Phenotypic or target-based drug screening? Combining them is the way to go!
Our most recent webinar explores effective ways to apply the current approach in drug screening to deliver more first-in-class compounds using high content imaging and verified specific antibodies.
The webinar entitled “Combining phenotypic and target-based screening” is now available for you to watch ‘on demand’ on our website.
Back to the future
Up until the 1970s, the early phase of drug discovery relied on phenotypic screening methods. This seemed to be a good approach as the most successful drugs and second medical indications originate from this strategy that is now about to return. So why did drug discovery labs divert from this successful route?
Ever since we started to gain better understanding of the molecular background of diseases it appeared to be more efficient to target the problem directly with target based drug-screening. However, the low success rate in creating first-in-class compounds made labs rethink their strategy.
All for one and one for all
Billions were spent based on the idea that one drug would hit one target or one gene and produce the one most advanced treatment using this straight forward more cost-effective drug development route. No one expected a 90% fail rate at clinical trial Phase 1 and over 50% fail rate at the clinical trial Phase 3 (Nature Reviews Drug Discovery (2011) 10:507-519).
The most common reasons for drug failure at such a late stage of the development process are due to system redundancy and cytotoxicity. Drugs failing at such a late stage use up huge amounts of effort and money!
Backing up the strategy
However, going back to phenotypic screening practices is not the solution for all drug development issues. It is still a challenge to find the target or targets that are being hit by the disease modifying candidate drug molecule and many drug discovery labs prefer to remain focused on target-based screening.
As much as it has become necessary to look at integrated systems during drug development, knowing your target is also an important advancement of our time. Therefore combining the two approaches gives the greatest opportunity to understand the broad mechanism of drug action and be able to discover targets with new therapeutic potential.
How to screen target and phenotype in one go
Our webinar titled “Combining phenotypic and target based screening” also features Cell Signalling Technology (CST) provides information about:
- How high content imaging in combination with specific antibodies can work together to visualise and monitor drug effects on cells – “Systematic Biology Screening”
- How targeted antibodies can be applied to explore the consequences of drug candidates on specific pathways or individual targets
- The effects on cellular processes that can be observed and how (e.g. apoptosis, autophagy, cell cycle and cell migration)
- How to perform high content, whole well analysis of combined assays at high speed using the acumen imager
- The power of activation state-specific antibodies and how to apply them to their full potential to visualize cell-based endpoints (signalling, metabolism, cell death, proliferation etc.) and cellular pathways with no obvious endpoints