Hit Identification[/vc_column_text][dt_gap height=”10″][vc_column_text]Projects with quality starting points make faster progress and have lower attrition rates than projects that start with poor quality leads.
Identifying a quality lead is the project’s first committed step. Whether by HTS, fragments, virtual screening, or any other hit-finding methodology, identifying quality hits is critical. Selection of inferior starting points (typically due to the allure of high initial potency) generally leads to failure at a later (and much more expensive stage) for reasons that should have been predicted.
Hit identification methods. Various companies have emerged around a particular screening methodology. In comparison, we aim to use whichever approach is most suitable for each particular target and in special cases we have used two approaches in parallel. We refer to our routinely-used methods as our Hit-ID toolbox:[/vc_column_text][vc_column_text]
Emphasis is on quality and understanding, not numbers of compounds[/vc_column_text][/vc_column][vc_column width=”1/2″][dt_gap height=”10″][dt_gap height=”10″][vc_column_text]We identify leads that have the following:
- Clearly validated activity ideally in two or more orthogonal assays. Strong initial potency is
helpful, but not critical since this is the parameter that is usually most easily improved.
- Excellent chemical properties including low lipophilicity, high solubility, and high ligand efficiency.
- Favorable risk assessment of the scaffold including understanding related scaffolds and potential off-target (polypharmacology) activities, and intellectual property position.
- Clearly demonstrated scope for optimization to assure that progress can be made according to realistic and definable timelines.
We do not advance leads if optimization is expected to “fix” intrinsic liabilities.
Citations: Albert, JS; Fragment-based Lead Discovery in “Modern Approaches to Lead Discovery” Wiley Publications, 2010, 105 (Link)[/vc_column_text][/vc_column][/vc_row]