30th November 2023
Registration will open soon for the first CACHE Symposium on 6th – 7th March 2024 in Toronto.
A poster session is planned in the evening on 6th March – we hope many will register and present their data in addition to our great line-up of speakers.
The detailed programme will be announced shortly.
26th October 2023:
We are thrilled to announce the inaugural CACHE Symposium, set to take place in Toronto, Canada, on March 6th (PM) and March 7th (AM), 2024. This symposium will bring together leading experts in the field of computational chemistry and artificial intelligence to share their insights and experiences during the first CACHE Challenge.
John Moult, our keynote speaker and initiator of Critical Assessment of Structure Prediction (CASP), will deliver a retrospective on CASP computational challenges, providing deep insights into this dynamic field.
Among our speakers, experts from the pharmaceutical industry will discuss the value of benchmarking challenges from the industry perspective, and invited CACHE #1 participants will present their computational methods, share results, and offer general impressions.
Save the date and stay tuned for the forthcoming agenda! Further details will follow as the event approaches.
We look forward to welcoming you all to the 1st CACHE Symposium in Toronto.
23rd September 2023:
Experimental data on 800 hit expansion compounds for CACHE Challenge #1, Round 2 have been shared with participants. The CACHE hit evaluation committee is currently reviewing the aggregated experimental data on all compounds and results will be made public on 20th December 2023.
15th September 2023:
In total 1921 compounds selected by 23 CACHE Challenge #4 participants have been ordered from Enamine. These novel chemical scaffolds must bind to the closed conformation of the CBLB TKB domain with a KD below 30 micromolar. Experimental validation will follow.
16th August 2023:
All 1739 compounds shipped by Enamine in Kyiv and predicted by 25 participants to CACHE Challenge #3 to bind SARS-CoV-2 NSP3 Mac1 are now received in Toronto. Screening by HTRF and DSF (at the SGC Toronto) and by crystallography at UCSF's Fraser lab is about to begin.
9th August 2023:
The preliminary results from the experimental validation of 1957 compounds for CACHE Challenge #2, Round 1 have been posted. Forty-six compounds selected by 18 participants are advancing to the hit-expansion phase (Round 2).
1st August 2023:
23 participants to CACHE Challenge #4 have submitted their predicted ligands targeting the TKB domain of CBLB, an E3 ubiquitin-protein ligase. Compounds will be ordered from Enamine and validated experimentally.
9th July 2023:
Preliminary experimental data on the primary screen by SPR was sent to CACHE Challenge #2 participants.
19th June 2023:
714 chemical follow-ups of compounds of interest selected by 18 participants to CACHE Challenge #1 arrived last week from Ukraine. Experimental screening against LRRK2 to begin this week. All data expected to be released in December 2023.
2nd June 2023:
Based on the double-blind peer-review, 25 groups from biotech, pharma and academia are invited to participate in CACHE Challenge #4 and will now predict hits to the TKB domain of CBLB, an E3 ubiquitin-protein ligase and immuno-oncology target with an inhibitor in the clinic.
3rd April 2023:
800 hit-expansion compounds selected by 18 CACHE Challenge #1 participants to interrogate the SAR of their primary LRRK2 hits were ordered from Enamine.
CACHE Challenge #3 participants submitted their predicted hits for SARS CoV-2 Nsp3.
10th March 2023:
1951 compounds predicted by 25 participants from biotech, pharma and academia shipped by Enamine in Kyiv just arrived in Toronto. Experimental validation for binding to SARS-CoV-2 NSP13 is about to begin.
9th March 2023:
Call for applications is open for CACHE Challenge #4 finding ligands targeting the TKB domain of CBLB, an E3 ubiquitin-protein ligase with hundreds of compounds reported in the patent literature from multiple organizations, all chemically related. CACHE participants are asked to predict compounds with new scaffolds.
26th January 2023:
6 biotechs and 19 academics topped the double-blind peer review to join CACHE Challenge #3. They will predict novel chemical scaffolds targeting the MACRO domain of SARS-CoV-2 NSP3.
17th December 2022:
Experimental data on 1955 compounds was sent back to participants to CACHE Challenge #1. The data included binding to the WDR domain of LRRK2 assessed by SPR, BLI, ITC, 19F NMR. The solubility and absence of aggregation of the compounds was measured by DLS. 73 compounds selected by 18 participants were nominated to advance to the 2nd stage of the challenge: hit expansion. Until now, no ligand was known for the WDR domain of LRRK2. All data and compound structures will be publicly released here at the end of the challenge, around December 2023.
2nd November 2022:
Call for applications is open for CACHE Challenge #3 finding ligands targeting the macrodomain of SARS-CoV-2 NSP3, a target with dozens of fragments and inhibitors in the PDB, open to both receptor-based and ligand-based approaches.
1st November 2022:
Experimental data on the primary screen by SPR of 1955 compounds targeting the WDR domain of LRRK2 was sent back to CACHE Challenge #1 participants. Over 400 compounds were cherrypicked for dose response and > 120 compounds selected for validation with orthogonal binding assays, which we hope will be completed by December 1st.
23rd September 2022:
25 groups from academica, biotechs and pharma are participating in CACHE Challenge #2. The participants were selected by a double-blind peer-review process out of 41 candidates and will predict hits for the SARS-CoV-2 helicase, NSP13.
22nd June 2022:
Call for applications is open for CACHE Challenge #2, focused on the RNA-binding site of the SARS-CoV-2 helicase, NSP13. This is the most conserved drug binding site across all coronavirus proteins, and a promising target for a universal coronavirus drug. Fragment-bound structures are in the PDB.
13th May 2022:
The description of the computational methods used by the 23 participants in CACHE Challenge #1 are available on our website, revealing a great diversity of approaches (AI, physics-based, docking, pharmacophore, fragments, generative models, …).
9th May 2022:
23 teams participating in CACHE Challenge #1 have submitted their predicted hits: a total of ~2000 compounds that CACHE will purchase and test experimentally. All data will be publicly released.
7th March 2022:
25 teams from 7 biotechs, 1 pharma and 17 non-profit organizations are selected to participate in CACHE Challenge #1 composed of 3 steps:
1- Computationally select up to 100 compounds that CACHE will purchase and experimentally test for their ability to bind the WDR domain of LRRK2
2- Computationally screen the ensemble of compounds selected by all participants and predict which are active
3- Computationally select up to 50 analogs of your experimentally validated hits. CACHE will purchase and test them experimentally
24th February 2022
Background and updates on CACHE will be provided by multiple speakers at EUbOPEN, Target 2035 Webinar, 24th Feb. 2022
15th February 2022:
The CACHE white paper endorsed by co-authors from 8 pharmas and over 15 universities, biotechs and global non-profit organizations is published in Nature Reviews Chemistry
1st February 2022:
Double-blind peer review of applications for CACHE Challenge #1 is initiated. Each candidate reviews 5 applications. An independent committee uses the resulting grades to select the top 25.
1st December 2021:
Call for applications is open for the first CACHE challenge, focused on the WDR domain of LRRK2, the most commonly mutated gene in familiar Parkinson’s Disease. Apo crystal structure is in the PDB. No ligand reported so far.