Preclinical research is a vital phase of drug discovery and development, designed to identify a lead candidate from several hits; Galileo helps customers design the best strategy to select the lead drug candidate, thus effectively accelerating the research on new medicines and reducing attrition rate. We offer a full range of studies and bioanalytical services:

• Toxicological screening, to select safe candidates for clinical success

• Pharmacology, to predict biological effect of new therapeutic entities

• Pharmacokinetics and metabolism, to evaluate ADME parameters and drug-drug interactions


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


Verifying the efficacy of your lead molecules is of crucial importance prior to investing further on lead optimization. A number of in vitro and in vivo well-established models to study the effects of the drug in different therapeutic applications are available. In vitro systems are often proposed in the early phases of drug discovery, while the in vivo models are used to support the regulatory strategy.

All our studies are tailored on Customer’s requests and novel disease models can be developed to meet specific requirements.

A number of technologies can be offered to predict mechanisms of action at the molecular level and to learn as much as possible from the experimental model about your compound: gene expression analysis, proteomics, histopathology, clinical chemistry, hematology, immunohistochemistry, blotting techniques, fluorescence microscopy.

Even if GLP standards are not required for pharmacodynamic studies, Galileo Research offers “GLP-like” standards, and works according to a global quality strategy.


In vitro test: Cultures of osteoblasts, osteoclasts, synoviocytes and chondrocytes can be used to mimic the disease and assess drug functionality by measuring:
• cytokine release
• collagen synthesis
• hyaluronic acid synthesis
• GAG synthesis
• Enzyme activities
• Bone mineralization
• Bone resorption/formation
• Phenotype
• Gene expression (PCR, qPCR, microarrays)
• Proteome analysis

In vivo models:
• osteoporosis (by ovariectomy, immobilization, GC-induced)
• osteoarthritis (by ACL transaction, MIA injection, DMM)
• rheumatoid arthritis (by collagen injection)
• osteointegration of titanium implants
• fracture healing
Observations: histology, histomorphometry and immunohistochemistry
Blood and urine analyses for the detection of specific markers.
Gene expression and proteomic analysis on biological samples.
Behavioural testing (rotarod, 4-hindlimbs, Von Frey filaments, incapacitance test).

In vitro test:
Neurons can be cultured and submitted to different stress conditions: cumene hydroperoxide-induced oxidative stress, oxygen/glucose deprivation.
The efficacy of the drug can be evaluated by cell viability, LDH assay, ROS inhibition, enzymatic activities.

In vivo models:
Cerebral ischemia (MCAO): we have settled a model of focal cerebral ischemia induced by transient middle cerebral artery occlusion in obese, diabetic and hypertensive rats. This model is much more robust and valid, in comparison with other methods, and is a good predictor of therapeutic efficacy since it has more similarity to the human conditions. A number of analyses can be performed on this model to monitor the evolution of the disease and to evaluate the impact of drug treatment:
• blood pressure
• brain circulation
• animal behaviour
• brain histology
• enzyme activity
• proteomic analysis
• miRNA
• gene expression

Mood disorders:
• Elevated plus-maze
• Black/white box
• Chronic mild stress
• Forced swim
• Open field
• Appetite behaviour

In vitro test:
In vitro cell growth/viability/cytotoxicity

In vivo models:
Human tumor xenografts in SCID and athymic nude mice (subcutaneous, intraperitoneal, orthotopic).

  • Psoriasis (mouse tail para/orthokeratosis)
  • Acnes vulgaris (P. acnes)
  • In vitro simulation of celiac disease in Caco-2 cells
  • In vivo induced celiac disease in NOD mice

In vitro test

C2C12 myoblasts in culture for the study of proliferation, differentiation in myotubes.

In vivo test

  • Experiments on mdx transgenic mice.
  • Mouse model of polymyositis


In support of human clinical trials and marketing authorization approvals, Galileo Research offers a full battery of toxicity studies for the regulatory development of small drugs, as well as biologics and advanced therapies, in compliance with Good Laboratory Practice (GLP), ICH and OECD guidelines.

Toxicity studies have the purpose to determine the toxicological profile of new compounds or to improve the knowledge on existing ones, with the aim of supporting different formulations, new therapeutic indications or administration routes.

ICH and OECD guidelines are used as main reference guidelines.

The development of anticancer drugs is further regulated by dedicated guidelines. Galileo Research can assist the customers in the design of an appropriate program of non-clinical studies to support the development of anticancer pharmaceuticals.

Bacterial Reverse Mutation Test (Ames’ test)
In vitro Mouse Lymphoma Assay in L5178Y
Unscheduled DNA synthesis in vitro
In vitro gene mutations in V79 cells (HPRT)
In Vitro Mammalian Chromosomal Aberration Test
In vivo micronucleous test in mice

Single dose toxicities in rodents, by different administration routes: oral, dermal, intravenous, intramuscular, intra-articular, subcutaneous, intraperitoneal.
Acute oral toxicity by fixed dose method
Acute oral toxicity by up-and-down procedure
Acute oral toxicity by toxic class method
Acute dermal toxicity in rodents

Repeated dose toxicity in rodents by different administration routes: oral, dermal, intravenous, intramuscular, intra-articular, subcutaneous, intraperitoneal.

  • 28-day Toxicity in Rodents, including main study, recovery, toxicokinetic
    5 rats/sex/group, 4 Groups, 7-Day Dosing
  • 90-day Toxicity in Rodents, including main study, recovery, toxicokinetic
    10 rats/sex/group, 4 Groups, 7-Day Dosing
  • 6-month Toxicity in Rodents, including main study, recovery, toxicokinetic

Reproductive Toxicity in Rodents

  •  Embryo-Foetal Development in Rats
  • Reproduction Toxicity in Rats

Immunotoxicity (unintended immunosuppression or enhancement). The ICH guideline recommends non-clinical testing approaches to identify compounds which have the potential to be immunotoxic, and provides a guidance on a weight-of-evidence decision making approach for immunotoxicity testing:

  • Hematology
  • Histopathology of lymphoid organs
  • NK cell activity
  •  T-cell Dependent Antibody Response (Plaque assay)
  • Mixed lymphocyte reaction
  • Antigenicity (induction of humoral response)

“Stand-alone” studies on local tolerance are generally not recommended by the guideline, in order to reduce the number of animals. Thus, local tolerance endpoints should be included in other toxicity studies. Moreover, in vitro methods, internationally validated and accepted by regulatory bodies, and included in OECD test guidelines, may be used as a partial replacement within a tiered testing strategy or as a stand-alone replacement depending on the outcome of the study.

Single dose local tolerance

Repeated dose local tolerance (up to 4 weeks)

  • Dermal (mouse, rat)
  •  Intra-articular (rat)
  • Intramuscular
  • Ocular (rat)
  • Subcutaneous
  • Intravaginal (rat)

Skin sensitization

  • Mouse Local Lymph Node Assay

In vitro skin irritation/corrosion

  • In vitro skin corrosion in reconstructed human epidermis (RHE) test method
  • In vitro skin irritation in reconstructed human epidermis (RHE) test method

In vitro metabolism:

  • Metabolic stability
  • Metabolite profiling
  • CYP450 inhibition
  • CYP450 induction
  • Phase II metabolism: Glutathion conjugation, Glucuronate conjugation
  • Drug-drug interaction
  • Test systems: human and rodent microsomes, human and rodent hepatocytes, S9, human recombinant CYP450

In vivo pharmacokinetic in rodents, with analytical method set up and validation

In vitro absorption through Reconstructed Human Epidermis (RHE), Reconstructed Human Corneal Epithelium (RHCE), Reconstructed Human Vaginal Epithelium (RHVE)

Analytical methods for the determination of the active principles in biological matrixes can be developed and validated, according to ICH.

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