NUVISAN Metabolite Discovery

The NUVISAN metabolite discovery platform combines decades of experience in pharmaceuticals and crop protection to solve your requests regarding drug metabolites. We support your fermentation and biotransformation projects and provide your metabolites for pharmacological activity testing, DMPK, and toxicological investigations, and as standards for analytical methods. We identify, screen for, synthesize, and characterize the metabolites of your interest.

Metabolite of MR-Antagonist Finerenone/Kerendia® by hCYP3A4 in E. Coli (Gerisch, M., et al., Drug Metab Dispos, 2018)

For our metabolite screening in the microbiological chemistry group in Berlin, we use wild-type fungi and bacteria strains, various human and bacterial CYPs in cells, and isolated enzymes. A special collection of Streptomyces bacteria allows screening for glucuronides. In addition, we screen various chemical oxidation and glucuronidation methods to identify the most efficient synthetic route to your metabolite of interest.

With our state-of-the-art fermentation platform of 1 L and 2 L Biostat® B-DCU fermenters for optimization purposes and 5 to 100 L steel fermenters for scale-up, we generate drug metabolites in milligram to gram scale with biotransformation. Alternatively, we offer to synthesize your drug metabolite via late-stage diversification, such as chemical oxidations and glucuronidations.

If the chemical structure is known, our discovery chemistry group can produce the drug metabolite by de novo synthesis combining classical drug synthesis with modern chemical methodology as photo- and electrochemistry. Special expertise is contributed by our isotope chemistry and process development groups for the synthesis of labeled drug metabolites.

Our purification platform with state-of-the-art equipment, including normal, reversed phase, and supercritical fluid chromatography, provides difficult and chiral separations for you. A full chiral screening includes up to 200 combinations of conditions in 3–4 days. Challenging separations of chiral compounds are our daily business.

Our analytics platform performs structure elucidation and characterization using NMR, HPLC, HRMS, UPLC-MS, and optical methods (polarimetry, UV, ECD, IR) of the purified drug metabolite, including purity assessments and certifications. Furthermore, our physchem platform offers stability evaluations under various conditions and the measurement and interpretation of physicochemical properties as logD, solubility, and pKa.

Our DMPK group provides metabolite ID and structure elucidation in various biological matrices from in vitro or in vivo samples by LC-HRMS and can confirm the identity of the synthesized metabolite with the desired drug metabolite. In addition, drug metabolite properties, such as metabolic stability, permeability, or protein binding, can be determined for you.

Examples of drug metabolites by NUVISAN metabolite discovery

Metabolite of HIF-PH Inhibitor Molidustat/Musredo® by Streptomyces griseochromogenes (Beck, H., et al., ChemMedChem, 2018)