We know that developing a biochemical assay is one of the first steps in launching a successful drug discovery program. While it is common to rely on a single assay technology for the initial screens, using orthogonal assays offer an opportunity to confidently validate hits revealed in the screen and potentially expedite timelines. These complementary assays can inform on compound behavior, potency, and selectivity, providing guidance for which compounds should progress for further evaluation.
When developing multiple assays, these key solutions can help ensure the highest rate of success:
- An expert team that excels in the design and development of biochemical and binding assays to drive drug discovery with rapid data delivery. There are many methodologies available for biochemical and binding assays. Understanding the caveats and limitations and how to apply them will ensure success for each distinct therapeutic target. Independently, opportunities to multiplex or miniaturize the assay can also lead to faster data delivery and minimal reagent costs.
- Orthogonal assay technologies including optical and radioactivity readouts for biochemical and cell-based assays. It is increasingly evident that label-free readouts such as mass spectrometry can eliminate the false positive and negative results due to optical interference. However, many mass spectrometry (MS) readouts force compromising the assay conditions to enable sufficient detection of the analytes of interest. For examples, buffer components such as salts, detergents, carrier proteins, and cell lysates can induce ion suppression and the analytes of interest either must be purified prior to detection using liquid chromatography or diluted through open port probes, or, these components are simply excluded from the reaction mixture. Yet, these conditions may not secure optimal behavior and/or activity of the target. To overcome this limitation, one MS approach utilizes innovative surface chemistry that opens avenues to optimize the assay conditions according to the needs of the target while maintaining a high-throughput readout. Alternatively, utilizing traditional assay formats remain viable options to generate confidence needed in making go / no-go decisions for progressing candidate compounds.
- A high-quality, lead-like small molecule compound library available for screening in any assay format. Small molecule libraries are critical components for any hit finding effort. It is important to consider diversity, purity, and availability of additional material to follow-up initial screening efforts. Evaluating whether certain filters have been applied to remove, for example, pan assay interfering (PAINS) compounds and the purity of the compounds will support higher validation rates and more cost and time effective paths towards a lead candidate. Finally, evaluating larger libraries of compounds not only may increase the likelihood of identifying optimal leads, it also offers opportunities to cover a larger chemical space increasing the intellectual property in an often competitive field.
Download this case study to learn how SAMDI Tech successfully helped a client with limited resources achieve their goal within an accelerated timeline.