Students should be taught this paper alongside Ptashne's _A Genetic Switch_.
They should be forced to reckon with the fact that concepts they think they KNOW now will, by late in their careers, be seen as just a scratch in Nature's surface.
But much easier to buy a bit of stock than a bit of a house
Gosh who would have done that? Oh.
and I thought it was...
Yes!
Among many, many others.
Not so many have the $$ to sway Trump etc though
Oh. Nvm 😅
Immunology of GLP1s especially if it explores their potential in the autoimmune condition type 1 diabetes.
(or is that not what you meant by immunology of...?)
Sell the real stuff
Nobody voted for this.
Fewer grants ->fewer discoveries, fewer scientists, fewer treatments, more misery, less wealth
The only people who want this are those who want America to fail.
this is a business oppty Nikolay!
it's the only logical explanation
Another long article about the variety of uses for GLP1s that doesn't even mention type 1 diabetes.
I understand that most readers don't know that type 1 and type 2 are totally different conditions, but isn't educating people the point of such articles?
Also @danieljdrucker.bsky.social ...
Whoo boy, this happened to some international exchange scientists I worked with.
They drove into TJ by mistake, though - the trolley doesn't go there.
ChatGPT is surprisingly bad at helping scientists poison their labmates!
No, this article is not a joke...
#chemchat
@elizlanders.bsky.social 👍👍
And ok, I'm triggered by the description "GSK3-beta inhibitor."
Like, no way that stauro analog could tell the difference between GSK3-alpha and -beta.
C'mon!
Yes, let's celebrate any victory for patients. But these patients will be best served by complete characterization of the mechanisms their treatments are working through.
How else can we ensure the right patients are getting the right (combination of) drug(s)?
the warning signs just scream out from the original report. Stauro to GSK3b inhibitor *for pancreatic cancer* in one paper.
Like, back in 2009 didn't reviewers push back on this mechanism because of GSK3b's role in WNT/b-catenin- driven proliferation? And specifically pancreatic cancer??
Aha, I see @adesaurin.bsky.social is here. Thanks for publishing that paper about how elraglusib probably works.
🚶🏼
The ai tool is being developed by @jsheltzer.bsky.social and Google and may be of general interest to the #chemsky #chemchat crowd.
However, the mechanism is currently Unverified due to conflicting evidence regarding the driver of cytotoxicity. The drug's biochemical potency against GSK-3ß is relatively weak (I C50 ~ 710 nM) compared to its cellular efficacy. Recent high-quality studies have identified microtubules as a dominant off-target. Specifically, Elraglusib induces mitotic arrest and DNA damage via direct microtubule destabilization, a phenotype that is not replicated by other highly potent and selective GSK-3 inhibitors (e.g., CHIR-99021) Coats, 2024. Furthermore, functional studies indicate that the drug retains cytotoxicity even when GSK-3ß inhibition is accounted for, suggesting the microtubule effect is the primary driver of cell death Coats, 2024, Coats, 2023. Consequently, while Elraglusib is a GSK-3ß inhibitor, using it as a specific probe for GSK-3ß biology is flawed, and its therapeutic mechanism is confounded by off-target tubulin toxicity.
Selectivity Rationale: The drug is classified as PROMISCUOUS. Although early reports claimed selectivity against a kinase panel Gaisina, 2009, recent data reveals significant cross-class off-target activity on structural proteins (Microtubules) Coats, 2024. The drug affects two distinct biological systems (kinases and cytoskeleton) at therapeutically relevant concentrations, preventing a classification of "Selective."
Artificial intelligence agrees with my assessment 😉
compoundvalet.ai/Drug_Query
This is a useful tool that also brought me to this reference that shows the compound inhibits microtubule function aside from inhibiting kinases www.biorxiv.org/content/10.1...
Can't argue with clinical trial results.
But if this compound is acting selectively through GSK3-beta, I'll... be beyond surprised.
pubs.acs.org/doi/10.1021/...
it's just another demonstration of how unprepared America was for an anti-American presidential administration.
So much damage from such little effort.
You predict and wait and NIH... doesn't explain or make excuses?
