Drug Profiling provides metabolism , pharmaceutics , bioanalysis , pharmametrics and toxicology/safety assessment support to the entire Discovery continuum with the aim of reducing late-stage attrition and cycle times, working in close integration with all functions within Siena Biotech.

Metabolism and Pharmaceutics
The integrated Metabolism and Pharmaceutics laboratory is based on a common technology platform with capacity to support both early Discovery assays with higher throughput and later stage activities with higher content assays.

A tiered screening approach is used, whereby high-capacity screens for physicochemical and ADME attributes are deployed in parallel with primary screening. At this page, the assay format is class-centric rather than compound-centric and aims to rank-order compounds.

Assays provide data to allow characterisation of individual compounds and comprise end-points such as intrinsic clearance, drug-drug-interaction potential, multidrug resistance, cytotoxicity and preformulation screens. The Pharmaceutics function also provides analytical services to the candidate selection stage, and oversees subsequent development activities both for API and for clinical dosage forms.

Bioanalysis
Research aimed at CNS implies nanomolar or subnanomolar effective plasma concentrations. Access to state-of-the-art bioanalytical technology permits a pharmacokinetically driven approach in pharmacology and toxicology. Apart from analysis of drug levels in biofluids this laboratory also provides critical support for endogenous biomarker analysis. The laboratory is based around sophisticated LC-MS-MS instrumentation complemented by appropriate automation.

Pharmametrics
Pharmametrics provides prediction and modelling tools for pharmacokinetics, pharmacodynamics and toxicology global and local in silico property prediction (QSPR) methods which, together with tools for prediction of physicochemical properties allow virtual screening of compounds for metabolic properties ( e.g. metabolic stability, BBB penetration, absorption, CYP regioselectivity, protein binding) as well as toxicological properties ( e.g. hERG binding, genotoxicity and mutagenicity). Complemented with tools for in vivo data analysis, a continuum of data analysis tools is available for all phases of the Discovery process.

Toxicology
The Toxicology group is responsible for all aspects of preclinical safety, including screening cascade criteria, early identification of targets, cytotoxicity ranking tests, as well as follow-up of general toxicology studies and assembling, reviewing and upgrading of safety assessments supporting at least clinical Phase Ib studies.

The group has access to advanced in silico - (QSTR) tools to maximize the potential for early prediction of safety issues within the project flow, and will rely on in vitro tools to investigate and position the relevant mechanisms within each disease area.

The group is also accountable for implementation of appropriate diagnostic tools and the generation of comprehensive safety profiles ranging from safety pharmacology and genotoxicity, to later stage evaluations such as reproductive and developmental toxicity and carcinogenicity.