Hit generation  

A key asset for our hit-finding activities is our exclusive 90.000 compound chemical library Welabrary. This collection is based on diverse lead-like properties and structural novelty and constitutes an excellent starting point for hit identification.  

Other approaches may include literature-to-hit or de novo design based on the in silico available models and benefiting from a close interaction of the Medicinal Chemists with Computational Chemistry. 

We have significant expertise in validating and prioritizing HTS hits, taking into account principles of lead-likeness, synthetic feasibility, IP, and ADME properties. A rapid hit expansion often provides interesting starting points for Hit to lead programs. In-house proprietary tools for easy visualization of structure–activity and structure–property relationships of each chemical series allow fast iteration and project progression. 

Hit to lead 

The correct choice of the best hits to take forward is critical as it will influence the entire project downstream. Our experienced Medchem teams evaluate hits coming from internal Hit generation programs or from any other external source, including client collections or available literature. 

The initial hit evaluation relies on the careful study of available data regarding: 

• compound stability 
• synthetic routes 
• appropriate molecular descriptors, calculated using our Computational Chemistry platform 
• ADME properties, obtained through our ADME/Tox profiling platform
• initial assessment of novelty and inventive step to achieve Intellectual Property protection

The objective of this preliminary hit evaluation is  to efficiently map structure-activity and structure-property relationships and help evaluate which are the most promising hit classes to progress. In this way we can de-risk subsequent lead-optimization programs and reduce time and costs. 

Lead Optimization 

Lead optimization requires fine-tuning of multiple parameters and our team has an excellent track record of progressing programs through to candidate selection. Either starting from lead compounds provided by the client or as a continuation of a previous Hit to Lead program, Welab is uniquely positioned to achieve the desired compound profiles, through the integration of Medicinal Chemistry with Pharmacology and ADME/Tox experts. Any type of optimization may be addressed, from single property to the whole lead profile, based on pre-defined target product profiles generated by the client or by Welab.  

In-house Proprietary SAR/SPR visualization tools for easy visualization of structure–activity and structure–property relationships of each chemical series allow fast iteration and project progression to identify suitable candidates in a time- and cost-efficient manner.