PI: Alberto Bresciani, Vincenzo Summa
INSTITUTE IRBM- Neuroscience
ADDRESS Via Pontina km 30,600, 00071 Pomezia (RM), Italy
IRBM Science Park is a privately owned preclinical drug discovery group operating within the biotech and pharmaceutical sector, created in 2009 as a spin-off of Merck Research Laboratories, Italy. The research team comprises 180 scientists, more than half holding a PhD, and operates on state-of-the-art facilities covering 70,000 m2 research area. The team has an impressive productivity record having delivered more than 25 preclinical candidates over 9 years. One of these is Isentress, a First in Class HIV integrase inhibitor, winner of the Prix Galien USA 2008 as “Best Pharmaceutical Agent”. Other successful stories close to market are Grazoprevir, an HCV protease inhibitor and Niraparid, a PARP inhibitor antitumor agent. The contributions of IRBM to these achievements are documented in more than 800 papers and 100 patents. IRBM has a long-standing experience in European projects, having taken part in two FP7 projects, now concluded, CARESS (FP7 SME2012, coordinator) and AQUALITY (FP7 SME2011, partner). IRBM is currently active partner in two FP7 projects, THINPAD (FP7 collaborative 2013) and THALAMOSS (FP7 collaborative 2012). Within the H2020 framework, IRBM is partner in the MAGIC BULLET project, a Marie Skłodowska-Curie action, started at the beginning of the 2015.
IRBM host a collection of small molecule compounds of approximately 130000 entities sourced either from more than 30 different commercial providers or produced internally. The collection includes FDA/EMA approved drugs as well as compounds that passed a safety assessment in man. All the compounds to be used in the present project will be sourced from IRBM. The QC department at IRBM will be first in charge of the compound quality control by UPLC/MS in order to verify identity and purity. To this aim an automated sampler and spectra analysis are used to increase the throughput. The in vitro and in vivo pharmacology group at IRBM is mainly focused on the delivery of a preclinical candidate for toxicology and safety preclinical evaluation. The main objective is to deliver support to programs both in small molecules and therapeutic peptides.
To this aim multiple capabilities are available onsite amongst which (i) pharmacokinetic (PK) in mice, rats, dogs, monkeys (cannulated animals, automated blood sampling, specialized in peptide and protein PK); (ii) mechanistic PK studies (oral absorption and first pass extraction, involvement of drug transporters in clearance and absorption mechanisms); (iii) mass balance; (iv) automated metabolic stability screening; (v) cytochrome P450 induction and inhibition; (vi) cell permeability and transport; (vii) in vitro blood brain barrier (BBB) permeability; (viii) metabolic reaction phenotyping; (ix) metabolite identification; (x) plasma protein binding, blood/plasma partition; (xi) formulation support; (xii) prediction of human PK.
In silico and in vitro ADME PK studies
porcine brain endothelial cells and rat astrocytes BBB