Lead optimization is a complex, non-linear process. During this stage of drug discovery, the chemical structure of a confirmed hit is refined to improve its drug characteristics with the goal of producing a preclinical drug candidate.
Typically, confirmed hits are evaluated in secondary assays, and a set of related compounds, called analogs, are synthesized and screened. The testing of analog series results in quantitative information that correlates changes in chemical structure to biological and pharmacological data to establish structure-activity relationships (SARs).
Today, lead optimization often involves a series of standard assays to evaluate toxicity, including P450 inhibition, cytotoxicity assays, and hERG testing. Toxicity in these relatively simple in vitro assays flags hits or leads that could have potential safety concerns.
Another characteristic that lead optimization often evaluates is formulation. Formulation and delivery are closely linked. For example, a drug intended to be delivered via intramuscular injection might call for a different formulation than would one intended for oral delivery. Formulation problems and solutions feed back into the iterative lead optimization cycle.
Molecular Devices offers a range of products that are particularly well suited for lead optimization studies.
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