*JEFFREY COULL

Defining the Rules That Will Enhance the Cell Permeability and Oral Bioavailability of Macrocycles

Challenge: Encycle Therapeutics has developed a novel synthetic platform to design enhanced peptide macrocycles called nacellins. Nacellins molecules approximate the dimensions of beta turns extremely well and, although reminiscent of conventional cyclic peptides, exhibit substantially improved passive membrane permeability, as well as stability in the gut and inside cells. However, further chemical modifications of nacellins are needed to render them … Read More

*PATRICK VERMETTE

Novel Methods to Evaluate Cardiac Activity of Pharmaceuticals: Identifying New Therapies and Predicting Cardiac Toxicity

Challenge: A major problem with protein-based therapeutics is their immunogenicity, i.e. their tendency to trigger an unwanted immune response against themselves. This leads to the activation of immune cells and secretion of anti-drug antibodies (ADA) that may contribute to an inactivation of the biologics and cause adverse clinical events. Therefore, there is a need in the pharmaceutical industry for assays to … Read More

CHERYL ARROWSMITH

Developing open access protein degradation tools for drug discovery

Challenge: PROTACs (PROteolysis TArgeting Chimeras) are bifunctional drugs that recruit a ubiquitin E3 ligase to a targeted protein, thereby catalyzing poly-ubiquitylation of the target and its subsequent degradation by the proteasome. PROTAC induced protein degradation offers advantages over classical enzyme inhibition: it acts via a catalytic instead of occupancy-based mechanism and shows superior efficacy with fewer off-target side effects and … Read More

TRAIAN SULEA

RecyTag technology for extended half-lives of small biologics

  Competition: Programme EXPLORE 2013 Funding: $499,000 / 2 years Platform technology aimed at increasing the half–life of small biologics by conjugating FcRn-binding molecules. Protein-based therapeutics, also called biologics, have recently made significant inroads into the pharmaceutical market, and are being used to treat chronic diseases and cancer. In addition to acting potently and specifically on their molecular targets, efficacious … Read More

*ANDREI YUDIN

Cycloinformatics: A platform for rapid production of medium-sized macrocycles as protein-protein interaction probes

  Competition: Québec / Ontario Program 2011 Funding: $1,000,000 / 2 years Beginning: September 2014 (COMPLETED PROJECT) A new class of cyclic peptide structures called macrocycles could reach intracellular drug targets to modulate protein-protein interactions currently inaccessible to most pharmaceutical agents. The potential to reach an untapped goldmine of new targets has attracted a great deal of interest and excitement in biopharmaceuticals. … Read More

TOMAS BABAK

Genetic interactions studies to better establish efficacious drug targets

  Competition: EXPLORE Program 2014 Funding: $300,000 / 2 years Beginning: June 2015 A major challenge for pharmaceutical companies is identifying efficacious drug targets. Genetic interactions, where the effects of disrupting multiple genes at once are measured, enable unbiased interrogation of functional relationships between any genes of interest. When applied to many genes systematically, an interaction network emerges, and this … Read More