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Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2011.2.1.1-1 | Award Amount: 39.64M | Year: 2011

In response to the call for a high impact initiative on the human epigenome, the BLUEPRINT Consortium has been formed with the aim of generating at least 100 reference epigenomes and studying them to advance and exploit knowledge of the underlying biological processes and mechanisms in health and disease. BLUEPRINT will focus on distinct types of haematopoietic cells from healthy individuals and on their malignant leukaemic counterparts. Reference epigenomes will be generated by state-of-the-art technologies from highly purified cells for a comprehensive set of epigenetic marks in accordance with quality standards set by IHEC. This resource-generating activity will be conducted at dedicated centres to be complemented by confederated hypothesis-driven research into blood-based diseases, including common leukaemias and autoimmune disease (T1D), by epigenetic targets and compound identification, and by discovery and validation of epigenetic markers for diagnostic use. By focussing on 100 samples of known genetic variation BLUEPRINT will complete an epigenome-wide association study, maximizing the biomedical relevance of the reference epigenomes. Key to the success of BLUEPRINT will be the integration with other data sources (i.e. ICGC, 1000 genomes and ENCODE), comprehensive bioinformatic analysis, and user-friendly dissemination to the wider scientific community. The involvement of innovative companies will energize epigenomic research in the private sector by creating new targets for compounds and the development of smart technologies for better diagnostic tests. BLUEPRINT will outreach through a network of associated members and form critical alliances with leading networks in genomics and epigenomics within Europe and worldwide. Through its interdisciplinarity and scientific excellence combined with its strong commitment to networking, training and communication BLUEPRINT strives to become the cornerstone of the EU contribution to IHEC.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.3.2-2 | Award Amount: 8.47M | Year: 2011

Early stage Drug Discovery efforts over the last 5 years have resulted in the identification of a number of promising lead compounds in the fight against TB. These leads need to be further progressed and optimised into candidates for pre-clinical development through the Drug Development progression cascade. Three compound families are of particular interest: 1) InhA Inhibitors, 2) New potent whole cell anti-tubercular compounds with unknown mode of action and 3) new Beta-lactam/Beta-lactamase combinations for TB. A preclinical package is already in place for some of them, but further work is necessary for others in order to justify the progression of a single anti-tubercular family to the more resource intensive stages of preclinical and clinical development. The project will encompass the parallel progression of the three compound families through: A) Lead Optimization Chemistry efforts and MoA studies (Genetic and Proteomic) for whole cell inhibitors, B) In vitro and in vivo evaluation of a new orally bioavailable Beta-lactam alone or in combination with a Beta-lactamase inhibitor to evaluate the sterilising potential of the new drug/s and C) the optimization of an InhA inhibitor for later preclinical development. These efforts will yield candidate molecules for new information rich in vitro assays of antimycobacterial activity (artificial granuloma, activity against slow/non growing cells and activity against clinical isolates) as well as for in vivo safety and efficacy evaluation in different animal models of infection (acute and/or chronic). At this stage a single compound family will be prioritized. Further studies will be performed assessing the potential for shortening treatment in stand alone therapy as well as in combination regimens both in vitro and in vivo. Finally a Clinical Development plan will be put in place for the selected candidate molecule.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.4.1-2 | Award Amount: 3.92M | Year: 2012

Multiple Myeloma (MM) is a currently incurable rare malignant plasma cell disease, which invariably relapses despite therapy. The objective of OVER-MYR is to understand the causes of drug resistance and relapse, develop novel strategies to overcome these, provide proof of principal for phase I/II trial, and thus impact on MM-patients survival.Currently-used drugs target both MM cells (MMC) and cells of the bone marrow (BM) microenvironment or niche that are critical for supporting MMC survival, proliferation and growth. Since patients repeatedly relapse after such treatments, the following mechanisms of relapse are considered and need to be investigated: i) drugs have spared specific subclones or subpopulations of MMC ii) drugs induce alterations in cells of the niche that promote drug-resistance. OVER-MYR integrates a network of outstanding researchers from 6 EU countries with internationally recognized experience in clinics and human and animal models of MM, who will jointly: WP1: Study the molecular alterations in primary MM and environment cells in samples obtained from a large number of patients at treatment inclusion and relapse, using high throughput techniques. WP2: Implement in vitro and in vivo models of drug resistance to evaluate molecular and cellular mechanisms and compare their characteristics with drug resistant cells isolated from patients. Combined results of WP1 and WP2 will permit the identification of 10 prominent (altered) candidate genes involved in MM relapse. Changes in drug resistance, cell survival and proliferation will be assessed in WP2 by modulating the expression of the selected genes. WP3: Determine how cells from the niche alter their functions in the presence of drugs, and how drug-altered cells impact on MM cells during therapy. WP4: Screen chemical libraries for drugs active on generated sensitive cell lines, develop innovative inhibitors and provide proof of principle for a phase I/II trial


The present invention relates to methods for the characterization of enzymes or of enzyme-compound complexes, wherein the enzyme is obtained from a protein preparation with the help of at least one broad spectrum ligand immobilized on a solid support and wherein the enzyme is characterized by mass spectrometry. These methods are useful for the screening of non-immobilized compound libraries, selectivity profiling of lead compounds and mechanism of action studies in living cells.


The present invention relates to methods for the characterization of enzymes or of enzyme-compound complexes, wherein the enzyme is obtained from a protein preparation with the help of at least one broad spectrum ligand immobilized on a solid support and wherein the enzyme is characterized by mass spectrometry. These methods are useful for the screening of non-immobilized compound libraries, selectivity profiling of lead compounds and mechanism of action studies in living cells.


The present invention relates to immobilization products comprising compounds of formula (I) and preparations thereof as well as methods and uses for the identification of histone demethylase interacting compounds or for the purification or identification of histone demethylase proteins.


Patent
CellZome | Date: 2016-03-03

The present invention relates to compounds of formula (I) wherein R, R^(1), X^(1 )to X^(5 )have the meaning as cited in the description and the claims. Said compounds are useful as TYK2 inhibitors for the treatment or prophylaxis of immunological, inflammatory, autoimmune, allergic disorders, and immunologically-mediated diseases. The invention also relates to pharmaceutical compositions including said compounds as well as their use as medicaments.


Patent
CellZome | Date: 2013-05-23

The present invention relates to compounds of formula (I) wherein R, R^(1), X^(1 )to X^(5 )have the meaning as cited in the description and the claims. Said compounds are useful as TYK2 inhibitors for the treatment or prophylaxis of immunological, inflammatory, autoimmune, allergic disorders, and immunologically-mediated diseases. The invention also relates to pharmaceutical compositions including said compounds as well as their use as medicaments.


The present invention is concerned with substituted bicyclic heterocyclic compounds of Formula (I) wherein Het^(1), Het^(2), A^(1), A^(2), A^(3 )and A^(4 )have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.


The present invention is concerned with novel substituted 3,4-dihydro-2H-pyrido[1,2-a]pyrazine-1,6-dione derivatives of Formula (I) wherein R^(1), R^(2), R^(3), R^(4), R^(5), Z and X have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

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