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H2020Doctoral network2016–2019

ISOTOPICS · ISOTOPIC LABELING FOR DRUG INNOVATION

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2016-01-01 → 2019-12-31
EU contribution
€3,948,844
Participants
13
Scheme
MSCA-ITN-ETN

Lines connect the coordinator with its partners.

Results in brief

ISOTOPIC LABELING FOR DRUG INNOVATION

Presently, less than one drugable compound on ten entering clinical trials effectively reaches the market. This excessive drug attrition rate is mainly due to insufficient preclinical studies of new chemical entities. Drug Design and Development (DDD) might be derisked by the use of isotopic (radio)labeling which enables to tag and trace drug candidates in vivo at an early stage of drug research. However, this task is often difficult and time-consuming due to the scarcity of efficacious late-stage labeling methods and the lack of specialized chemists, familiar with isotopic chemistry but also medicinal chemistry applied in both the academic and industrial sectors. The ISOTOPICS Innovative Training Network, gathering 5 academics and 3 industrial beneficiaries, has therefore defined 3 main objectives: i) To train 15 Early Stage Researchers (ESRs) as the next generation of European chemists with expertise in isotopic labeling and advanced medicinal chemistry through a first-class research training program combined with a highly interactive secondments plan; ii) To develop innovative and general isotopic labeling chemistry and radiochemistry to streamline the synthesis of labeled small-molecule drugs and biologics for therapy but also for diagnosis. The project is limited to hydrogen isotopes (2H, 3H), carbon radio-isotopes (11C, 14C) and fluorine radio-isotope (18F) which are well-admitted for such preclinical/clinical studies by the drug regulation agencies. iii) To work closely with the European pharmaceutical industry to apply the new labeling methods to drugs currently in development. Main Goals of ISOTOPICS Network: High quality science High quality training Joint papers Leverage other grant application Decrease drug attrition and streamline DDD Key achievements: 15 Fellows appointed (ESR) Gender balance (> 53% women) -5 training schools completed according to the training plan. 7 ISOTOPICS International Meetings Completion of secondments (typically 2/ESR including 1 in industry) Awarded: 4 prizes for oral communication (Award for junior synthesis), and 2 prizes for posters, 1 fellow PIs recipient of an ERC-Advanced and 1 FET Open granted in 2019 30 scientific papers published in high impact factor journals (regarding speciality), global mean impact factor = 11.51.

Data: CORDIS, © European Union

Project objective

Excessive attrition rates during clinical trials dramatically impact on Drug Discovery and Development (DDD). Absorption, Distribution, Metabolism and Excretion studies carried out on larger series of drug candidates at an earlier stage of the DDD timeline and evaluation of drug efficacy through better assessment of pharmacokinetic/pharmacodynamic relationships, target engagement and receptor occupancy are critically important approaches for de-risking drug innovation since they facilitate early identification of the candidates that display the best in vivo profile. When successfully implemented, this strategy can accelerate the discovery of new therapeutic solutions to existing and emerging diseases, and enhance European pharmaceutical innovation. For implementation, large sets of isotopically-labeled molecules are required and consequently, a huge revival of labeling techniques is urgently needed. Another crucial issue is the scarcity of expert radiochemists in Europe and the lack of first class training programs in this inter-disciplinary field merging chemistry, radiochemistry and medicinal chemistry. The aims of ISOTOPICS are: i) to train the next generation of European chemists with expertise in isotopic labeling and advanced medicinal chemistry through a first-class taught and research training program combined with a highly interactive secondments plan; ii) to develop innovative and general isotopic labeling chemistry and radiochemistry to streamline the synthesis of labeled small-molecule drugs and biologics; iii) to work closely with the European pharmaceutical industry to apply the new labeling methods to drugs currently in development in order to provide solutions to the most pressing problems in drug innovation. This highly interdisciplinary project is expected to have a profound beneficial impact on drug innovation in Europe by providing novel efficient techniques and new experts in the fields of labeling and medicinal chemistries.

Original text from CORDIS.

Participants

  • COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES · ParisCoordinatorFrance
  • ASTRAZENECA AB · SodertaeljeSweden
  • CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS · ParisFrance
  • INSTN · SaclayFrance
  • KAROLINSKA INSTITUTET · STOCKHOLMSweden
  • LERMIT · Chatenay-MalabryFrance
  • SANOFI-AVENTIS DEUTSCHLAND GMBH · Frankfurt Am MainGermany
  • Société de Chimie Thérapeutique · Chatenay-MalabryFrance
  • THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OxfordUnited Kingdom
  • UCB BIOPHARMA · Bruxelles / BrusselBelgium
  • UCB PHARMA SA · Bruxelles / BrusselBelgium
  • UNIVERSITE DE LIEGE · LIEGEBelgium
  • UNIVERSITE PARIS-SACLAY · Gif-Sur-YvetteFrance

Links

Data: CORDIS, © European Union