Aqueous solubility is an important determinant of the usefulness of a drug candidate that may have a marked impact on the whole process of drug discovery and development.

The partition coefficient is a measure of differential solubility of a compound in a hydrophobic solvent (octanol) and a hydrophilic solvent (water). This value enables compounds to be ranked in terms of hydrophilicity (or hydrophobicity).

One of the keys to understanding how a drug will dissolve in vivo, after oral administration, is to know how soluble it will be in the very different environments of the stomach, small intestine, and colon. Test systems consist in Simulated Gastric Fluid (SGF) and Simulated Intestinal Fluid (SIF), in fed/fasted conditions.

The binding of drug to plasma (and tissue) proteins is a major determinant of drug disposition (distribution). Binding has a very important effect on pharmacodynamics since usually only the unbound drug interacts with its molecular target. Protein binding assay can be done on plasma originating from any animal species. Usually human and rat plasma are tested in order to facilitate comparison between non-clinical and clinical data.

These parameters are very important in defining the pharmacological and toxicological profile of drugs. Metabolic stability is studied on microsomes from different animal species.

Useful to understand degradation to predict efficacy, right timing for PK analysis. Can be performed in plasma from different species, to allow comparison between non-clinical and clinical data.

A test on static or dynamic in vitro model of BBB to predict the passage of drugs in the brain.

Fundamental to understand bioavailability of CNS drugs. This test is done in vivo, on a small number of mice.

A test to predict the oral absorption of drugs. The assay measures drug transport across a Caco-2 cell monolayer bidirectionally, thus predicting whether the molecule undergoes active efflux.

Important to determine the role of P-glycoprotein in the active transport of the compound across Caco-2 cell monolayers.

Reconstructed Human Epidermidis is used as the test system to evaluate transport through the skin.

Gives information on potential drug-drug interactions. CYP1A, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 are the most important proteins; other isoforms are available. Test systems are represented by human hepatocytes, microsomes or recombinant isoforms. The same substrates from rats can also be used.

Glutathion conjugation, Glucuronate conjugation.

In vitro/in vivo models are listed in the section of Pharmacodynamic Assays. We can propose an extensive list of preclinical disease models in the field of cancer, bone and cartilage diseases, skeletal muscle pathologies, CNS disorders, GI diseases and dermatological pathologies.

In order to detect any toxic effect as early as possible in the development process, Galileo Research proposes customised safety testing strategies, that include in vitro and in vivo (rodents) toxicity studies, optimizing costs and timing. The strategies can also include toxicogenomics analysis as a complementary approach to analyze the gene expression profile and identify changes associated with drug-induced toxicities. TGx is not yet a substitute for regulatory toxicity testing, but it can be informative for internal decision-making during preclinical development and can be applied to derisk compound development looking for undesirable mechanistic signatures in appropriate cellular models.
· Single dose toxicity
· Repeated-dose toxicity (14-day)
· Genotoxicity (Ames’ test, Mouse Lymphoma assay)
· In vitro cytotoxicity