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


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


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


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


Cycloinformatics: A Platform to Rapidly Produce Macrocyclic New Chemical Entities to inhibit Protein- Protein Interactions

Challenge: While small molecules have delivered great value for targets featuring small binding cavities, their use against challenging targets with featureless interfaces are quite limited. Although such targets are better tackled by biologics, such compounds usually have poor cell penetration and limited oral bioavailability. There is thus a need to design biologics, such as peptides, allying high information contents (chemically … Read More