Transcript CM-0801 New drugs for neglected diseases

COST INFORMATION DAYS
SOFIA, 24-25 OCTOBER
2013 - Hotel Sofia
New Drugs for Neglected Diseases
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Management Commettee Chair:
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Leopold Flohé
Vice chair: Theodora Calogeropoulou
Science officer: Erwan Arzel,
• Administrative officer: Svetlana Voinova
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On July, 30th, 2008, the new Cost-CM0801 Action on "New
Drugs for Neglected Diseases" has officially started by the
signing of the memorandum of understanding by 15
countries.
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Belgium (2)
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Bulgaria (2)
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Finland (2)
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France (2)
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Germany (2)
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Greece (2)
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Israel (1)
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Italy (3)
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Lithuania (1)
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Norway (2)
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Poland (1)
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Portugal (2)
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Slovenia (1)
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Spain (2)
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Sweden (3)
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Switzerland (2)
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United Kingdom (3)
Working groups of the project
Working groups
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Kick-off
meeting of the
management
committee, 28
November,
2008, Brussels,
Belgium.
Working Group 1
(WG1), “Molecular
biology of pathogenic
Trypanosomatidae”
Working Group 2
(WG2),
“Standardisation of
Compound
Documentation”
Working Group 3
(WG3), “Structural
Biology and Medicinal
Chemistry”
Working Group 4
(WG4), “Coordination
and Harmonisation of
Efficacy Evaluation”
Chairs
Helena Castro
Achiel Haemers
Elisabeth
DavioudCharvet
Dr. Vanessa
YARDLEY
New Drugs for Neglected Diseases 2008-2012
PURPOSES:
Development of novel drugs to treat
neglected diseases such as African sleeping
sickness, Chagas disease and Leishmaniasis.
Coordination between related approaches of
molecular genetics, biochemistry, medicinal
chemistry, crystallography and bioinformatics and
complementation with industrial experience.
Identification of the drug targets essential to
the parasites but absent or different in the host,
using the established genomes of the parasites,
since inhibitors thereof hold promise as safe and
efficacious therapeutics.
To validate drug targets as tools in drug
discovery
processes
using
complementary
strategies
New Drugs for Neglected Diseases 2008-2012
STRATEGIES:
• i) high-throughput screening of natural product and other
compound libraries and
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ii) in silico screening of virtual libraries to identify novel
leads;
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iii) chemical synthesis and optimization of identified
leads; and
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iv) structure-based inhibitor design based on established
structures or molecular models. The potential therapeutic
profile of novel compounds active in vitro will be worked
out by techniques of high prognostic value in respect to
drug safety. The most promising compounds will be
tested in established infection models for all the diseases
to choose the most attractive candidates for preclinical
and clinical development. The Action members will cover
all expertises required for the multidisciplinary early drug
discovery phase.
CM0801: New drugs for neglected diseases
Activities
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Kick-off meeting of the
management committee,
28 November, 2008,
Brussels, Belgium.
10th Drug Development
Seminar in conjunction
with the COST Action
CM0801 2009,
Rauischholzhausen
Castle, Marburg,
Germany 18 – 20 March,
2009
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WG1/ WG3 expert
meeting, SouthWest University,
Bulgaria, 29-31
May, 2009
WG2/ WG4 expert
meeting, London,
UK, Sept 21-22,
2009
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Second Annual
Meeting CM0801,
Siena, Italy, from May
28th – 30th, 2010,
Certosa di Pontignano
42nd Microsymposium
‘Glycosomes,
trypanosomatid
metabolism and drug
discovery’ and COST
Expert Meeting ‘Drugs
for Neglected
Diseases’, 28-29
October, 2010
Short technical and scientific
missions
The aim of a Short-Term Scientific Mission (STSM)
is to contribute to the scientific objectives of the
Action.
These Missions (Exchange Visits) are aimed at
strengthening the existing network by allowing
scientists to go to an institution or laboratory in
another COST Country to foster collaboration, to
learn a new technique or to take measurements
using instruments and/or methods not available
in their own institution/laboratory. They are
particularly intended for young scientists.
STSM missions and Bulgarian participations
Tatiana Dzimbova, Training School on "In silico tools for
prioritization of drug targets". Certosa di Pontignano - Siena,
Italy May 16nd – 21th 2011 .
Report “PNA-Synthesis, Properties and Applications”.
Qualification - docking molecular modeling
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Ivan Trenchev, Training School and Workshop VIII EWDD
Eighth European Workshop in Drug Design, Certosa di
Pontignano - Siena, Italy May 22nd – 28th 2011
Poster „Integer programming approaches to HP folding“ N.
Yanev, P. Milanov, I. Trenchev, I. Mirchev –
Qualification & prediction of 3D structure of the chemical
compounds
• ADUN – software NAMD – installed in SWU
• GOLD •
STSM missions and Bulgarian participations
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Tatiana Dzimbova, Training School of the COST Action
CM0801 on “New Drugs for Neglected Diseases” –
Enzyme purification and screening methods in drug
discovery. 28 November – 3 December 2011, Modena,
Italy. – Isolation and purification activity
SOFTWARE PACKAGES INSTALLED AND USED IN SOUTH-WEST
UNIVERSITY IN BLAGOEVGRAD
1. DOCKING AND MOLECULAR MODELING
• MOE - Molecular operating environment; homology
modeling of 3D models of different types of organic
compounds and QSAR
• AVOGADRO (Amedeo Avogadro|) - contemporary
pharmacophore-generating platform for description and
visualization of organic molecules.
• GOLD (Genetic Optimisation for Ligand Docking) docking
• MOLEGRO:
Molecular viewer and Virtual docker
• GAUSSIAN – 3D structure modeling
• AUTODOCK - ligand-target interactions and AUTOGRID
• VMD (Visual Molecular Dynamics)
• EMBOSS (European Molecular Biology Open Software Suite)
2. PREDICTION OF 3D STRUCTURE OF CHEMICAL
COMPOUNDS
ADUN – free molecular simulator for: computer
biophysics, biochemistry, bioinformatics;
distribution - under GNU Public License
NAMD - Not (just) Another Molecular Dynamics
program – for highly parallel computing, suitable
for large molecules;
STSM missions and Bulgarian participations
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Tatiana Dzimbova, 9th Annual Meeting of
Bioinformatics Italian Society (BITS) from May 2-4, 2012.
Catania, Italy poster „Computer modeling of human
delta opioid receptor“, F. Sapundzhi, T. Dzimbova, N.
Pencheva, P. Milanov –
Radoslav Mavrevski, Training School of the COST
Action CM0801 on “New tools for drug design” October
15 – 20 2012, Certosa di Pontignano - Siena, Italy
Fatima Sapundji, Training School of the COST Action
CM0801 on “New tools for drug design” 15 – 20
October 2012, Certosa di Pontignano - Siena, Italy
CM0801: New drugs for neglected diseases
Activities
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In silico tools for
prioritization of drug
targets, May 16-21,
2011, Siena, Italy,
Training School of the
Working Group 1
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Third Annual Meeting •
CM0801. Topic :
Medicinal Chemistry
in Parasitology, 2011.
Modena, Italy, from 57 October 2011
Training School of the
COST Action CM0801 on
“New Drugs for
Neglected Diseases.
Modena, Italy 28
November - 3 December,
2011
WG3 meeting 2012 is
organized by Maurizio
Botta at Certosa di
Pontignano as adjunct
meeting of the IV EWDSy
(European Workshop in
Drug Synthesis;
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4th Annual Meeting
of Action CM0801
"New Drugs for
Neglected
Diseases",
September 19-21,
2012 at Kolymvari,
Crete
COST Action
CM0801 Training
School on “In silico
tools for drug
discovery” , 15-20
October 2012, at
Siena, Italy
OUR OBJECTS:
Trypanothione synthetase-amidase TrS-A
Spermidine analogues as inhibitors of TrS-A
Mu – opioid receptor as target; docking with theoretical
models and with crystallographic forms (Molegro)
-kyotorphins
- endogenous enkephalins
- enkephalin analogues
Delta-opioid receptor – as a target for enkephalin
analogues, substituted with Cys2.
Publications:
T. Dzimbova, R. Mavrevski, N. Pencheva, T. Pajpanova, P.
Milanov (2012) Computer modeling of ligand-receptor
interactions – enkephalin analogues and delta-opioid
receptor. Bulgarian Chemical Communications 44 (3)
242-245. (IF 0.320) ISSN 0324-1130
Tatyana
Dzimbova,
Fatima
Sapundzhi,
Nevena
Pencheva, Peter Milanov (2012) Computer modeling of
human μ-opioid receptor. Peptides 2012: Proceedings
of the 32nd European Peptide Symposium, George
Kokotos,
Violetta
Constantinou-Kokotou,
John
Matsoukas (Editors), 232-233. ISBN 978-960-466-121-3
Tatyana
Dzimbova,
Fatima
Sapundzhi,
Nevena
Pencheva, Peter Milanov (2013) Computer Modeling of
Human Delta Opioid Receptor. Int. J. Bioautomation 17
(1) 5-16 ISSN 1314-2321 (on-line)
Thank you