Curious How Drug Discovery Can Be Accelerated by DEL‑ML?

Then I would like to invite you to read our paper in RSC Chem. Biol. which also represents my first corresponding authorship:

“𝘋𝘪𝘴𝘤𝘰𝘷𝘦𝘳𝘺 𝘰𝘧 𝘢𝘯 𝘦𝘹𝘲𝘶𝘪𝘴𝘪𝘵𝘦𝘭𝘺 𝘴𝘦𝘭𝘦𝘤𝘵𝘪𝘷𝘦 𝘞𝘋𝘙5 𝘤𝘩𝘦𝘮𝘪𝘤𝘢𝘭 𝘱𝘳𝘰𝘣𝘦 𝘢𝘤𝘤𝘦𝘭𝘦𝘳𝘢𝘵𝘦𝘥 𝘣𝘺 𝘢 𝘩𝘪𝘨𝘩-𝘲𝘶𝘢𝘭𝘪𝘵𝘺 𝘋𝘌𝘓–𝘔𝘓 𝘏𝘪𝘵”

(DEL-ML = DNA Encoded Library + Machine Learning)

Highlights
✅ We demonstrate power of DEL-ML and how it can accelerate drug discovery and probe development
✅ WDR5 is therapeutically relevant target (modulates c-MYC oncogene)
✅ LH168 is more than another WDR5 inhibitor
💊 High in cellulo activity (EC50 = 10 nM)
💊 Excellent proteome-wide selectivity
💊 Thorough characterization in orthogonal assays (ITC, SPR, NanoBRET…)
💊 Long residence time!
✅ We also developed structurally similar negative control LH222
✅ …as well as click-ready analogue for bifunctional molecules such as PROTACs

LH168 has been approved by our external scientific committee as high-quality WDR5 chemical probe and became a part of SGC chemical probe library.

⚗️ You can already buy LH168 from chemical vendors.

🍀 But the best thing is that you might get a free sample via collaboration with SGC Frankfurt ❗

Full manuscript: https://pubs.rsc.org/en/content/articlelanding/2025/cb/d5cb00109a

Leave your comments under my LinkedIn post here.

Behind this succesful story is hard work of many colleagues from The Structural Genomics Consortium (SGC) or ETH Zurich. Thank you for your dedication and work! (Lasse Hoffmann, Christopher Lenz, Frederic Farges, Serah Kimani, PhD, Johannes Dopfer, Sabrina Keller, Martin Schwalm, Hanna Holzmann, Andreas Kraemer, Levon Halabelian, Aiping Dong, Fengling Li, Irene Chau, Matthias Gstaiger, Susanne Muller-Knapp and Stefan Knapp.

#ChemicalBiology #WDR5 #DELML #ChemicalProbe #SGC #DNAencodedLibrary #DrugDiscovery