Hit Validation

Once a promising drug target has been identified, the goal of the drug discovery phase becomes to search for promising compounds that can interact with the target to produce desired biological effects. Hit compounds are the selected molecules which have the desired activity in compound screening. A wide variety of screening technologies are available including but not limited to high throughput screening (HTS), focused or knowledge-based screening, fragment-based screening, physiological screening, phenotypic screening, secondary screening and virtual screening. The choice of the screening technology depends on the biology of the drug target, compound screening scale, the equipment infrastructure, etc.

High quality of the starting hits makes faster progress with lower attrition rates in drug discovery project. Although most screening identifies many potential compounds, the critical step is to validate the hit. There is a strong need to ensure that the selected hit compounds can actually interact with the target, and that the interaction is specific to the biological processes that need to be modulated. Thus, it is important to develop pharmacologically relevant hit validation assays after hit identification and for the subsequent hit-to-lead selection process. The factors required for assay development include the ability to identify compounds with the desired mechanism of action, the reproducibility of drug discovery procedures, the quality of the standard compounds within predefined limits, and the insensitivity of the compounds to the concentration of solvents used in the assay.

The hit validation process typically consists of a suite of assays to confirm the hit activity and on-target activity. This process aims to eliminate false positives, confirm the activity with the expected target, and to establish the initial ranking of compounds by activity. The assays to confirm the hit activity and on-target activity usually involve determination of synthetic tractability, potential of reactivity and toxicity, assessment of drug-likeness and ligand efficiency, and exploration of structure-activity relationship (SAR).

Creative Biolabs provides powerful risk-based preclinical data verification services for hit validation of drug discovery process to deal with data reproducibility crisis which is a big obstacle for drug research and development and may lead to failure and high risk of investment. Hit validation can also assist our clients' specific objectives of drug discovery and improve the success rate of their projects.

Creative Biolabs' professional scientific team involving biologists, chemists, and pharmacologist will conduct in-depth analysis of the selected hit compounds to confirm the activity. To make sure that the activity is reproducible, hits in the primary assay will be re-tested using the same conditions. Hit compounds confirmed by various validation assays are ranked in order to give the possibility to our clients to move forward to the next phases as soon as possible. Only the confirmed hits can past this stage of drug discovery process in order to help reduce risks of investment and drug development.

Hit Characterization

Creative Biolabs provides hit characterization services from cheminformatics, biophysical characterization to SAR and QSAR models. In-depth characterization of hit compounds is valuable for the lead optimization and ultimately clinical development, and can help avoid drug candidate failure in clinical trials due to their poor synthetic tractability or pharmacological properties.

Counter-Screen

Creative Biolabs provides counter-screen services to eliminate false positives caused by the effect of compounds on the assay technology or format of primary screen as well as compounds with undesirable properties such as cytotoxicity. We provide professional luciferase reporter assays, cytotoxicity assays and cell-based high-content cytotoxicity screening to support our counter-screen services.

Orthogonal Assays

Creative Biolabs provides orthogonal assays following primary screen to distinguish between compounds that generate false positives and those that can genuinely active against the target in order to further eliminate false positives and confirm the activity. We offer a wide range of technical platforms for orthogonal assays to drive forward and speed up your drug discovery process.

Secondary Screening Assays

Creative Biolabs provides secondary screening assays to confirm hits efficacy by a series of functional cellular assays which are vital to ensure that hits generated from high throughput screening campaign are reliably translated into leads. We serve an efficient, flexible and economical secondary screening platform to avoid target-compound binding mistakes from HTS assays.

In addition, Creative Biolabs has a dedicated assay development team that will work closely with you to design customized assays according to your hit identification process. Our service will meet your specific needs fast at extremely competitive prices and fully optimize your pharmaceutical pipeline. If you have some specific questions, please feel free to contact us. We look forward to working with you to help your drug research and development project succeed.