Hit Picking vs. Hit Selection: What’s the Difference?

In drug discovery, particularly within antibody development, the terms “hit picking” and “hit selection” are often used interchangeably. These processes, while related, represent distinct stages within the broader workflow of identifying candidates with potential therapeutic value. Understanding the nuances between hit picking vs. hit selection is crucial for effectively organizing your discovery pipeline and ensuring that the most promising candidates are advanced for further refinement and characterization.

Contents: Hit Picking | Hit Selection | The Differences

Hit Picking: The Initial Screening

Hit picking is the process of identifying and isolating potential hits from a large pool of screened compounds or antibodies. These hits are typically identified based on their ability to bind to a target or exhibit a desired biological activity in high-throughput screening (HTS) assays.

Key Characteristics of Hit Picking:

1. High-Throughput Nature: Hit picking is performed using automated systems that can screen thousands to millions of compounds or antibody variants rapidly.
2. Initial Identification: At this stage, hits are identified based on primary screening criteria, such as binding affinity or preliminary activity against a target.
3. Broad Selection: The goal is to capture a wide range of potential hits to ensure that promising candidates are not overlooked.

Example Hit Picking Workflow:

1. Library Screening: A large library of compounds or antibodies is screened against a target using HTS assays.
2. Data Analysis: Automated systems analyze the results, identifying compounds or antibodies that exhibit activity above a predefined threshold.
3. Hit List Creation: A list of initial hits is generated, consisting of candidates that met the screening criteria.

 

Hit Selection: Refining the Candidates

Hit selection is the subsequent process of validating and prioritizing the hits identified during hit picking. This involves more detailed and rigorous evaluation via assays and analyses to determine the most promising candidates for further development.

Key Characteristics of Hit Selection:

1. Detailed Evaluation: Hits chosen during hit picking undergo secondary and tertiary assays to confirm their activity, specificity, and potential therapeutic relevance.
2. Data Integration: Comprehensive data, including structure-activity relationships (SAR), pharmacokinetics, and toxicity profiles, are integrated to assess each hit.
3. Prioritization: Hits are ranked and prioritized based on their overall potential, with the most promising candidates selected for lead optimization.

Example Hit Selection Workflow:

1. Secondary Screening: Hits from the initial screening are subjected to more specific and detailed assays to confirm their activity.
2. Tertiary Assays: Further assays, including functional assays, binding kinetics, and in vitro toxicity studies, are conducted.
3. Data Integration and Analysis: Data from various assays are compiled and analyzed to understand the potential and limitations of each hit.
4. Hit Prioritization: Hits are ranked based on a combination of activity, specificity, and drug-like properties, with the top candidates selected for further development.

 

Key Differences Between Hit Picking vs. Hit Selection

Hit picking and hit selection are integral, yet distinct, stages within the drug discovery process. While hit picking involves the initial, broad identification of potential hits, hit selection is a more refined process aimed at validating and prioritizing these hits for further development. 

1. Stage in Workflow: Hit picking occurs at an early stage in the workflow, where the focus is on the initial identification of potential hits. In contrast, hit selection takes place at a later stage, concentrating on the validation and prioritization of these identified hits.
2. Scope of Screening: Hit picking involves a broad and high-throughput approach, aiming to identify a wide range of potential hits from a large pool. On the other hand, hit selection is more focused and detailed, with the goal of refining and prioritizing hits based on comprehensive data.
3. Evaluation Criteria: The evaluation criteria for hit picking are based on primary screening results, often limited to initial activity or binding. Conversely, hit selection involves a holistic evaluation that includes secondary and tertiary assay results, as well as additional data such as pharmacokinetics and toxicity.

 

See What Biologics LIMS Can Do For Your Lab

Biologics LIMS provides an integrated suite of tools that accelerate antibody discovery workflows including screening, hit selection/picking and characterization. The software centralizes data management and connects samples, plates, assays, biological entities, and analyses together for streamlined operations and faster decision-making. Book a demo or take a tour to see it in action.