While I’ve since transitioned into new ventures, I’m thrilled to see this recent work being shared as an oral presenation by Zheng Wang at AACR 2025. A novel approach to ALK degradation using brain-penetrant molecular glues — a compelling strategy to address resistance and CNS progression in ALK+ cancers
If you’re attending AACR this week, here’s a session worth catching:
🧠 Brain-penetrant molecular glue degraders targeting ALK via a novel degron: a potential therapeutic approach for ALK-positive NSCLC
📍 Where: Room S404 – McCormick Place South (Level 4)
🗓️ When: April 29, 2025 | 3:40–3:55 PM CST
One of the coolest things about molecular glues is their ability to create (almost by magic) these hitherto and previously unbeknownst surface areas.. that weren’t even considered “druggable.” Nothing against the nomenclature here, but somehow "undruggable" doesn't quite make sense to me. If you are actually now targeting it, isn't it now 'druggable'? But I digress..
Now once these new surfaces are recognized by something like the E3 ligase system it can result in degradation of the protein they're interacting with. Then there are the classical kinase inhibitor targets in oncology, such as ALK. Typically targeting the orthosteripc pocket the protein uses endogenously with ATP. But with glues, there might not be any limits. This is something akin to an allosteric pocket..but stamping that allosteric pocket in other parts of the protein.
If you're headed to AACR, I highly recommend checking it out. And if you’re curious about ALK-targeted drug design, I’ve got some reflections coming soon on the blog — stay tuned.
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From the Alkhemist
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