Hit Identification with Charles River

Depending on your research goals, the nature of your project and the resources you have available, designing a hit identification campaign which can deliver relevant, high-confidence, and progressable leads can be a complex and nuanced process.

Good decisions and impactful hits at this early stage can influence your research all the way to market, so it’s crucial to make hit finding choices that will meaningfully support your research both in the short and long term. Our experienced hit identification teams specialize in evaluating early-stage programs and working with you to design the best hit ID strategy for successful progression.

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How to Make Successful Hit Finding Choices
In this webinar, learn how the criteria that influence how different hit finding approaches align with your drug discovery ambitions, and the decision-making behind successful Hit ID study selection.
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Creating Your Hit Finding Strategy

Hit identification is the process of identifying and delivering a compound with confirmed activity against a biological target; hit finding typically occurs after target identification and validation, and before hit-to-lead and lead optimization studies. The two main approaches to hit ID are target-based and phenotypic.

With a broad range of methods, technologies and screening libraries, you have a lot of hit identification options open to you. If you’re not sure which methods will best support your short and long term goals, or would like to validate your choices before locking in your assay selection, we can help.

Below is a starting point for determining the core approach you need. Alternatively, get in touch to start an exploratory conversation with our hit finding team.

Molecular Target-Based Screening: Hit Finding for Known Targets

  • I know my target but I don’t know what the function is.
  • I know my target by I don’t know the best method to modulate it. For example:
    • What is the best way to inhibit it?
    • Should I modulate my target at the DNA, RNA, or protein level?
  • I know my target and how I want to alter it, but I don’t know the best way to achieve this.
  • I don’t know if I need more purified protein for successful hit finding.

Phenotypic Screening: Hit Finding for Unknown Targets / Known Phenotypes

  • I have a disease phenotype in mind that I want to modulate and I don’t know the molecular target.
  • I have an unknown mechanism of action in a cell-based system.
  • I have a phenotype that I can modulate but I don’t know the target.  

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Compound Library Quick Guide
Download this guide to obtain a breakdown of our >1.4 million chemical compounds, and learn about our processes for curation, QC, compound management, and screening set design.
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What Technologies Enable Hit ID?

Charles River has a broad suite of hit identification services that can deliver high-quality, validated hit compounds for your drug discovery project. Commission a specific or bespoke assay directly, or work with our team to define and design an approach which will deliver the most impactful hits to support your research goals and drug development plan. 

Learn more about our range of hit ID services here: 

Next Steps

Frequently Asked Questions (FAQs) About Hit Identification

  • What is hit identification (hit ID) in Drug Discovery ?

    The goal of hit identification, also known as hit-finding or hit discovery, is to deliver a molecule with confirmed activity against a biological target. This target molecule is called a “hit” and is the starting point for downstream activities. The hit may also serve as a tool to validate a target.

  • How can in silico screening technologies be used in hit identification?

    In silico screening, also known as virtual screening, uses computational calculations to identify chemical compounds with an enhanced probability of acting on the target of interest with the desired biological effect. Output of a computational screen can be hundreds to a few thousand compounds for subsequent experimental screening and can be used successfully for challenging targets such as GPCRs. As a standalone activity, this computational focus on the compounds that are most likely to be successful results in shorter screen times and reduced costs in hit identification. Computational screening can also be conducted in parallel with HTS and/or fragment campaigns to capture both focused and diversity approaches to hit identification. Learn more here.

  • How long does a hit identification program take and how much will it cost?

    Costs and project duration will vary depending on the drug target and molecular complexity. For planning purposes, Charles River provides guidelines that include prices and estimated duration in months based on projects of typical complexity and duration.

  • What are the different approaches to hit identification screening?

    There are three key approaches to hit finding: phenotypic, target-based and AI-augmented. Phenotypic hit finding is used when the molecular target is not known for a particular disease and allows the generation of hits without understanding the mechanism of action. Target-based hit identification uses a range of experimental methods to identify hits to a known molecular target including HTS, affinity screening and functional screening. AI-Augmented methods use in silico approaches to identify hits.

  • What factors should be considered when deciding whether to use a traditional approach or in silico screening for hit identification?

    The main factor is the presence of a structure for your target. If one is available, in silico methods can be utilized. If there is not a structure this makes in silico methods more challenging and experimental approaches tend to be used, whether phenotypic or target-based assays.

  • Does Charles River offer full-time equivalent or fee-for-service screening services?

    Charles River offers both fee-for-service (FFS) and full-time equivalent (FTE) business models. Projects with a well-defined scope work well using the FFS approach. With projects that require target validation or multiple assay options to be investigated, an FTE approach will be more effective. The FTE model is most agile, empowering the scientific team to make data-driven decisions without contract amendments.