Our experienced drug discovery teams have an established track record of working in collaboration with our clients to successfully navigate the challenges of the lead optimisation process, delivering high quality candidate molecules against a pre-defined candidate drug target profile.
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The lead optimisation stage sees a small number of compounds, identified in the hit-to-lead stage, tested on a large number of assays to improve biological activity, potency and selectivity whilst reducing potential toxicity.
Further evaluation of the compounds is undertaken to understand how they are absorbed, distributed, metabolised and eliminated during pre-clinical trials.
Application of bio-assays that are more relevant to the assay biology is conducted using a number of different bio-assay readouts including high content, flow cytometry and Western blotting with relevant human cells and samples.
Studies are carried out to identify relevant biomarkers for the disease and/or look at target expression in tissue isolated from in vivo studies.
At the beginning of lead optimisation, we work in collaboration with our clients to clearly define the target candidate profile for their project. An iterative design-make-test cycle is employed to enable multiple parameter optimisation with the aim of delivering a pre-clinical candidate.
Our bioscientists use a screening cascade to first screen against primary assays before moving below the line for information rich assays.
Our chemists have access to Reaxys databases and use their extensive knowledge of synthetic chemistry to design efficient and tractable synthetic routes to prepare compounds for biological and ADME screening in a timely fashion. We employ a combination of traditional and parallel synthetic, analytical and purification equipment and techniques to rapidly prosecute hit series to identify candidates for clinical evaluation.
Working with partners, we identify a suitable Candidate Target Prolife (CTP) consisting of optimal balance of key biological, ADME, Toxicology and physical properties.
All experimental work is written and stored securely in electronic laboratory notebooks and available for subsequent patents and publications as required. Our project leaders communicate regularly with clients to analyse data and ensure rapid progression of the most promising compounds.
Plus, the use of data analytic tools such as Stardrop ensures progression through lead optimisation is seamless and efficient in the time scale specified.
Our track record
Take a look at examples of work we have carried out in this area:
- How we supported Nflection to deliver the first clinical trial of NFX-179 Gel, a topically applied therapy for the mitigation of Cutaneous Neurofibromatosis Type-1
- Elaboration of existing hits to elucidate SAR
- Successful lead optimisation that led to a candidate now in phase 2 trials
Download our eBook on developing effective assays: