Once our team has identified promising hits through a comprehensive screening campaign, we assess the hit series to evaluate their potential and select the most attractive for optimization. The series undergo comprehensive profiling and preliminary structure-activity relationships (SAR) are investigated. Each series’s physicochemical properties, potency,selectivity and chemical tractability is evaluated to select only the most promising leads for further development.
We design a strong validation funnel in order to prioritize compounds with bona fide activity and confirm this using orthogonal techniques such as biophysics for target based projects, and/or functional/disease relevant cell models.
The decades-long experience of our team enables us to select the best candidates to move forward into lead optimization, and to identify any potential challenges to address during the lead optimization phase. This includes evaluation of chemical alternatives to hits with low metabolic stability, patent space assessments to ensure patentability of a novel chemical entity, and initial DMPK studies to identify areas of improvement.
- High-throughput screening follow-up and clustering;
- Multi-dimensional optimization of drug-like properties;
- Drug feasibility assessment based on patent space, SAR and DMPK criteria;
- Improvement of ADME properties;
- Scaffold hopping;
- Pharmacophore modelling;
- Evaluation of chemical alternatives.