Participants :
KuLeuven, EMC, Institut Pasteur, Riboxx, CISTIM

ADME-Tox and validation in animal models

Type of activity : RTD (Research and technological development including scientific coordination – applicable for collaborative projects and NoEs,).
Lead beneficiary : KULeuven/CD3.
Person-months : 197
Start month : 1
End month : 48

Objectives :

SILVER WP4 will centralize and coordinate (i) ADME- (absorption, distribution, metabolism, and excretion)-tox studies with those compounds that exert the most potent and selective in vitro activity (ii) establish appropriate formulations of these compounds for testing in animal models and (iii) evaluate the potential protective activity in relevant animal models. WP4 aims to

  • Determine ADME-tox profile (Task 4.1) before deciding to study the potential protective effect of novel compounds in an infection model in animals.
  • Establish suitable formulation(s) for administration to animals (Task 4.1).
  • Establish and optimize entero- and flavivirus mouse and/or monkey models for evaluation of novel antiviral strategies (Task 4.2).
  • Assess the efficacy of selected molecules [compounds with potent in vitro antiviral activity and no major liabilities in terms of ADME-tox] in relevant small animal models (mice, hamsters, cotton rats, ferrets) (Task 4.3).
  • Study the protective activity of molecules [with demonstrated outstanding safety and excellent antiviral activity in small animal models (see Task 4.3)] in macaque models (Task 4.4).

Description :
Following verification that in vitro ADME-Tox indicative assays are satisfactory ,lead compounds will be evaluated for toxicity in vivo prior to evaluation of in vivo antiviral activity.

The research leading to these results has received funding from the European Union Seventh Programme (FP7 2007/2013) under grant agreement n°260644-SILVER