Lightnews — Scholar-powered news

Keith Hornberger @krhornberger.bsky.social · 16h

(still) Master of the House

Keith Hornberger @krhornberger.bsky.social · 16h

500 years after Paracelsus, who famously and presciently understood this problem, in many corners, scientists continue to struggle with the basic tenet: the dose makes the poison. The ivermectin story is a good reminder for all of us to practice good pharmacological hygiene in our own work.

1 2

Keith Hornberger @krhornberger.bsky.social · 16h

I’ve written before at the Other Place about how molecular discrimination approaches a limit in biological systems. This is a problem as old as the hills, and is far from limited to ivermectin. It’s why I often take a hard line when the chemical tools folks report only work at uM concentrations.

Keith Hornberger on X: "Time for another pharmacology tweetorial on another layer of the selectivity problem: drug promiscuity. Both the things we can control, and the things that are out of our hands thanks to good ol’ Mother Nature. 1/ https://t.co/GGnmhqQCSF" / X

Time for another pharmacology tweetorial on another layer of the selectivity problem: drug promiscuity. Both the things we can control, and the things that are out of our hands thanks to good ol’ Mother Nature. 1/ https://t.co/GGnmhqQCSF

x.com

1 1

Keith Hornberger @krhornberger.bsky.social · 16h

3. Is an aggregator whose “activity” frequently disappears with detergents added

4. Does not achieve uM drug levels when dosed in humans, so has no hope of working even if the uM activity wasn’t an artifact

1

Keith Hornberger @krhornberger.bsky.social · 16h

In brief, the authors (re)show that ivermectin:

1. Is cytotoxic, probably through membrane perturbation, at the uM levels reported for SARS-CoV-2 inhibition, in contrast to the nM concentrations used for its intended anti-parasitic MOA

2. Is an assay interference compound in typical Alpha assays

1

Keith Hornberger @krhornberger.bsky.social · 16h

Some good weekend reading. If you thought we’d put the final nails in the coffin of ivermectin as a Covid treatment, you’d be right. But this Perspective goes the extra mile to put the coffin in a lead-lined box and sink it to the bottom of the ocean. 🧵

Membrane Perturbations and Assay Interferences by Ivermectin Explain Its In Vitro SARS-CoV-2 Antiviral Activities and Lack of Translatability

The antiparasitic drug ivermectin was proposed as a repurposed drug for the treatment of SARS-CoV-2 infection based on in vitro studies, but proved ineffective in high-quality clinical trials. When ex...

pubs.acs.org

1 1 7

Keith Hornberger @krhornberger.bsky.social · 3d

You’ve also just learned something valuable about the culture of whichever company told you this, so maybe it’s for the best

1 2

Keith Hornberger @krhornberger.bsky.social · 3d

Sorry this happened to you KC. I would have hoped they could offer something more constructive. This kind of elitism was rampant when I first got into industry 23 years ago. It’s improved today - but far from gone

2 3

Keith Hornberger @krhornberger.bsky.social · 3d

Discovery of BRD9 Molecular Glue Degraders That Spare Cardiomyocytes

Molecular glue degraders (MGDs) represent a class of drug-like small molecules that induce targeted protein degradation (TPD) by promoting selective protein–protein interactions. MGDs offer a promisin...

pubs.acs.org

3

Reposted by Keith Hornberger

C&EN (Chemical & Engineering News) @cenmag.bsky.social · 5d

The 2025 #NobelPrize in Chemistry has been awarded to Susumu Kitagawa, Richard Robson and Omar M. Yaghi “for the development of metal–organic frameworks.” Stay tuned for the full story to come! cen.acs.org/people/nobel...

#ChemNobel #Chem #Chemistry #chemsky 🧪

The 2025 chemistry Nobel goes to MOFs

Susumu Kitagawa, Richard Robson and Omar M. Yaghi win the prize for developing metal–organic frameworks

cen.acs.org

2 66 150

Keith Hornberger @krhornberger.bsky.social · 5d

🤦‍♂️

Keith Hornberger @krhornberger.bsky.social · 5d

I sincerely hope that LNPs get their due someday and aren’t forgotten in the wake of the mRNA vaccine medicine Nobel. They make the whole thing actually work!

1 1

Keith Hornberger @krhornberger.bsky.social · 5d

7

Keith Hornberger @krhornberger.bsky.social · 5d

Fleischmann died over a decade ago so is ineligible. And anyway, maybe we can let the physicists have that one even though they’re electrochemists 😂

1

Keith Hornberger @krhornberger.bsky.social · 5d

😂

Keith Hornberger @krhornberger.bsky.social · 6d

It’s Nobel Prize in Chemistry Eve, and you know what that means - it’s time for the annual survey!

Who will win this year’s chemistry Nobel? Wrong answers only.

a cartoon hand is pressing a red button that says wrong answer

ALT: a cartoon hand is pressing a red button that says wrong answer

media.tenor.com

15 7 18

Keith Hornberger @krhornberger.bsky.social · 6d

Rational design of the linkers in targeting chimeras

Targeting chimeras (TACs), such as PROTACs, LYTACs, AUTACs, and ATTECs, have emerged as promising strategies for selectively degrading proteins, including undruggable targets. These approaches leverag...

pubs.rsc.org

2

Keith Hornberger @krhornberger.bsky.social · 9d

If true, this really worries me a lot. It fuels my worst fears that AI tools will drive brain rot by encouraging us to take our hands off the wheel and not worry so much about what’s right or wrong anymore.

2 1 4

Keith Hornberger @krhornberger.bsky.social · 9d

I recently visited a PUI where some faculty told me that AI tool use to complete homework is rampant and the students are getting (wrong) info from “studying” with chemistry YouTubers. And then totally failing exams because no homework practice and no studying. Thoughts? Corroboration?

1 3 2

Keith Hornberger @krhornberger.bsky.social · 10d

Translational Research on the Oral Delivery of the Cytotoxic PROTAC Molecule via Tumor-Targeting Prodrug Strategy for Triple-Negative Breast Cancer Treatment

In the present work, we have identified a proteolysis targeting chimera (PROTAC) molecule that potently and selectively degrades CDK4, CDK6, and CDK9, inhibiting triple-negative breast cancer (TNBC) c...

pubs.acs.org

1

Keith Hornberger @krhornberger.bsky.social · 11d

ChEMBL is a great — and free — resource for the community. Here’s the latest.

Drug and Clinical Candidate Drug Data in ChEMBL

Drug and Clinical Candidate Drug Data in ChEMBL

ChEMBL is a large-scale, open-access, FAIR database of bioactive molecules with drug-like properties. ChEMBL 35 contains 17,500 approved drugs, and drugs that are progressing through the clinical deve...

pubs.acs.org

1 4

Keith Hornberger @krhornberger.bsky.social · 13d

GSPT1 degraders: research progress, development strategies and challenges

Dysregulation of GSPT1 which is a critical translation termination factor plays an important role in oncogenesis and cancer progression. However, GSPT…

www.sciencedirect.com

2

Keith Hornberger @krhornberger.bsky.social · 13d

Enzyme-Activated Sugar-Coated Bifunctional Degraders

Targeted protein degradation with compounds like proteolysis targeting chimeras (PROTACs) directs disease-associated proteins to the E3 ligase ubiquitin-proteasome system for removal. However, commonl...

pubs.acs.org

1 2

Keith Hornberger @krhornberger.bsky.social · 17d

Optimizing linker rigidity to improve intracellular behavior of PROTACs targeting hematopoietic prostaglandin D synthase

Proteolysis-targeting chimeras (PROTACs) are emerging as powerful tools for targeted protein degradation. Among the key factors influencing their efficacy, linker design plays a critical role by affec...

pubs.rsc.org

1

Keith Hornberger @krhornberger.bsky.social · 17d

I have to admit, I don’t keep a supply of ginger syrup just lying around most of the time. I’ve already consumed an entire door shelf in the fridge with various syrups, and my wife might kill me if I make any more!

1