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To be eligible for consideration this Application form must be submitted on cache-challenge.org latest 23:59 CEST on 15th June 2024.
Please note that by submitting this Application and, if accepted for participation, by making one or more Submissions to this CACHE Challenge, you are agreeing on behalf of yourself and your organization to the CACHE Terms of Participation, found here: CACHE Terms of Participation.
Please fill in all fields in this form in order to be eligible to participate.
Applications will be pre-screened at CACHE to ensure that the Applicant research group or company has published in the field or otherwise has appropriate qualifications. Applications will then go through a double-blind peer-review process where the Computational Approach Description(s) submitted below will be available to the reviewers. Each Applicant that passes the pre-screen stage will be asked to review the quality of the Computational Approach from five other Applicants (without identifying Applicants) and to verify that the Computational Approach Descriptions are sufficiently detailed that an expert in the field could readily understand the Applicants’ prediction strategies. Applications that pass the double-blind peer-review stage will be reviewed by an independent committee convened by CACHE that will select up to 25 Applicants to participate and make submissions of binding predictions to this CACHE Challenge1. All selected Participants will be anonymized2.
1. CACHE has no obligation to accept any particular Application but, resources permitting, will strive to accept all Applications with viable Computational Approach Descriptions and appropriate Applicant qualifications, as determined by CACHE in its discretion.
2. Disclosing your publications may reveal your identity to visitors. They may use this information to determine from preliminary results disclosed at the end of Round #1 whether you advanced to Round #2, and how efficient your method was overall at the end of Round #2.
As noted above, please note that by submitting this Application and, if accepted for participation, by making one or more Submissions to this CACHE Challenge, you are agreeing on behalf of yourself and your organization to the CACHE Terms of Participation, found here: CACHE Terms of Participation.
CACHE will cover 100% of the costs of testing compounds experimentally. 100% of the costs of procuring compounds (either make-on-demand or custom-synthesized compounds) will be covered by participants. To lower the costs, CACHE will agree with Enamine on a preferred bulk price. CACHE will cover 100% of the costs for eligible Canadian academics and 50% for eligible Canadian SMEs through Strategic Innovation Fund awarded by the Canadian government.
The information in this section will be maintained confidential unless you click otherwise below, or are in the top three performing Participant’s in this CACHE Challenge.
Details of the corresponding applicant (to whom emails will be sent):
If your application is accepted:
You will have three months starting July 7th 2024, with a Submission deadline of October 7th 2024, to select or design up molecules occupying one or multiple subcavities of the histone binding groove of the SETDB1 triple Tudor domain (TTD). You will be provided with free access to Simulations-Plus. Compounds with predicted solubility < 100 µM according to Simulations-Plus or MW > 550 Da willnot be tested. All experimental data will be sent back to you, barring unforeseen circumstances, by April 15th 2025.
In addition to submitting their predictions by October 7th 2024, Participants using de novo design approaches at their own cost will be responsible for having their predicted compounds and associated analytical spectra showing >95% purity received at CACHE by December 15th 2024.
This section will be used for double-blind peer-review and will be disclosed on cache-challenge.org anonymously (except as described above) after all participants have submitted their first compound selection:
By November 1st 2024, barring unforeseen circumstances, you will receive an SDF file with the 2D structure of all compounds selected by all Participants at the hit identification phase, but without any experimental data. You will be asked to predict up to 100 actives among these compounds by February 1st 2025.
This section will be used for double-blind peer-review and will be disclosed on cache-challenge.org anonymously (except as described above) after all merged selection participants have submitted their merged selection.
Please describe how you will predict up to 100 active compounds from the merged selection of around 2000 compounds predicted in Round 1 by all participants. This is an important step of CACHE challenges where all participants predict hits from the same library. Please be precise and specific in your method description. “As above” is not an acceptable answer. Thank you.
By April 15th 2025, barring unforeseen circumstances, you will have received all experimental data for the compounds that you selected that were successfully delivered to CACHE. From among the hits (K0 < 50 µM) that emerge from your work, you will be asked to select by June 15th 2025 an additional 50 chemical analogs to explore the structure-activity relationship of these experimental hits. Your file must contain the ID and SMILES string of each compound as well as the parent compound (which will be used as positive control). You will be required to pay Enamine or any other provider directly. CACHE will then test them experimentally, measure the solubility and purity of the highest affinity hits, and send all data back to you, including the K0 of active molecules by December 15th 2025.
If compounds are custom-synthesized, participants will be responsible for synthesis at their own cost and for having the compounds and associated analytical spectra showing > 95% purity received at CACHE by September 15th 2025.
This section will be used for double-blind peer-review and will be disclosed on cache-challenge.org anonymously (except as described above) after all hit-optimization participants have submitted their selection of optimized compounds.
On March 15th 2026, barring unforeseen circumstances, CACHE will publicly release the anonymized list of participants and their origin (academia, biotech, pharma etc.). As described above, Participant identity will be de-anonymized if they are a top three performer or have consented to release of their identity above. Information about a Participant’s software and/or reproducible workflows will be released if the Participant has consented above. For all Participants the following will be released:
Methods will be evaluated and ranked using a traffic-light scoring scheme detailed in Ackloo, S., et al. Nat Rev Chem 6, 287-296 (2022).
As noted above, please note that by submitting this Application and, if accepted for participation, by making one or more Submissions to this CACHE Challenge, you are agreeing on behalf of yourself and your organization to the CACHE Terms of Participation, found here: CACHE_Terms_of_Participation.
