We aid your search for chemical matter for your target with our integrated target-to-lead pipeline. We offer assay development for high-throughput screening of a 3-million-compound library, fragment screening, and virtual screening. Hit compounds are broadly characterized in biochemical and cellular assays; their binding modes are interrogated by biophysical, MS-based, and structural biology methods. Our medicinal chemists have decades of big pharma expertise to rapidly advance hit chemistries into viable lead structures that align with your project needs.

Entry Screens: High-Throughput, Fragment, and Virtual Screening

The primary screening campaign occupies a key position in the preclinical drug discovery process. High-throughput screening (HTS) is used to identify molecules with suitable target-specific properties en route to developing a promising drug. In our fully automated HTS laboratories, we offer miniaturized, cost-effective biochemical, cellular, and phenotypic assays for hit-finding campaigns. Our equipment enables both microplate-intensive screening of complex, million-member libraries and focused screening of smaller sub-libraries, such as those tuned to target structural properties.

We offer fragment screening as a complementary hit-finding approach, if suitable for your target. High-throughput crystallography is combined with other biophysical methods to identify initial binders using internal NUVISAN fragment libraries. Our medicinal chemists subsequently apply fragment growing, merging, or linking approaches as they advance your initial binders into attractive lead structures, while also improving potency and selectivity.

Virtual screening campaigns offer a cost-effective alternative to conventional hit-finding methods. Our Digital Life Science experts routinely conduct screens against client targets using our internal proprietary chemical database (Life Science Database), as well as external on-the-shelf and make-on-demand libraries. Cutting-edge digital technologies are used to quickly identify lead structures with favorable predicted ADMET properties.

The scientific question at hand determines the screening approach best suited to your project!

Secondary Screening: From Reporter Assays to High-Content Assays

Our experienced team of scientists designs and generates customized cell model reflecting relevant disease processes for deconvolution of your screening hits. Tailored plate reader methodologies can be applied, such as for a broad range of reporter assays. Using our state-of-the-art robotic high-content imaging platform, cellular phenotypes can be measured that confirm hit compound effects in specific signaling cascades or other biochemical pathways.

Hit Selection and Characterization

To efficiently drive your project forward, a multidisciplinary team of experienced scientists analyzes your screening hit lists. Expert intuition and digital filtering methods are used to select hits for advancement. To provide you a comprehensive overview of hit cluster properties, various phys-chem properties (e.g., solubility, polarity) are interrogated. The binding mode of selected derivatives is analyzed with a combination of biophysical, MS-based, and structural biology methods (e.g., NMR, X-ray crystallography, or cryo-EM). This valuable information aids structure–activity relationships (SAR) understanding and supports the hit optimization process. Finally, characterization of ADME properties for the selected hit compounds is essential to identify suitable lead structures.

Hit-to-Lead Chemistry

We have a long-standing expertise in the hit selection process of assessment, modification, and rapid expansion of different hit clusters into lead structures fitting your compound profile. Based on the hit profile and your target product profile, we define a project-specific screening tree that includes all relevant assays for the identified liabilities. Working together with our digital scientists, we take advantage of computer-aided approaches during design cycles. We apply state-of-the-art synthetic methodologies (e.g., photochemistry, electrochemistry, late-stage diversification), as well as microbiological chemistry, to quickly synthesize target compounds-of-interest, and we have expertise in modalities beyond small molecules, including PROTACs, antibody–drug conjugates, and peptides.

Our target-to-lead solutions cover the following: