relates N-(4-tert-Butyl-benzyl)-3-chloro-N-[2-(4-chloro-3-ethyl-phenyl)-ethyl]-2-fluoro-5-trifluoromethyl-benz-amide which is useful in the prevention, treatment, delaying progression and/or reduction of eye diseases, in particular wherein the eye diseases are intraocular neovascular diseases and its method of preventing, retarding and ameliorating eye diseases, in particular intraocular neovascular diseases.
Hebrew University of Jerusalem and Hoffmann-La Roche | Date: 2016-09-08
Uses of a compound of any of Formulas I-VI as a cytotoxic inhibitor of undifferentiated cells are disclosed herein, as well as pharmaceutical compositions comprising a compound of any of Formulas I-VI, and methods for identifying a lead candidate for inhibiting undifferentiated cells. Further disclosed are uses of an SCD-1 inhibitor as a cytotoxic inhibitor of undifferentiated cells.
Hoffmann-La Roche | Date: 2016-10-12
The invention provides novel compounds having the general formula (I) wherein R^(1), Y, A, W, R^(2), m, n, p and q are as described herein, compositions including the compounds and methods of using the compounds.
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-33-2015 | Award Amount: 30.12M | Year: 2016
The vision of EU-ToxRisk is to drive a paradigm shift in toxicology towards an animal-free, mechanism-based integrated approach to chemical safety assessment. The project will unite all relevant disciplines and stakeholders to establish: i) pragmatic, solid read-across procedures incorporating mechanistic and toxicokinetic knowledge; and ii) ab initio hazard and risk assessment strategies of chemicals with little background information. The project will focus on repeated dose systemic toxicity (liver, kidney, lung and nervous system) as well as developmental/reproduction toxicity. Different human tiered test systems are integrated to balance speed, cost and biological complexity. EU-ToxRisk extensively integrates the adverse outcome pathway (AOP)-based toxicity testing concept. Therefore, advanced technologies, including high throughput transcriptomics, RNA interference, and high throughput microscopy, will provide quantitative and mechanistic underpinning of AOPs and key events (KE). The project combines in silico tools and in vitro assays by computational modelling approaches to provide quantitative data on the activation of KE of AOP. This information, together with detailed toxicokinetics data, and in vitro-in vivo extrapolation algorithms forms the basis for improved hazard and risk assessment. The EU-ToxRisk work plan is structured along a broad spectrum of case studies, driven by the cosmetics, (agro)-chemical, pharma industry together with regulators. The approach involves iterative training, testing, optimization and validation phases to establish fit-for-purpose integrated approaches to testing and assessment with key EU-ToxRisk methodologies. The test systems will be combined to a flexible service package for exploitation and continued impact across industry sectors and regulatory application. The proof-of-concept for the new mechanism-based testing strategy will make EU-ToxRisk the flagship in Europe for animal-free chemical safety assessment.
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-03-2015 | Award Amount: 6.00M | Year: 2016
COSYN integrates outstanding European academic and three large Pharma to exploit genomic findings for intellectual disability (ID), autism, and schizophrenia. We capitalise on comorbidity, from clinic to cells and synapses, and have access to large existing samples. We focus on rare genetic variants of strong effect in patients with clinical comorbidity. Our aims are: (1) Understand comorbidity by comparing symptom and syndrome overlap with novel neurobiological criteria; (2) Elucidate mechanisms of comorbidity using neurobiology for the major genomic clue of synaptic dysfunction to unravel the cellular mechanisms of comorbidity; (3) Generate novel neuronal cell models by using advanced technologies to make neurons from carefully selected patients, and use genome editing to create or correct genetic variants. Multiple advanced neuroscience platforms are in place to evaluate an extensive set of molecular and cellular parameters, and to identify alterations in synaptic biology characteristic of ID, autism, and schizophrenia. These cellular models will, with Pharma partners, be up-scaled to provide industry-standard cellular assays for compound screening; (4) Refine diagnostic tools, use novel genomic and cellular features to improve disease classification and discriminate specific patient subtypes; and (5) Case studies in precision medicine: with Pharma partners, identify patients with a genetic change whose consequences can be reproducibly ameliorated in vitro by an approved medication. Recommend to the patient and clinician a double-blinded, N-of-one crossover case study to evaluate the clinical utility of a medication precisely indicated for that person. COSYN is an integrated, state-of-art, bench-to-bedside programme focused on personalised therapeutics. COSYN is a crucial next step in decoding the genetic findings via intensive focus on the clinical and molecular comorbidities of ID, autism, and schizophrenia.
Milletti F.,Hoffmann-La Roche
Drug Discovery Today | Year: 2012
With more than ten new FDA approvals since 2001, peptides are emerging as an important therapeutic alternative to small molecules. However, unlike small molecules, peptides on the market today are limited to extracellular targets. By contrast, cell-penetrating peptides (CPPs) can target intracellular proteins and also carry other cargoes (e.g. other peptides, small molecules or proteins) into the cell, thus offering great potential as future therapeutics. In this review I present a classification scheme for CPPs based on their physical-chemical properties and origin, and I provide a general framework for understanding and discovering new CPPs. © 2012 Elsevier Ltd.
Peters J.-U.,Hoffmann-La Roche
Journal of Medicinal Chemistry | Year: 2013
Polypharmacology describes the activity of compounds at multiple targets. Current research focuses on two aspects of polypharmacology: (1) unintended polypharmacology can lead to adverse effects; (2) polypharmacology across several disease-relevant targets can improve therapeutic efficacy, prevent drug resistance, or reduce therapeutic-target-related adverse effects. This perspective reviews these interconnected aspects of polypharmacology. The first part discusses the relevance of polypharmacology for the safety of drugs, the mitigation of safety risks, and methods to identify polypharmacological compounds early in the drug discovery process. The second part discusses the advantages of polypharmacology in the treatment of multigenic diseases and infections, and opportunities for drug discovery and drug repurposing. This perspective aims to provide a balanced view on polypharmacology, which can compromise the safety of drugs, but can also confer superior efficacy. © 2013 American Chemical Society.