Identifying functional molecules with the potential to be developed into new therapeutics is often the sole aim of phenotypic drug discovery.
However, the approach also provides valuable opportunities to uncover previously unknown, disease-specific drug receptors that can then be exploited through target driven means. Although target deconvolution has a reputation as a major bottleneck in phenotypic drug development, advances allowing for rapid identification of specific receptors for both biologics and small molecules are increasing the pace of phenotypic drug discovery while also providing access to the significant IP generated by the discovery of novel drug targets.
Phenotypic drug discovery has enjoyed a resurgence of interest over recent years with its relative advantages and disadvantages compared to target-based methods being extensively discussed and debated. Traditionally, phenotypic drug discovery focused on the use of small molecule effector libraries to induce a desired phenotype. However, the principles of phenotypic discovery are now widely applied in the field of biologics, with several established and newly-emerging strategies now being employed for antibody based phenotypic discovery. These approaches can range from: evoking an anti-tumour antibody response through immunisation of animals with tumour tissue (as opposed to single antigen immunisation), through to differential panning of normal/disease cells with antibody phage libraries to select molecules that meet disease-relevant functional endpoints....
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