Target-Based Screening
Learning Objectives
1.Define what Target Based Screening Is
2.Acknowledge when Target Based Screening is Beneficial to Use
3.List an Application of Target Based Screening
Summary
Target-based screening is a high-throughput method that uses recombinant technology and known targets to find a drug that inhibits it (Lage, 2018). Recombinant technology allows gene expression and testing through high-throughput screening (A., Croston). Most of the time in target-based screening what happens is that a certain gene that codes for a protein target is identified and specific compounds for high-affinity binding are found. This is done through targets being analyzed against libraries of thousands of ligands which allows a drug to be produced to inhibit the target compound. After this, then the active compounds can be checked in tissues and whole organisms.
The reason for target-based screening being an example of what we learned this semester, a high-throughput technology, is because one target is being tested through thousands of ligands. By doing this it is an efficient and effective way to find the ligandthat the target best binds to. This is a great example of how a scientist can work backward to identify a solution to a problem.
Target-based screening has been found to be very beneficial! From 1999 to 2013, 70% of the first-in-class drugs that were approved by the FDA were discovered through target-based screening (A., Croston)!
An advantage of target-based screening is that they are more cost-efficient, faster, and easier to run. This makes target-based screening more efficient and effective than other types of screening, such as phenotypic screening. The reason for this is because target-based screening, unlike phenotypic screening, allows for the drug’s molecular mechanism to be known at an earlier rather than later stage. When a molecular mechanism is known, drug discovery can utilize different biotechnologies such as mutational analysis, crystallography, and other processes to understand how a drug interacts with a specific target. The benefit of this is that it allows efficient structure-activity relationship development, biomarker development, and future generations of that drug acting on the target (A., Croston). One disadvantage, however, is that target-based screening can be much more complex than phenotype screening. To be able to do target-based screening you will have to use a number of variables such as protein targets, enzyme targets, cell-signaling receptors, and structural proteins and regulatory factors. If not all of these are present or not fully understood it can be very complex. However, if you do then it is seen to be worth using this method because most first-in-class drugs are derived from this method!
To summarize, target-based screening is used when the molecule that is seen to be causing the disease is already determined and the way in which it works is in question. It is used to find a target for a new drug to combat an untreated disease. Fragment-based screening is an application that utilizes target-based screening.
Fragment-based screening is an application that utilizes target-based screening. Fragment-based screening uses the screening of compounds, which acts as a starting point for drug discovery, against targets (Chilingaryan, Z.). This means that target-based screening can use the knowledge from a fragment-based screening which is better combined with what is for binding purposes to make target screening more efficient!
Questions and Answers
1. How is Target-Based Screening an example of high-throughput technology? Target-based screening is an example of HT technology because one target is being screened against thousands of ligands to see which has the best binding affinity. What makes it HT is the fact that a large screening is occurring and how efficient the process is.
2. Why is Target-Based Screening a good method to use? Target-based screening is a good method to use because it is a good way to solve a problem and process when the process is unknown. It has also been found to be very effective and efficient!
3. Why has Target-Based Screening been seen to be used more than Phenotypic-Based Screening? Target-Based Screening has been seen to be more cost-efficient, effective, and easier to run. They also have produced more first-in-class drugs than phenotypic-based screening.
Audio Recording
References
Lage, O. M., Ramos, M. C., Calisto, R., Almeida, E., Vasconcelos, V., & Vicente, F. (2018, August 14). Current screening methodologies in drug discovery for selected human diseases. Marine drugs. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117650/
A., Croston, G. E., Additional informationFundingThis manuscript has not been funded., & ReferencesSwinney DC. Phenotypic vs. target-based drug discovery forfirst-in-class medicines. Clin Pharmacol Ther. 2013;93(4):299–301. [Crossref]. (n.d.). The utility of target-based discovery. Taylor & Francis. Retrieved March 1, 2022, from https://www.tandfonline.com/doi/full/10.1080/17460441.2017.1308351
Chilingaryan, Z., Yin, Z., & Oakley, A. J. (2012, October 8). Fragment-based screening by Protein Crystallography: Successes and pitfalls. International journal of molecular sciences. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3497300/