Phase I: Protein to Fragments

Evotec uses its EVOlution™ technology to rapidly identify active fragments crystallized with the protein.

• Development of robust crystallography system for the target protein
• Ultra sensitive high throughput fragment screening technology
• Nanostore™ compound storage technology
• 40,000 fragment library designed and selected by medicinal chemists

Phase II: Fragment to Leads

Evotec employs a number of technologies for the optimization of fragments into lead molecules:

• SAR-by-nearest neighbors, consisting of the in silico selection of analogs of each active fragment from Evotec's database of 3.8 million commercially available compounds
• Fragment growth, which involves the design and synthesis of compounds and focused libraries by identifying additional sites for interaction with the target protein that may be exploited by the addition of functionality to the fragments
• Fragment linking, which is aimed at using dual fragment structures and de novo design to select optimal linkages, with the potential of achieving rapid increases in activity

Evotec's medicinal chemists ensure that even at this early stage compounds are designed to answer key questions and address potential early liabilities including ADMET. Fragment-to-lead projects are conducted in a rigorous and fast manner, involving extensive structure-driven structure-activity-relationship (SAR) exploration to provide robust lead series.

Phase III: Lead Optimization

Our highly skilled and experienced medicinal chemists make use of a hypothesis-driven multi-parameter approach to lead optimization with the aim of improving biochemical potency, efficacy, selectivity and toxicity as well as pharmacokinetics and pharmacodynamics properties to satisfy predefined criteria for a candidate drug to be progressed into development.