November 20, 2017
Small Molecule Discovery of the highest caliber at 15th Annual CBC Symposium
On Friday, November 17, the Chicago Biomedical Consortium (CBC) held its 15th Annual Symposium, focused this year on Small Molecule Discovery. Executive Director Jim Audia and Scientific Directors, Brian Kay (UIC) and Rick Morimoto (NU), served as hosts for the event. Interest in the meeting was extremely high as more than 300 registered for the meeting. Those who attended the event at UIC’s Forum were treated to an outstanding scientific program, a robust poster session with 40 poster presentations, an informative presentation covering the CBC’s newly launched Accelerator Award program over lunch, and a reception to conclude the event. The scientific program was impressive, with 6 talks representing a variety of small molecule drug discovery philosophies and perspectives from CBC institutions along with top tier academic, biotech and pharma researchers:
- The morning session began with Northwestern’s Rick Silverman who showcased his thoughtful approach leveraging mechanistic insights into GABA metabolic processing to identify and optimize GABA Aminotransferase inactivators for their therapeutic potential in epilepsy and substance abuse. Rick also showed the value of his broad Structure Activity Relationship studies from which he identified inhibitors of a loosely related enzyme, OAT, with therapeutic potential in hepatocellular carcinoma.
- Following Rick is never an easy task, but Vicky Richon from Ribon Therapeutics was clearly up to the challenge. Vicky introduced Ribon’s focus on small molecule inhibitors of the family of mono-ADP-ribosylating PARP enzymes, providing valuable insights into the company’s approach toward validation of novel biological targets and how they had established a robust platform for drug discovery. She also demonstrated the importance of their platform approach in driving insights into the disease biology and in defining the best opportunities for capturing the therapeutic potential in the target space.
- Ray Moellering from The University of Chicago completed the morning session by sharing exciting insights into glycolysis as a signaling hub which he has gleaned from his contemporary approach to proteomics. From Ray’s talk we learned that glycolysis is more than a source of energy and perhaps serves as an ancient regulator of metabolic signaling, important in a range of normal and disease-relevant physiological contexts. Further, we witnessed the power of proteomics studied in proper context in revealing insights important for both basic and translational research.
- The afternoon began with Greg Thatcher from UIC, illustrating the small molecule drug discovery approach taken by UICentre with a number of vignettes describing past and present projects. Operating with modest resources, Greg demonstrated promising results from their collaborative programs against a variety of targets, including selective estrogen receptor modulators and degraders, using monobodies to identify novel inhibitors of RAS, and tissue specific ABCA1 agonists to elevate ApoE4 function.
- Karin Briner from Novartis ably represented the large pharma research enterprise and offered glimpses into their approach toward small molecule drug discovery against historically difficult-to-drug targets. Her first example illustrated allosteric inhibitors of SHP2 phosphatase where compounds were found to stabilize the inactive form of the enzyme. Karin then described an exciting discovery of selective small molecule inhibitors of RNA splicing as a means of enhancing the expression of full length SMN protein for the treatment of spinal muscular atrophy.
- UCSF’s Brian Shoichet concluded the technical program with an overview of his computationally driven exploration of new GPCR biology in which libraries of billions of small molecules are efficiently docked against receptor structures to identify novel chemical matter which he then leverages into new biological insights. Some of the success is driven by the explosion of high resolution structural data in this space, but surprisingly even to Brian, the technique is increasingly successful even for orphan receptors or other targets supported only by homology models.
With the timing of the Symposium coinciding with the release of the RFA for CBC’s new Accelerator Award, Associate Director for Translational Activities, Nancy Tyrrell, provided an overview of the program and held a Q&A session during the lunch break. The event was well attended and, based on the level of interest shown, suggests that the Accelerator Award program will elicit a strong response in early 2018.
Photos by Brian Kay, CBC