Non-GLP Exploratory Toxicology
At Sygnature Discovery, our experienced and skilled teams have access to the latest technology that can make a difference to our clients by designing time- and cost-effective strategies for early toxicology assessment of a compound or compound series.
These strategies mitigate risks earlier and before a compound enters pre-clinical development. Importantly the information obtained can be rapidly used to engineer out toxicological liabilities and accelerate the route to the clinic.
Early, exploratory safety assessment usually includes pharmacology studies, general toxicity studies, toxicokinetic and nonclinical pharmacokinetic studies, reproduction toxicity studies, cardiotoxicity and genotoxicity studies and, for drugs that have special cause for concern or are intended for a long duration of use, an assessment of carcinogenic potential.
Early assessment of drug safety risk in pre-clinical models
- Exposure, toxicokinetics and tolerability studies including safety pharmacology/safety margin (MTD, NOAEL).
- Dose range finding studies. Dose-escalation studies or short-duration dose-ranging studies define an MTD in the general toxicity test species.
- Formulation assessment.
- Tissue analysis.
In vitro metabolic and plasma protein binding data for animals and humans and systemic exposure data in the species used for repeated-dose toxicity studies should be evaluated.
Mechanistic toxicology studies
- Histology, evaluate changes in cell morphology, viability and proliferation.
- Haematology and biochemistry.
- mRNA analysis and CYP expression.
- Protein expression analysis.
Drug-Drug Interactions (DDI) risk assessment
Drug-drug interactions (DDI) refer to simultaneously administered drugs that interfere with each other’s absorption, distribution, metabolism, and elimination (ADME).
- CYP450 induction and inhibition.
- UGT induction and inhibition.
- Time-dependent inhibition.
- Transporters (OATPs, OATs, OCTs, MATE).
Proof of concept for drug mechanism of action or efficacy
- Target engagement.
- Safety and efficacy biomarkers.
Our streamlined procedures and targeted reports allow us to offer credible data with operationally efficient services. Working with Sygnature Discovery will enable you to incorporate the industry’s best practices into your drug testing program.