MercachemSyncom has a well-established track record in advancing drug-discovery programs for both large pharma and small biotech organizations. As medicinal chemistry has become one of MercachemSyncom’s fastest growing business units, the company felt it was important to strengthen its ADME and DMPK capabilities. With the integration of Admescope into the MercachemSyncom family, the organization has added that expertise to its portfolio. The in-house presence of all necessary ADME and DMPK assays and expertise guarantees quick turnaround of data and a more efficient design-make-test-analyze medicinal chemistry cycle.
The joint forces of MercachemSyncom and Admescope allow our drug-discovery chemists to focus not only on improving potency, but also on druglike properties. Besides the measurement of physicochemical properties, results from in vitro drug metabolism studies are used to predict hepatic clearance and the extent of first-pass metabolism. Determination of metabolic stability and the ability to identify metabolic soft spots and reactive metabolites early on in a drug-discovery program can be of great value.
In the lead optimization stage of a drug-discovery program, comprehensive in vitro ADME profiling needs to be complimented with animal experiments to provide deeper insights into drug metabolism and pharmacokinetics (DMPK). In an in vivo setting, all physiological factors contribute to the obtained data, enabling a better overall understanding of the compound of interest. Occasionally, animal experiments may reveal ADME issues that were not expected based on earlier in vitro data, and more investigation may be needed to advance the project. In vitro to in vivo extrapolation (IVIVE), combined with physiologically based pharmacokinetic (PBPK) modeling, offers an approach to understand the mechanisms affecting pharmacokinetics. The design of follow-up experiments requires deep expertise and a project-specific focus, and that is another reason why the acquisition and integration of the Admescope team into the MercachemSyncom organization is of such high value.
When a lead compound has been identified, Admescope’s services include the whole spectrum of metabolites in safety testing, starting from in vitro cross-species comparison and metabolite profiling to detecting potential MIST issues. In addition, evaluation of the potential risk for drug–drug interactions using enzyme phenotyping, enzyme inhibition, and induction assays, as well as transporter-mediated drug–drug interaction studies, can form part of the safety assessment.
Admescope has a long history of providing its clients with expert design and focused nonclinical ADME and DMPK studies. In the process, Admescope not only provides data, but also the accompanying context and advice on how to use that information to guide the next steps of the project. Their expertise extends beyond the hit-to-lead and lead optimization stages. After clinical candidate selection, regulatory-compliant DDI studies or transporter DDI assays/MIST analysis can be performed to support an IND application or after a compound has entered the first human studies.
With the merging of MercachemSyncom’s drug design and synthetic expertise with Admescope’s ability to generate comprehensive and tailored, high-quality ADME and DMPK data, our organization is now in an even better position to perform multiparametric optimization. Not only do we have the ability to generate those data in-house with state-of-the art analytical equipment, we also have the required deep expertise to interpret and use these complex data sets. Our ability to integrate these services will undoubtedly facilitate and accelerate the advancement of our customers’ projects.