Novel Therapeutic Assessment Depends on High-Quality Water
The hit-to-lead and lead optimization stages of novel therapeutic characterization require sensitive, water-dependent experiments
Marnie Willman is Today’s Clinical Lab’s creative services writer/editor. Marnie obtained her BSc from Vancouver Island University and is currently completing her PhD in medical microbiology and infectious diseases at the University of Manitoba. Her doctoral dissertation was focused on the discovery of novel therapeutics for influenza A virus, during which time she also worked as a freelance science writer. Her work has been published in Viruses, iScience, Journal of Virology, Massive Science, The Wire, ASBMB Today, Salon, and MyHealthTeams.
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Once your lab has identified compounds of interest, you can progress to the “hit-to-lead” stage of characterization. A “hit” refers to a compound that has some therapeutic activity. Developing it into a “lead” involves characterizing the compound’s activity at the site, toxicity, potency, and overall effectiveness under different conditions in a high-throughput setup.
The information gained at the hit-to-lead stage is essential for pre-clinical and clinical studies
A compound’s toxicity, potency, and behavior all inform how cellular and animal model testing will proceed. For example, a potential drug’s ability to kill a specific pathogen is irrelevant if it can’t do so without also killing the host. Low potency also presents a challenge; the need to administer a high dose of an expensive drug to achieve the desired effect reduces its feasibility for human treatment.
Making sure that the experimental setup is optimized—and identifying and addressing any potential pitfalls prior to embarking on your project—is vital for success. An often overlooked, but extremely important factor in this work is your water. Is it of high enough quality? Does it contain contaminants that could cause problems for experimental readout? Incorrect results can slow development of a novel therapeutic platform or even stop it in its tracks.
The importance of water in pharmacokinetic drug assessment
A number of assays enable assessment of the efficacy, selectivity, and cytotoxicity of promising drug candidates. The chromatographic, spectrophotometric, and electrochemical techniques used for this work are highly sensitive so that they can detect slight differences in cells and media. If the water used for these techniques is contaminated or of low quality, however, the experiment might pick up the wrong signal, giving you an incorrect answer. This not only confuses the current stage of assessment, but misinforms the next, potentially even halting further analysis.