Discovery and Optimization of a WDR5 Chemical Probe
Rima Al-awar,
Director,
Ontario Institute For Cancer Research
The mission of the Drug Discovery Program at OICR is to efficiently translate cancer-related academic discoveries into novel oncology therapies that will have a significant impact on the cancer patient population. Coupling the team’s drug discovery expertise with the local academic setting we hope to leverage the strengths of each and create a unique and collaborative research environment from which potential leads and chemical probes can be derived.
Deregulation of Mixed lineage leukemia 1 (MLL1) is often associated with acute myeloid and lymphoid leukemias and was proposed as a novel therapeutic target. WD40 repeat protein 5 (WDR5) is a component of the multiprotein MLL1 complex that is essential for its methyltransferase activity. Thus, therapeutic intervention of the WDR5/MLL1 interaction may lead to possible novel therapeutic agents for MLL-dependent leukemias. Our collaboration with the Structural Genomics Consortium (SGC), using a structure-based design approach, has identified compounds that bind to WDR5 with low nanomolar affinities.
Part 1 of the presentation will describe our collaborative model and Part 2 will give an example of a successful collaboration that led to the identification of a chemical probe for WDR5.
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