<![CDATA[First PROTAC wins FDA approval.]]>First PROTAC wins FDA approval. This one targets certain metastatic breast cancers.

This is the first of a totally new type of drug that is set to revolutionize drug development.

The story of PROTACs is fascinating and a testament to fundamental research.

It starts with two lines of research including research one why thalidomide causes birth defects the other on how to harness cellular machinery for therapeutics.
1/🧵

https://www.nature.com/articles/d41573-026-00078-6

]]>https://board.circlewithadot.net/topic/96c1f8cb-8f89-4b22-8754-3ee7feb0b525/first-protac-wins-fda-approval.RSS for NodeFri, 15 May 2026 13:07:07 GMTSun, 10 May 2026 12:27:33 GMT60<![CDATA[Reply to First PROTAC wins FDA approval. on Sun, 10 May 2026 21:32:05 GMT]]>@failedLyndonLaRouchite

Well I am reaching the stage in my career where I expect that 10 years ago me will be scooping today me.

]]>https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116552415671674041https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116552415671674041Sun, 10 May 2026 21:32:05 GMT<![CDATA[Reply to First PROTAC wins FDA approval. on Sun, 10 May 2026 20:30:06 GMT]]>@MCDuncanLab

just me
all the greats take in ideas and then a few months later think it is their idea

so you are in great company !!

this is based on two years as a postdoc at MIT biology; YMMV

]]>https://board.circlewithadot.net/post/https://mas.to/users/failedLyndonLaRouchite/statuses/116552171951866856https://board.circlewithadot.net/post/https://mas.to/users/failedLyndonLaRouchite/statuses/116552171951866856Sun, 10 May 2026 20:30:06 GMT<![CDATA[Reply to First PROTAC wins FDA approval. on Sun, 10 May 2026 13:51:36 GMT]]>@epicdemiologist

That’s one target of interest.

]]>https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550605004253102https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550605004253102Sun, 10 May 2026 13:51:36 GMT<![CDATA[Reply to First PROTAC wins FDA approval. on Sun, 10 May 2026 13:50:28 GMT]]>@MCDuncanLab Oh my god, if we could send them after prions!!!

]]>https://board.circlewithadot.net/post/https://wandering.shop/users/epicdemiologist/statuses/116550600500829584https://board.circlewithadot.net/post/https://wandering.shop/users/epicdemiologist/statuses/116550600500829584Sun, 10 May 2026 13:50:28 GMT<![CDATA[Reply to First PROTAC wins FDA approval. on Sun, 10 May 2026 13:37:13 GMT]]>No harm done I hadn’t put his idea as my own at least in writing. And I came up with my own approach and I identified a small molecule inhibitor of my process. This let me getting my faculty job, but I don’t work on small molecules anymore. It was a fun time.

]]>https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550548407398766https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550548407398766Sun, 10 May 2026 13:37:13 GMT<![CDATA[Reply to First PROTAC wins FDA approval. on Sun, 10 May 2026 13:35:56 GMT]]>I came up with this amazing idea of using the cell quality control system to rapidly destroy my protein. I was super excited and I talked to somebody who worked on the quality control system, and shared my idea.

She asked so like the system that Ray Deshaise is working on? And I realized that I had seen a talk a year or two earlier where Ray had described the system and I had forgotten it and taken it as my own idea.

]]>https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550543371929345https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550543371929345Sun, 10 May 2026 13:35:56 GMT<![CDATA[Reply to First PROTAC wins FDA approval. on Sun, 10 May 2026 13:34:38 GMT]]>Funny related story. When I was a postdoc, I wanted a quicker way to inhibit the protein I was studying. We had been using something called temperature sensitive mutations, which were slow or we could have used a regulated promoter, which was also slow.

]]>https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550538285767570https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550538285767570Sun, 10 May 2026 13:34:38 GMT<![CDATA[Reply to First PROTAC wins FDA approval. on Sun, 10 May 2026 13:24:05 GMT]]>@dch

I’m hoping i didn’t get some small details wrong, I’m partly working from memory partly from references some of which I’m only accessing the free content since I’m not at work.

Will update if I find mistakes.

]]>https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550496785204248https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550496785204248Sun, 10 May 2026 13:24:05 GMT<![CDATA[Reply to First PROTAC wins FDA approval. on Sun, 10 May 2026 13:12:19 GMT]]>@MCDuncanLab thanks for this thread!

]]>https://board.circlewithadot.net/post/https://bsd.network/users/dch/statuses/116550450533748997https://board.circlewithadot.net/post/https://bsd.network/users/dch/statuses/116550450533748997Sun, 10 May 2026 13:12:19 GMT<![CDATA[Reply to First PROTAC wins FDA approval. on Sun, 10 May 2026 13:10:52 GMT]]>What is so exciting about PROTACs is they can be designed to destroy almost protein, so their usefulness isn’t limited to cancer therapies, there are PROTACs in the works for neurodegenerative diseases and autoimmunity.

It’s really an amazing time to be in bioscience (there’s bad stuff happening to the scientific enterprise esp in the US but I’ll leave this thread mainly positive)

🧵/end

]]>https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550444800977089https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550444800977089Sun, 10 May 2026 13:10:52 GMT<![CDATA[Reply to First PROTAC wins FDA approval. on Sun, 10 May 2026 13:04:09 GMT]]>To do this, they wanted to make a chemical with two faces one that bound the quality control system and one that bound the protein they wanted to destroy. Both are difficult chemistries to build.

But the work on thalidomide revealed a ready made chemical that bound the quality control system, this spurred a whole ton of academic and biotech research that is just now bearing its first fruits.

5/🧵

]]>https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550418393356397https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550418393356397Sun, 10 May 2026 13:04:09 GMT<![CDATA[Reply to First PROTAC wins FDA approval. on Sun, 10 May 2026 12:59:40 GMT]]>And this is where it intersects with another line of research. In the early 2000s, Kathleen Sakamoto, Craig Crews and Ray Deshaies described the first attempt to hijack the cells quality control system to target a protein they chose.

The process worked in principle, but they needed to find a better way to bring the quality control system to the protein they wanted to destroy.
4/🧵
https://pmc.ncbi.nlm.nih.gov/articles/PMC37474/

]]>https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550400762061754https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550400762061754Sun, 10 May 2026 12:59:40 GMT<![CDATA[Reply to First PROTAC wins FDA approval. on Sun, 10 May 2026 12:50:19 GMT]]>The target was a protein known as cereblon. Cereblon is a protein that is part of the cell’s quality control system. It flags other proteins for destruction.

https://www.science.org/doi/10.1126/science.1177319 (Sorry paywalled)

3/🧵

]]>https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550364032545571https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550364032545571Sun, 10 May 2026 12:50:19 GMT<![CDATA[Reply to First PROTAC wins FDA approval. on Sun, 10 May 2026 12:44:00 GMT]]>You may recall the thalidomide tragedy, a wonder drug for severe morning sickness that caused some babies to be born with severely shortened limbs.

The drug was later repurposed as an anticancer drug, but the question remained why does it cause birth defects and why is it effective as an anti cancer drug.

Decades of research went into answering that question. In 2010, a paper authored by Takumi Ito Hideki Ando and others working with Hiroshi Handa revealed the target of thalidomide. 2/🧵

]]>https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550339164688205https://board.circlewithadot.net/post/https://mstdn.social/users/MCDuncanLab/statuses/116550339164688205Sun, 10 May 2026 12:44:00 GMT<![CDATA[Reply to First PROTAC wins FDA approval. on Sun, 10 May 2026 12:33:52 GMT]]>@MCDuncanLab Great news. Paywalled, but Wikipedia helped (except for the thalidomide link). And I'll have to make a minor edit there 🙂

]]>https://board.circlewithadot.net/post/https://circumstances.run/users/Szescstopni/statuses/116550299326510628https://board.circlewithadot.net/post/https://circumstances.run/users/Szescstopni/statuses/116550299326510628Sun, 10 May 2026 12:33:52 GMT