Toronto, ON, Canada (August 2, 2017) – Dr. Linda Penn’s lab at Princess Margaret Cancer Centre and Cyclica Inc., both located in Toronto, Canada, will collaborate on a special project utilizing the Ligand Express™ drug discovery informatics platform. Dr. Penn’s group specializes in molecular oncology (Dr. Penn holds a Canada Research Chair Tier 1 appointment), with a focus on the Myc-related pathways and mevalonate (cholesterol) metabolic pathways and their role in promoting cancer. Exploration into the modulation of mevalonate pathway revealed cancer cell sensitivity when they were treated with statin drugs in combination with an FDA approved drug (dipyridamole).
The mechanism by which dipyridamole, a small molecule agent, synergizes with statin to induce apoptosis is still an active area of investigation. “We are excited to see the results generated by the Ligand Express platform”, stated Dr. Penn, “we have an idea of how this novel synergistic interaction is taking place, but need a focused approach to continue forward. Cyclica’s technology could be the tool that helps us make a breakthrough with this project, which can have a major impact on cancer treatment”.
Cyclica’s Ligand Express™ platform evaluates a small molecule’s polypharmacology to gain critical understanding about an agent’s biological activity. By generating a list of probable interacting proteins, the technology enables researchers to refine their research programs to identify critical details about an agent’s mechanism-of-action. For research in Dr. Penn’s lab, Ligand Express™ will help identify proteins linked to the mevalonate pathway that may be responsible for dipyridamole’s synergistic activity with statin drugs. With knowledge of the mechanistic target in hand, other agents can be identified or designed to increase efficacy of the drug combination.
“Working with Dr. Penn was a perfect fit for our technology given our unique value add in target deconvolution,” remarked Naheed Kurji, President and CEO of Cyclica, “we are well positioned to help guide her research towards the answers she needs to move a new therapeutic avenue forward. We are continually privileged to support Canadian research with world-class scientist such as Dr. Penn. The ongoing efforts in our own backyard exemplify our commitment to the Canadian Health R&D ecosystem, and are crucial efforts in our go global strategy.”
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Cyclica Inc. has developed, validated, and patented a structure-based proteome-wide screening platform, Ligand Express™, that currently features PROBEx (proteome-screening), SWITCHx (ligand effect prediction) and DIVEx (systems biology & drug-protein interactomes). Ligand Express™ is unique in that it is a drug-centric platform. For a small molecule ligand, Ligand Express™ automatically generates an intelligent list of ligand-protein interactions by searching through a large proprietary database of all available structurally characterized proteins. The platform provides a panoramic view of a small molecule ligand to better understand on- and off-target interactions, and is valuable in finding novel desirable or undesirable targets. By gaining insights into a ligand’s polypharmacology, Cyclica’s clients can identify unknown targets, prioritize lead candidates, elucidate adverse effects, and understand repurposing opportunities. www.cyclicarx.com
About the Penn lab:
The Penn Lab exploits the molecular drivers of cancer to stop it in its tracks. Two major and distinct biological pathways are being explored in the Penn Lab, Myc signalling and the mevalonate (cholesterol) pathway. Myc is a gene that regulates the expression of other genes, with important roles in a number of processes including cell death. Myc mutations are very common—over half of human cancers—and understanding its role in tumour cells is a major area of investigation. The Penn Lab are exploring statin drugs, which are normally used to control cholesterol, to trigger tumour cells to self-destruct. Understanding the mechanisms of these drugs could lead to a new tool in the arsenal against cancer—one that is already approved for use in humans, fast-tracking its use in patients.
For more information:
Application Scientist, Cyclica