Phenotypic Screening for Drug Discovery
Phenotypic screening is maneuvering for the identification of molecules with specific biological effects in cell-based assays or animal models. For example, it can include screening large libraries of chemical compounds in automated high-throughput cellular tests that measure the levels of numerous proteins or effects on components such as cell proliferation. Phenotypic Screening has been the stepping stone for the discovery of new drugs before the advent of molecular biology.
A “phenotype” is any noticeable or measurable biochemical or physical property of an individual, bion or complex system: for instance, the heart rate of a zebrafish larva or the diameter of the nerve fibers that originate from a neuron cell in culture. In phenotypic screening, researchers look at the impression of a substance on a complicated system, rather than on an insular segment of a biological pathway. Phenotypic testing can be conducted in cells, for illustration in stem-cell derived human cells, separated tissues or in whole organisms of different complexity. While these are the most processed and precarious of all assays, the benefits of phenotypic screening are that it produces information on the effect of a bioactive compound directly on an excellent disease-relevant condition.
Why use phenotypic screening preferably than other methods?
A target-based process has limitations
Some factors could describe this situation, including excessive importance on a “one protein, one gene, one target, one drug” philosophy that can be removed from the complicated reality of human biology. This simple appearance is compounded by poor understanding of the biology of diseases and their often complex causative mechanisms. The industry needs phenotypic screening to discover low rates of success in drug discovery, expensive late-stage failures in various phases of clinical trials, and impending patent have confronted the financial feasibility of the pharmaceutical industry. The sector is seeking novel ways to identify medicines and products of importance to the economy and the world.
Phenotypic screening is historically successful
Phenotypic testing has been more triumphant at finding “first-in-class” drugs. The method makes only restricted assumptions about the mechanism of operation and none about the target. Phenotypic screening starts with a more complicated position that is closer to the disease mechanism, making it a better platform for translation. The early phase of phenotypic testing requires biology intensive resources, whereas the target-based screening once a target is selected is chemistry and DMPK intense struggle. It is significant to realize this when embarking on a phenotypic memorandum. More time will be needed to generate and validate assays and leads. A thought out series of counter screens will be useful to guarantee the specificity and decrease of toxicity of hits. Note that these are usually conducted later in a targeted approach following some optimization. Opportunities for innovation occur at all these stages.
Resumed awareness of the value of phenotypic screening to drug discovery generates numerous new opportunities to develop drug discovery success and productivity. For all drug discovery proposes to be successful there is a need for validated translational biomarkers and predictive models of disease to guide drug discovery. The more appropriate the system is to physiology the immeasurable it will predict the clinical success. Regrettably, predictive phenotypic assays and relevant biomarkers are not possible for utmost human infections.
One of the hopes for the genetic metamorphosis was to recognize specific genotypes, genes, and targets that could be employed to guide preclinical drug discovery to identify new medicines. This approach has not been as widely successful as hoped. Aligning these efforts to identify translational biomarkers for phenotypic assays should increase the successful discovery of new medicines. Many of the features necessary to successfully execute a phenotypic drug discovery strategy are also relevant to target-based drug discovery, including how to move forward with an incomplete understanding of the disease pathobiology, chemistry, and mechanisms of drug action.