Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Accelerating Drug Discovery Efforts for Trypanosomatidic Infections Using an Integrated Transnational Academic Drug Discovery Platform
Δημιουργός/Συγγραφέας:	Moraes C.B. Witt G. Kuzikov M. Ellinger B. [EL] Καλογεροπούλου, Θεοδώρα[EN] Calogeropoulou, Theodora [EL] Προύσης, Κυριάκος[EN] Prousis, Kyriakos Mangani S. Di Pisa F. Landi G. Iacono L.D. Pozzi C. Freitas-Junior L.H. dos Santos Pascoalino B. Bertolacini C.P. Behrens B. Keminer O. Leu J. Wolf M. Reinshagen J. Cordeiro-da-Silva A. Santarem N. Venturelli A. Wrigley S. Karunakaran D. Kebede B. Pöhner I. Müller W. Panecka-Hofman J. Wade R.C. Fenske M. Clos J. Alunda J.M. Corral M.J. Uliassi E. Bolognesi M.L. Linciano P. Quotadamo A. Ferrari S. Santucci M. Borsari C. Costi M.P. Gul S.
Εκδότης:	SAGE Publications Inc.
Ημερομηνία:	2019
Γλώσσα:	Αγγλικά
ISSN:	2472-5552
DOI:	10.1177/2472555218823171
Άλλο:	PubMed ID: 30784368
Περίληψη:	According to the World Health Organization, more than 1 billion people are at risk of or are affected by neglected tropical diseases. Examples of such diseases include trypanosomiasis, which causes sleeping sickness; leishmaniasis; and Chagas disease, all of which are prevalent in Africa, South America, and India. Our aim within the New Medicines for Trypanosomatidic Infections project was to use (1) synthetic and natural product libraries, (2) screening, and (3) a preclinical absorption, distribution, metabolism, and excretion–toxicity (ADME-Tox) profiling platform to identify compounds that can enter the trypanosomatidic drug discovery value chain. The synthetic compound libraries originated from multiple scaffolds with known antiparasitic activity and natural products from the Hypha Discovery MycoDiverse natural products library. Our focus was first to employ target-based screening to identify inhibitors of the protozoan Trypanosoma brucei pteridine reductase 1 (TbPTR1) and second to use a Trypanosoma brucei phenotypic assay that made use of the T. brucei brucei parasite to identify compounds that inhibited cell growth and caused death. Some of the compounds underwent structure-activity relationship expansion and, when appropriate, were evaluated in a preclinical ADME-Tox assay panel. This preclinical platform has led to the identification of lead-like compounds as well as validated hits in the trypanosomatidic drug discovery value chain.
Τίτλος πηγής δημοσίευσης:	SLAS Discovery
Τόμος/Κεφάλαιο:	24
Τεύχος:	3
Σελίδες:	346-361
Θεματική Κατηγορία:	[EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry
Λέξεις-Κλειδιά:	anti-infective drugs cell-based assays compound repositories enzyme assays or enzyme kinetics liquid handling
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2019 Society for Laboratory Automation and Screening.
Όροι και προϋποθέσεις δικαιωμάτων:	All Open Access, Hybrid Gold, Green
Σημειώσεις:	Seventh Framework Programme, FP7: 603240; FP7 Health, HEALTH; Seventh Framework Programme, FP7; Klaus Tschira Stiftung, KTS. This project has received funding from the European Union’s Seventh Framework Programme for research, technological development, and demonstration under grant agreement No. 603240 (NMTrypI, New Medicines for Trypanosomatidic Infections). The Authors acknowledge the collaboration of the COST ACTION 1307 for the positive and stimulating scientific environment that contributed to generating the idea and disseminating our drug discovery work in a unified high impact manuscript. I.P., W.M., J.P.-H. and R.C.W. gratefully acknowledge the support of the Klaus Tschira Foundation. C.B. and A.Q. gratefully acknowledge the School of doctorate of CME (Clinical and Experimental Medicine) at the University of Modena for favouring their PhD student research work. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project has received funding from the European Union’s Seventh Framework Programme for research, technological development, and demonstration under grant agreement No. 603240 (NMTrypI, New Medicines for Trypanosomatidic Infections).
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο