Hit to lead

Project-proven drug discovery teams composed of highly experienced bioscientists, medicinal chemists and computational chemists that work as one with our clients to move their projects forward towards the next important decision point.

Our cross-functional teams work in a data-driven manner according to established drug discovery principles to develop hit series into drug-like lead molecules through successive rounds of optimisation and exploration.

Important information: Aurelia Bioscience website pages now redirect to Charnwood Molecular following the company’s acquisition. If you have any questions about our bioscience services or specific content you are looking for please contact   info@charnwood-molecular.com

Hit to lead (chemistry)

Before embarking on a hit to lead campaign, it is important to fully characterise and profile several representative examples from each hit series to develop a thorough understanding of their physicochemical properties, as well as any intrinsic liabilities relating to their absorption, distribution, metabolism and excretion (ADME) characteristics.

Selectivity (i.e., off-target activity) is also an important consideration during this profiling process and the activities of representative examples from each hit series should be profiled against homologous targets, as well as common off-targets (e.g., CYPs and hERG).

The combined results of these activities should be used to define the strategy for the hit to lead campaign and inform decision making around the selection of the best hit series to take forward in the process.

Hit to lead (biology)

Using state of the art equipment we provide support for your hit-to-lead project. These include high throughput Western blot, NanoBRET and Nanoluc cell based luminescence and BRET assays, fluorescence (HTRF, AlphaLISA, fluorescence polarization, prompt fluorescence), flow cytometry, high content imaging and SPR (Biacore 8K).

In combination with our chemistry colleagues we can rapidly iterate the design-make-test process. In concert with the primary assay, we build additional selectivity and specificity assays to differentiate off-target from on-target effects.

For human blood studies we have access to a phlebotomist to isolate different cell populations.

Fully integrated approach

The rapid evolution of hit series towards the identification of novel drug-like lead molecules can only occur when all aspects of the design-make-test-analyse (DMTA) cycle are working together in unison to advance our understanding of the opportunities and liabilities associated with a particular hit series.

New compounds within a hit series are designed to ask specific questions in relation to the activity and property profiles of the series in question. The answers to these questions allow us to develop our understanding of any series specific Structure Activity Relationships (SAR) and Structure Property Relationships (SPR), informing subsequent rounds of the iterative DMTU cycle.

Our experienced synthetic chemistry teams work closely with our medicinal chemistry and computational chemistry colleagues throughout this process, using state-of-the-art equipment to design and deliver focused libraries of compounds to our biological screening group to advance of our understanding of the SAR.

Computational chemistry expertise can also be used to support scaffold hopping activities based on our emerging understanding of the SAR and the key (and coincidental) pharmacophoric features of existing hit series. The identification of new scaffolds can be useful in terms of overcoming any intrinsic liabilities associated with a specific hit series or generating novel intellectual property against an established and heavily prosecuted target class.

The co-localisation of our cross-functional drug discovery teams allows for the rapid sharing of data, which means that we can rapidly react to new data and redirect our efforts in a way that improves the efficiency with which we fulfil our criteria for the transition to lead optimisation.

Project-proven relationships

We also make use of a series of project-proven relationships with leading third-party providers, many co-localised, to identify and optimise against specific liabilities, including ADME/Tox and PK liabilities, allowing us to rank emerging hit series for lead optimisation.

With our partners we routinely assess key ADME/Toxicology liabilities to allow us rank each hit series for rapid lead optimisation.

Our track record

Take a look at an example of our work in this area with the following case study:

Download our eBook on developing effective assays:

Our success stories

View all case studies