In vitro pharmacology and toxicity

Cytotoxicity on primary non-human primates cells (endothelial, epithelial, fibroblast, smooth muscle, hepatic, blood and bone marrow cells).

Primate drug interaction CYP inhibition assays (liver microsomes and primary hepatocytes).

Primate whole blood and PBMC cytokine release assay.

Primate ABC drug transporter assays (primary and recombinant systems).

Information
Assess the potential cytotoxicity of a test compound

Protocol
The test compound is incubated with primate primary endothelial, epithelial, fibroblast, smooth muscle, hepatic, blood and bone marrow cells (cynomolgus, rhesus, marmoset). Alternatively, stable rhesus cell lines can be used (kidney, lymphocyte and lung). Cell viability, metabolism and membrane integrity are assessed using colorimetric or fluorogenic reagents.

Delivery
Cell number, viability, metabolic activity and integrity

Information
Assess the potential immunostimulatory effect of a drug or protein

Protocol
The test article (at different concentrations) is incubated with primate whole blood or peripheral blood mononuclear cells and the time course release of key cytokines is measured by simplex or multiplex immunoassays.

Delivery
Cytokines concentrations, dose-dependence and release kinetics.

Information
Assess how the test compound affects drug metabolism enzymes

Protocol
The test compound (at different concentrations) is incubated with liver microsomes or primary hepatocytes (cynomolgus, rhesus, marmoset). The potential inhibitory effect is assessed using CYP 450 enzyme specific fluorogenic reagents.

Delivery
Simplex or multiplex enzymes inhibition, dose-dependence.

Information
Assess how the test compound affects drug transporters

Protocol
The test compound (at different concentrations) is incubated with primary cells (cynomolgus, rhesus, marmoset). The potential inhibitory effect is assessed using ABC drug transporter specific fluorogenic substrates.

Delivery
Simplex or multiplex transporters inhibition, dose-dependence.

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