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Our Medicinal Chemistry group is an integral part of most types of CDoT drug discovery projects, ranging from target validation to compound optimization towards development candidates. While synthesis of new analogs begins after hit identification, we recognize the importance of involving chemists early in projects to increase the chances of success. Our medicinal chemistry team is also available in a consultancy role to assist in target drugability assessment and partners with the Ó³»­´«Ã½ legal team to determine intellectual property strategy and develop patent applications as appropriate.

As projects advance through the various stages of discovery, our chemists play integral roles in:

Screen Development and Support

• Identification of prior art or tool compounds which can be utilized to validate assays and biological hypothesis
• Collaboration with biologists to develop discovery project assay flowcharts
• In collaboration with our automation and screening teams, support of biologists in choosing the screening method(s) consistent with a project’s resources and requirements
• Determination of the most appropriate libraries for project screens, be they traditional high-throughput screens (from focused to diverse), fragment screens, or DNA-encoded libraries
• Implementation of robust computational processes to conduct virtual screens, incorporating machine learning-based approaches as appropriate to expand the scope of screening beyond existing physical libraries and assays

Screen Follow-up

• Hit validation and development of initial structure-activity relationships (SAR)
• Development of structure-activity relationships within a series  to optimize compounds towards project milestones, such as in vivo POC or lead optimization
• Assessment of a molecule's inherent properties (e.g., solubility, lipophilicity)
• Assessment of a compound’s biological behavior in in vitro pharmacokinetic (ADME) studies
• Advice on identifying appropriate CRO resources for compound synthesis, and establishing and managing close relationships with these CROs to design and synthesize the relevant small molecules
• Assistance in compound profiling in assays both internally/externally

Development of In Vivo Ready Molecules

• Working closely with our in vivo experts to design appropriate PK studies to understand and support in vivo target engagement and efficacy experiments
• Helping our in vivo team to develop formulations and compound supply to deliver on key proof of concept studies