3 Optimal Strategies for HIT Identification in Drug Discovery

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Drug discovery is the first and foremost step towards drug development. However, it is also amongst the toughest and most time-consuming ones. It is a long and arduous process and can take anywhere between four-six years to get completed. Within the process of drug discovery, HIT identification is the first committed step towards a fruitful discovery project.

The fundamental focus of HIT identification is to pick and execute the most suitable hit-finding approach. By applying the perfect approach, the validated hit series would get identified successfully. In other words, through proper HIT identification, the chances of developing drug-like compounds increase significantly.

There are several strategies through which HIT identification can get carried out. Here are the strategies that have yielded the most optimal results in the past several years:

1. Virtual Screening (VS)

Virtual screening refers to a computational technique that is widely used for HIT identification. Under this approach, large libraries of small molecules are scrutinized to identify structures that have significant prospects to bind to a drug target (generally an enzyme or protein receptor).

Primarily, the process of virtual screening gets carried out through two methods- ligand-based technique and structure-based technique.

The point of applying virtual screening in drug discovery is to focus on finding interesting new scaffolds instead of focusing on the total number of hits. It is because a few hits of interesting scaffolds would be more valuable than higher hits of already known scaffolds. Hence, virtual screening is an optimal strategy for HIT identification in drug discovery.

2. High-Throughput Screening (HTS)

High-Throughput Screening is another method of carrying out HIT identification in the process of drug discovery. With the application of liquid handling devices, sensitive detectors and robotics, High-Throughput Screening is able to conduct millions of genetic, chemical, and pharmacological tests.   

Used for the identification of bioactive compounds, the most common targets of High-Throughput Screening are catalytic proteins and enzymes that are responsible for chemical reactions within a cell.

The reason behind why High-Throughput Screening is considered as an optimal strategy for HIT identification is that it is led by functional activity instead of known binding modes. Over the past few decades, the potential of High-Throughput Screening has drastically improved, mostly because of innovations in the field of technology and science.

3. Fragment-Based Screening (FBS)

In the last few years, Fragment-Based Screening has amassed mass popularity in the field of drug discovery. With the ability to present higher HIT rates by screening relatively fewer compounds, it is on the verge of overtaking High-Throughput Screening as the most optimal strategy for HIT identification in drug discovery.

The HIT rates for Fragment-Based Screening are nearly 4-10% higher than other screening techniques. The HIT selection criteria for Fragment-Based Screening generally consists of a ligand efficiency metric.

Moreover, studies have found that under Fragment-Based Screening, the binding efficiency for smaller molecules is more likely to be higher. All of this makes Fragment-Based Screening an optimal strategy for HIT identification.

High-quality HITS need to get identified at an early phase of drug discovery. This is because it gives the project a realistic chance of making it into the final stages of clinical development and forming into a mass-marketed drug.

Final Thoughts


As the pharmaceutical industry is moving into unprecedented times, it has now become more important than ever to adopt optimal strategies for HIT identification in drug discovery. Virtual Screening, High-Throughput Screening, and Fragment-Based Screening are the most popular means of carrying out HIT identification in drug discovery.

Picking any of these screening techniques would help you in optimizing your HIT identification process in drug discovery. For more information: https://www.jubilantbiosys.com/

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