Challenge: Because they are involved in so many physiological processes, G protein coupled receptors (GPCRs) are engaged by roughly 40% of marketed drugs and remain a prime target for the development of new therapeutics. To test the activity of drug candidates, understanding their action on their target in living animals is essential. However, this goal…
Challenge: One of the most promising strategies for discovering our future medications is via fragment-based lead discovery (FBLD). FBLD involves the screening of libraries of small molecules to first identify weak binders, essential to activate or inhibit a target protein involved in a particular disease. These binders are then synthetically matured to larger, more potent…
Challenge: G protein-coupled receptors (GPCRs) are the largest target class for approved drugs. Identification of new drug candidates has relied exclusively on high-throughput assays which track binding properties and are limited to a restricted number of signaling pathways. GPCRs are highly dynamic proteins that undergo numerous conformational changes upon receptor association with ligands and related…
Challenge: Proteins are the main effectors of cell activity and cardinal indicators of cell phenotype and response to stimuli such as drugs. Whereas sequencing technologies currently allow for broad and efficient genomic and transcriptomic profiling, multiplexed protein detection technologies are either prohibitively slow and expensive, limited in scope due to reagent cross-reactivity, or both. Critically,…
Challenge: Drug discovery by high-throughput screening of candidate compounds is usually limited in efficacy as their functional potential is not assessed in relevant biological systems, such as patient cells, during this first selection; new platforms are needed that enable functional testing within specific biological systems. An example of protein trafficking that would benefit from such platforms is Alpha-1 antitrypsin deficiency (ATD), an orphan disease, whose behaviour in the endoplasmic reticulum (ER) is complex, rendering the design of therapeutic candidates difficult. Solution:…
Challenge: Drug discovery by high-throughput screening of candidate compounds faces challenges and needs the development and validation of specific platforms. An example of complex diseases that would benefit from such platforms is cystic fibrosis, a lung disease caused by genetics and aggravated by air pollution. An immediate response of bronchial epithelial cells to pollution is the downregulation of…
Competition:EXPLORE Program 2015Funding:$300,000 / 2 yearsBeginning:April 2016 Protein-protein interactions (PPIs) play a crucial role in nearly all cellular processes. Protein complexes have been implicated in many debilitating human diseases, from cancer to viral infections. PPIs generally contain broad, shallow, and relatively featureless binding sites, hence they have historically been perceived as ‘undruggable’ targets in drug…
Challenge: Triple-negative breast cancer (TNBC) accounts for 15 to 20 % of all breast cancer patients, but for about 25 % of all breast cancer deaths. There is currently no targeted treatment for TNBC, while only about 30 % of TNBCs are sensitive to conventional therapies. In addition, no more than 50 % of HER2-positive…
Challenge: Ovarian cancer is a leading cause of cancer death in women. Only a fraction of women diagnosed with ovarian cancer will respond to current therapies. In order to better tailor treatment to each patient, personalized medicine has turned to biomarkers that statistically evaluate the chances of a drug to be effective for a patient.…
Challenge: Acute myeloid and lymphoid leukemias (AML and ALL) are lethal hematologic cancers that affect both children and adults. Despite major progress in the treatment of pediatric AML and ALL, relapse and disease progression in patients with high-risk disease remain common problems. Furthermore, current drugs and radiotherapy treatments are associated with a wide array of…