Hit qualification

Hit Qualification

The selection of optimal hits holds immense importance in drug discovery, exerting a profound influence on the downstream program success. Our HTS^PLUS package includes a thorough hit qualification aiming to equip our clients with comprehensive insights into their hits supporting their further decision-making process.

By increasing the likelihood of identifying the best-suited hit compound, minimizing time and cost, mitigating the future risk of failure and enhancing the prospects of developing a successful drug candidate, this critical process shapes the trajectory of drug development.

HTS^PLUS - hit qualification
Let your hit take the highway to the lead!

Our hit qualification package offers a comprehensive solution for meticulously evaluating hits identified through High-Throughput Screening (HTS), providing our clients with vital information to make well-informed decisions regarding hit selection and follow-up activities.

Chemical hit qualification

With more than 10 years experience in early-stage drug discovery, and a broad therapeutic area expertise (e.g. inflammation, CNS disorders and oncology), a dedicated team of medicinal chemists will support you in giving value to your hits and in turn de-risk the subsequent drug development process. Our MedChem team will offer expert advice and guidance for hit prioritization, qualification and pharmacophore studies, through the following range of services:

Establish the game plan - sooner is better!

Expanding the chemical space around hits, by using analogs which are commercially available or designed and synthesized ad hoc, to understand emerging principles of the underlying structure-activity relationship, together with determining their basic physico-chemical and ADME properties will provide essential information for hit prioritization.

The contribution by expert medicinal chemists on the hit qualification aims to provide valuable information on the hit compounds, facilitating the selection of the best-suited molecules and thus enhancing the probability of downstream success.

Of particular relevance is the design and synthesis of focused non-commercial analogs, with pinpoint modifications aimed to address specific potential issues.

This, combined with other components of our integrated package, such as ADME and computational studies, will provide a comprehensive knowledge bundle, which will boost the early-stage drug development.

Services include a detailed medicinal chemistry evaluation, addressing:

chemical tractability and resynthesis of hit compounds;
initial novelty and intellectual property check;
acquisition and/or synthesis of relevant and strategic analogs to probe emerging principles of the underlying structure-activity relationship.

Our specialized analytical team offers an extensive suite of assays designed to provide our clients with in-depth understanding of their hits during the crucial early stages of the drug discovery journey. These assays, which focus on ADME-PK, are instrumental in reducing the risk of failure and optimizing the allocation of valuable resources for subsequent drug development stages.

Our ADME-PK assays include:

Our ADME-PK assays go above and beyond standard protocols, as our team of highly skilled scientists excels in the development of customized procedures tailored precisely to your unique project requirements.

Quality control service: advanced purity assessment

We offer our advanced experience on the small molecule quality check, utilizing UPLC, UV and MS techniques to accurately determine the grade of purity of the compounds. The development of our fast and accurate methods ensure that our clients receive precise and comprehensive purity reports for thorough analysis.

Purification, structural elucidation, and chiral resolution: ensuring compound integrity

Recognizing the paramount importance of working with pure and well-characterized compounds in the drug discovery process, our team of highly skilled scientists leverages various techniques, including Mass Spectrometry and advanced Nuclear Magnetic Resonance (NMR), encompassing both 1D and cutting-edge 2D NMR. These methods enable us to accurately determine compound structures, providing clients with a clear understanding of the molecules of their interest.

Furthermore, our services extend to comprehensive chiral resolution solutions, catering to both small and medium-scale requirements. This expertise allows us to address complex racemic mixtures, ensuring that you have enantiomeric pure compounds, a crucial factor in drug development and the advancement of your research objectives.

At the core of our mission, we empower our clients with state-of-the-art computational chemistry techniques for advancing drug discovery. Our expertise lies in the identification and prioritization of promising hits, supporting hit-to-lead optimization strategies, as well as in the development of client-specific databases. More in detail, our comprehensive range of activities includes:

Our goals are achieved through both machine-learning and physics-based tools:

AlphaFold
Chemaxon Instant Jchem
DataWarrior
Gromacs
In-house Python and R pipelines
KNIME
Reinvent
Schrödinger Suite
Virtual High-Throughput Screening

Screening cascade: biological hit qualification

Screening projects include whenever possible project-specific specificity assays for either deselecting compounds likely to interfere with a common assay or readout system, or orthogonal assays probing the same interaction, but with a different assay format, to positively select compounds with activity in both assays.

Following hit identification and with increasing improvement of compound activity, additional aspects like selectivity (within a target class or orthologues relevant for subsequent animal experiments) or cellular downstream activity (when screening in a cell-free, biochemical assay) gain more relevance.

Test or screening cascades will be tailored to the individual project needs. We can support in the design and experimental realization of all subsequent assays required to successfully progress clients’ projects towards and in the subsequent optimization process.