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The hit-to-lead process (lead generation) takes hits from the early screening phases of a drug discovery project to lead compounds. Selecting and refining well-characterized and optimized lead compounds to become drug candidates is an elaborate and iterative process.
Hits must be validated to ensure they bind specifically to the designated target and selected lead series are then developed, usually improving binding potency by several orders of magnitude while maintaining target specificity and favorable pharmacodynamic and pharmacokinetic properties.
We offer effective orthogonal methods for hit validation and prioritization, supporting multiple parameters such as affinity, permeability, solubility, activity, protein binding, cross-reactivity, and off-target effects, and requiring a combination of biochemical, biophysical and functional biological approaches.
Biacore systems provide an orthogonal method that encompasses both a compound counter screen and a selectivity screen in one assay, providing rank orders based on both affinities and risk for causing off-target effects.
Biacore systems are used in biotherapeutic development for detailed characterization of target specificity, selectivity studies, high resolution dissociation rate analysis, as well as for active binding concentration analysis under relevant buffer conditions and temperatures.
High-content analysis provides physiological relevance and predictive toxicity data during early stages of development, including hit identification and lead generation. Deeper insights into how compounds act in the functional context of whole cells lead to more information and confidence in both hit selection and early safety and efficacy.
Surface plasmon resonance (SPR) label-free technology facilitates detailed study of how lead compounds and antibodies bind to drug targets.
High-content analysis (HCA) gives deeper insights into how a drug or compound acts in a functional context providing for more information and confidence in both hit selection and safety and efficacy.
Biomolecular imagers for sensitive and quantitative digital imaging.
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