We’re pleased to launch the eighth CACHE Challenge, which is now accepting applications. The deadline to apply is April 16th, 2026.
The CACHE Challenges, made possible by the Government of Canada’s Strategic Innovation Fund, offer an open competition platform in which researchers from academia, industry, and nonprofits are invited to deploy their best computational methods to predict small molecules that will bind to a predefined target linked to a specific disease. Their predictions are then evaluated and benchmarked in a state-of-the-art laboratory, by our partners at the Structural Genomics Consortium (SGC). All the benchmarked results are shared openly and publicly with the world, and all chemical structures are made available without patent to all.
The scientific challenge
CACHE Challenge #8 invites participants to identify chemically novel molecules that bind to the substrate-recognition pocket of GID4, a protein involved in cellular protein quality control. This binding site is well characterized, having been observed interacting with both natural peptide substrates (ex: structure 6CCT) and a potent, selective small-molecule probe (structure 7SLZ), providing a strong structural foundation for computational design.
GID4 plays a role in the cell’s protein disposal system: it recognizes specific proteins that are damaged or no longer needed and directs them to the cellular protein degradation system. By selectively engaging this recognition process, researchers can potentially harness the cell’s own machinery to remove disease-causing proteins.
Why this target?
GID4 is an attractive target for computational drug discovery. Its binding pocket is clearly defined and structurally validated, yet only a limited number of chemical scaffolds have been explored so far, meaning there is opportunity for novel molecule discovery.
Importantly, GID4 can be targeted by PROTACs (proteolysis-targeting chimeras), a new class of drugs designed to eliminate harmful proteins rather than simply inhibit them. PROTAC-based therapies are being explored across a wide range of diseases, including cancer, neurodegenerative disorders, and infectious diseases, particularly for targets that have historically been difficult to drug.
While PROTACs have not yet reached clinical approval, the field is advancing rapidly. The development of robust ligands for proteins like GID4 could help unlock this therapeutic approach and expand the range of diseases that can be treated by targeted protein degradation.
Participation cost
Compound procurement: Participants should expect to pay approximately CA$100 per compound.
Experimental validation: CACHE will cover 100% of the costs of testing compounds experimentally in a state-of-the-art laboratory at the Structural Genomics Consortium (SGC).
Canadian Participants
- Conscience will fund up to 50% of the costs for eligible Canadian academics and companies
- Funding caps per round: up to $75,000 for SMEs and $50,000 for academics
- Funding is reimbursement-based, meaning costs must be incurred and paid before reimbursement
- Successful applicants must enter into a Ultimate Recipient agreement with Conscience
To learn more about the benefits of participating in a CACHE Challenge, check out our blog post featuring repeat CACHE participants.
How to apply
Apply via the CACHE Challenges website at the link below. The deadline to apply is April 16th, 2026.
CACHE welcomes participants from around the world and is committed to improving equity, diversity and inclusion in computational drug discovery. We strongly encourage applications from individuals and teams from groups that are underrepresented in our research community.
