Hit-to-Lead

Parallel chemistry

The modular design of both PEMfinder® and MacroFinder® molecules makes them amenable to highly automated efficient parallel & split mix synthesis both on solid support and in solution. 
Parallel synthesis means that up to several hundred syntheses can be carried out simultaneously by a robot in an unattended way. This parallel approach allows shortening cycle times and making hit-to-lead and lead optimization processes faster and more efficient.

New PEMfinder® and MacroFinder® molecules are produced in significant quantities in a parallel format and purified using customized high throughput normal and reverse phase preparative HPLC. 

In vitro ADMET profiling

A complete understanding of the relationship between in vitro and in vivo results of bio-active molecules is still elusive. Nonetheless, in vitro studies can serve as adequate tests to predict the in vivo properties of a compound. This is done by a number of in vitro assays that allow the prediction of Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) characteristics of such compounds.

In the process of compound optimization, which is a multidimensional, iterative process of design, synthesis and testing, ADMET data support the selection of compounds having the desired characteristics. Additionally, these data can guide the design of downstream in vivo studies. List of in vitro ADMET assays carried out at Polyphor.

Bioanalytical method development

Excellent specificity, consistency, and robustness are key characteristics of state-of-the-art or appropriate ADMET assays in the drug development process.

Therefore, Polyphor has implemented standards and rules for optimal and reliable ADMET assay method development:

  • Using state-of-the-art equipment and techniques
  • Minimizing inter-assay and inter-laboratory variability
  • Straightforward and standardized performance and evaluation
  • Taking into consideration regulatory authority guidelines
  • Stringent quality control settings
  • Robust and consistent data processing, storage, and archiving

Polyphor’s method development progresses through three phases:

  • Set-up
  • Validation
  • Implementation and routine use

All workflows in this process are well documented and archived. They are completely aligned with the above listed standards.

Assay raw data are processed, stored and archived using high end IT-tools. Based on these tools fast retrieval and comparative assessment of results from different compounds can easily be performed.