Pharmacelsus GmbH
Science Park 2
66123 Saarbrücken
Germany
Discovery Lead Optimisation Services
As discovery lead optimisation is a serious bottleneck in drug discovery, Pharmacelsus offers a broad range of beneficial tools for the acceleration of a hit to lead or a discovery lead optimisation process.
Beside the characterisation regarding their physicochemical parameters, a variety of research services in vitro can be conducted to improve the ADMET profile of a lead:
Absorption studies are performed on artificial membranes either for the prediction of intestinal absorption (PAMPA) or CNS penetration across the blood brain barrier (BBB). Our Caco2 method represents a sophisticated cellular model for intestinal uptake, allowing studies on the bi-directional transport of drugs across the small intestine and the detection of P-glycoprotein efflux.
For in vitro studies on metabolism, Pharmacelsus applies several validated models including primary hepatocytes, liver microsomes or cytosol of preclinically relevant species for investigations on metabolic stability, an important consideration in determining a compound’s potential for human use. We monitor the loss of parent compound as well as the formation of metabolites for the prediction of bioavailability, clearance and half-life, and identify the nature of metabolites applying LC-MS/MS, H-D and online-H-D exchange techniques. Specific CYP profiling and CYP inhibition screening is performed using Supersomes® (BD Biosciences), microsomal preparations or cryopreserved hepatocytes.
The degree of binding of a compound to plasma or serum proteins can provide important information about its efficacy and its potential for drug-drug interactions. Pharmacelsus determines the plasma protein binding (PPB) for various species by ultrafiltration or ultracentrifugation methods.
To determine the cytotoxic potential of a compound, its effects on different types of cells including rat or human hepatocytes as well as tumour or fibroblast cell lines, tailored on our clients demands, is evaluated. Our in vitro cytotoxicity assays are based on common viability staining methods (MTT, XTT) or oxygen uptake of the cells via oxygen sensor-plates.
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