Hitting the drug target takes teamwork

Drug discovery programmes can be made or broken by the approaches organisations take in the early stages.

As project viability and investment decisions are often made at drug target identification and validation, it’s imperative to implement robust strategies to make sure well-informed conclusions are drawn and the programme has the best chance of success.

A key part of this process is to have systems that allow integration and the sharing of expertise across different teams, ensuring every team member’s unique abilities can contribute to the success of a project.  

Discover how truly integrated drug discovery approaches can revolutionise your programme with our eBook. 

In this blog, we’ll explore drug target validation, and how adopting an integrated approach enables you to implement robust strategies that ultimately provide strong foundations for your entire drug discovery project.  

What makes a good drug target? 

The types of molecules considered as potential drug targets have broadened in recent years, but there remains a common range of desirable characteristics. To be a real prospect for further study, a biological target must be susceptible to modulation through the binding to a potential therapeutic agent and have a good pharmacological profile. Widely sought-after properties include:

  • A proven function in the pathophysiology of a disease, or in modifying the disease 
  • Expression and activity in disease-relevant cells and signalling pathways 
  • A known and available 3D structure for the assessment of druggability 
  • A level of ‘assayability’ that enables high-throughput screening (HTS), a robust (but not exclusive) method for measuring changes of activity to enable hit-finding and compound evaluation  
  • A promising toxicity profile and the ability to predict potential adverse effects using phenotypic data 
  • The existence of target/disease-specific biomarkers to monitor target engagement and therapeutic efficacy 
  • A favourable intellectual property (IP) status 
  • The likelihood of leading to an improvement over the current standard of care 

A systematic method of drug target validation 

Once a drug target is acquired, the drug’s effect on a target must be shown to provide a therapeutic benefit within an acceptable safety window. This validation step is critical for drug development. When therapeutics in development fail in the clinic, it’s typically due to inadequate target validation.  

To overcome this, the validation phase must include systematic evidence from multiple sources. This approach includes clinical human disease and gene manipulation data, the use of tool compounds biomarkers, biological assays in patient-derived cells, and many other techniques.  

Understanding the biology of the disease is also crucial for target validation. Here, genetic association data and proteomics data, alongside methods to manipulate the genome and proteome (such as CRISPR or genetically modified animal models), are widely used to validate the disease-modifying abilities of drug targets and their targeting compounds. 

All of these facets feed into a scaffold of evidence that supports the confidence in how well the target is linked to the disease and whether modulating it is likely to be efficacious.  

How taking an integrated approach can boost your chances of success in drug discovery

Drug target validation is a significant phase that underpins a project’s viability and investment decisions. It therefore pays to have as wide an input as possible across a range of competencies and to boost the potential of drug discovery projects by creating multidisciplinary team environments and collaborating with external organisations like contract research organisations (CROs).  

As such, creating an environment that enables the true integration of expertise increases the chances of success in drug discovery. Sharing the expertise and experience of different teams, both internal and in partnerships with CROs boosts teamwork efficiency and ensures the most robust experimental designs for further validation.  

This also strengthens confidence in making crucial decisions about a project. There will be times when the evidence indicates that early project termination is the best course of action, or that there is a need to take a different direction to avoid financial wastage down the line.  

The scientific integrity and openness fostered in a truly integrated, multidisciplinary environment also ensures that everyone stays up to date throughout the drug discovery process, keeping abreast of competitor intelligence and operating collaboratively with academic groups in the target space. 

Ultimately, the most powerful approaches to drug target validation harness the shared expertise, deep experience, and practical leanings of a diverse range of professionals. Channelling the experience and expertise of interdisciplinary teams delivers the firepower needed to bring new drugs through the discovery lifecycle quickly and with a greater chance of success.

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