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epistasisyesterday at 6:11 PM1 replyview on HN

Metastatic pancreatic cancer is the first indication for this class of RAS-inhibitor, but it certainly won't be the last, and it seems certain that there will be many many more cancers where this drug gets approved. There are mutations to activate KRAS in a substantial fraction of cancers across many organs, and but it's been such a hard protein to target with a drug that even decades ago I was told it was "undruggable."

What's going on with this new drug is a somewhat novel mechanism: instead of gumming up the enzymatic action of the protein, it acts as a glue between KRAS and a common "helper" protein, that then mucks up the RAS signalling. This sort of molecular glue mechanism has had a few examples built up over the past decade, but this is a really knock-it-out-of-the-park drug. Really amazing, and because of it lots of people are focusing lots of effort on how to discover more molecular glues.


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pfdietzyesterday at 10:48 PM

One downer about this drug is the absolutely horrific side effects, like "your skin feels like you've been dipped in acid" kind of horrific. Still, pancreatic cancer is just that bad, so maybe that's worthwhile.

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