Jan Domanski

Forbes 30U30, ex-CTO @Labstep, ex @DEShawResearch, ex @charmtherapeutx. Currently building frontier open-source co-folding models at @open_fold

[Jan Domanski @jandom_random]

@lucas_nivon This went really wild, honestly

[Jan Domanski @jandom_random]

@dbredesen @kevinace @aditharun_ @open_fold @sytses thanks @sytses is the first "founder mode oncology" story that came on my radar. he tried A LOT of stuff.

[Jan Domanski @jandom_random]

@kevinace @dbredesen @aditharun_ @open_fold @dbredesen @aditharun_ thanks for chiming in. all we've done is very simple scouting/characterization modeling, to have a structural understanding how these mutants push out lorlatinib. no new designs proposed (yet), nevermind the testing cascade any properties, incl ADMET

[Jan Domanski @jandom_random]

@ChrisHayduk Hahah @ChrisHayduk that's too kind – i don't know if there is any one "pipeline-in-a-person" maybe Mark Murko? It does take a village, and I'm just a coder/modeller – I a humbly bow to biologists, chemists, crystallographers, clinicians, pharmologlogists that i've worked with

[Jan Domanski @jandom_random]

@nacunaima dm'ed

[Jan Domanski @jandom_random]

Hey if this goes super viral, maybe somebody will thrown in $5m and we’ll make you an open-source next-generation inhibitor 🚀

[Kevin Wimer @kevinace]

@jandom_random @open_fold You're welcome sir. THANK YOU!

More from Jan the man here:
https://t.co/PYzFc9yoRk

[Jan Domanski @jandom_random]

@MeyersEdwin DM'ed!

[Jan Domanski @jandom_random]

Bare with me as I'm trying to learn how to use twitter/X... been absolutely overwhelmed with responses!

[Jan Domanski @jandom_random]

@BoJackCapital @fuckyourputs i need this cure as much as you do...

[Jan Domanski @jandom_random]

All this takes time, time that patients usually don't have.

We're yet to see an explosion of AI-enabled drugs – I helped make one such molecule, in trials now, so i'm pretty AI pilled but almost can't stand the hype around it. Show me the drugs! :D

It's just the start...

[Jan Domanski @jandom_random]

Huge thanks for the shout-out @kevinace , i'm blown away how much of the nuance you've managed to capture – making drugs is as complicated as making space ships, maybe more :-) It takes an absolute village!

(And lots of time and money – too much if you ask me)

[Kevin Wimer @kevinace]

So get this...a stranger DM'd me on X and offered to help design my backup cancer drug. For free!

His name is Jan Domanski @jandom_random. He runs science at @open_fold, an open-source AI model that predicts how proteins and drugs physically fit together.

My cancer is driven by one broken protein called ALK. Lorlatinib (the daily pill I take) jams itself into it and shuts it down. It's working. But resistance isn't an if, it's a when. The tumor mutates the pocket and the drug stops fitting.

So Jan started modeling it on his own time, burning his own tokens. He ran AI models against ALK and lorlatinib, mapping where the known escape mutations land.

And what did he find? Most of them hit right in the drug's pocket, swapping small pieces for bigger ones that physically block the drug. That's the good kind of bad news. A pocket problem is something you can design around.

But the normal route to a new drug is ~2 years and ~$4-5M just to be ready for human testing. Jan's dream is getting a medicine to one patient in ~1 month.

I'm not taking a homemade molecule while lorlatinib works. But if it ever fails....shit...I've got a guy!

I started posting actively on X just a few weeks ago and it has brought me together with the most amazing, generous people!

[Jan Domanski @jandom_random]

And the model is just the start: it's just a prediction, not the truth. You end up validating everything in the lab, initially just in vial, then a petri dish, then an animal, and then a human.

You have to design compound after compound, make sure it's safe and it works.

[Jan Domanski @jandom_random]

It was fun to be 6 hours delayed with Amtrak… let’s call it a cultural experience!

This is more of a useful speed to me!

Just over 300km, same distance as NYC to Boston. For 60 EUR, in 2.5h 😹 someone is getting screwed hard!

[Jan Domanski @jandom_random]

@eric_alcaide Everyone is learning here :P

[Lucas Meyer 🎙️ @meyer_lucas]

Patrick Stewart in the final scene on Star Trek: The Next Generation.

It’s extremely simple, but reveals so much of his character if you watched. Somehow his sense of duty and sensitivity, along with the admiration of his crew shines through.

RIP Captain.