Ultra centrifugation for the non-Jedi.

A really impressive campaign by some of the best medicinal chemists in the business.

Admittedly, I do, too

This reviewer has me looking at lots of GPCR structures. Feels like @mikefeigin.bsky.social had something to do with this… (he didn’t, pretty sure).

Or a kinase?!

The crystallography community would like to inquire as to the whereabouts of any that may be available for microseeding. Ethically, consensually, and humanly sourced of course.

Structural Studies of Fourth-Generation EGFR Inhibitors Reveal Insights into Selective T790M and C797S Targeting Inhibitors targeting mutant EGFR remain a persistent need in combating drug resistance in non-small cell lung cancer. To better understand the molecular factors involved in targeting T790M and C797S…

SBGrid's eLife paper received a citation in January from @heppnerd.bsky.social at @ubuffalo.bsky.social in @acsmedi.bsky.social Letters: Structural Studies of Fourth-Generation EGFR Inhibitors Reveal Insights into Selective T790M and C797S TargetingArticle link copied!

More here: buff.ly/6K0CRwv

📢 Call for Nominations - Portoghese Lectureship

This Award is to recognize two outstanding early career investigators conducting research in the field of Medicinal Chemistry.

📅 Deadline: Dec 1, 2025
🔗 Make a Nomination here: americanchemical.co1.qualtrics.com/jfe/form/SV_...

Congrats to Abdul!

RSC Medicinal Chemistry promotional graphic for the Kinases themed collection.

📢We are delighted to share our latest themed collection on Kinases, guest edited by Hayley Binch, @heppnerd.bsky.social, Meizhong Jin and Philip Jones!

Explore the articles that make up this fantastic collection, here👇
pubs.rsc.org/en/journals/...

#chemsky 🧪

An Error Occurred Setting Your User Cookie OR SEARCH CITATIONS

SBGrid's eLife paper received a citation in August from @heppnerd.bsky.social from @sunyofficial.bsky.social at Buffalo in Journal of Medicinal Chemistry: Profiling and Optimizing Targeted Covalent Inhibitors through EGFR-Guided Studies.

Read more here: buff.ly/VwDYVh2

#SBGrid #ScienceMatters

Profiling and Optimizing Targeted Covalent Inhibitors through EGFR-Guided Studies Targeted covalent inhibitors (TCIs) are actively pursued in drug discovery due to their prolonged target engagement and clinical efficacy. Although kinetic parameters provide a path to their optimizat...

New paper out today in J. Med. Chem. pubs.acs.org/doi/10.1021/...

Honestly, this is the content we all need right now.

Thanks for your highlight, Erik!

Enhancing Selectivity and Potency of SNAr Covalent Inhibitors of NADPH Oxidase Enzymes Dysregulated reactive oxygen species (ROS) are implicated in various diseases, positioning NADPH oxidase enzymes (NOXs) as attractive therapeutic targets. However, progress in tool compound discovery ...

Sharing our most recent research published in #JMedChem @acsmedi.bsky.social @pubs.acs.org pubs.acs.org/doi/10.1021/...

An honor to be included in this class of impressive investigators!

a young man is smiling and talking about bingo . ALT: a young man is smiling and talking about bingo .

RIP Val Kilmer who gave us Chris Knight and the classic (we can drop “cult”, right?) “Real Genius”. A timeless treasure that hits home again and again.

Clearly something NY should strongly consider!

Drug Discovery and Development Faces an Ominous Future from NIH Indirect Costs Rate Cuts

Drug Discovery and Development Faces an Ominous Future from NIH Indirect Costs Rate Cuts
pubs.acs.org/doi/10.1021/...

Drug Discovery and Development Faces an Ominous Future from NIH Indirect Costs Rate Cuts

Drug Discovery and Development Faces an Ominous Future from NIH Indirect Costs Rate Cuts pubs.acs.org/doi/10.1021/...

Ascertaining a Structural Basis in Drug Discovery and Development OR SEARCH CITATIONS

New editorial in #JMedChem on “Ascertaining a Structural Basis in Drug Discovery and Development.” @pubs.acs.org @acsmedi.bsky.social

pubs.acs.org/doi/10.1021/...

Deep Cuts to Medical Research Funds Could Hobble University Budgets Grants from the National Institutes of Health come with additional money for overhead. Proposed funding cuts would leave colleges with large budget gaps.

NEW: The N.I.H. will cut about $4 Billion from federal research grants that support cancer, virus and heart disease research.

#Project2025 called for the cuts to end subsidies to "leftist" university agendas.

www.nytimes.com/2025/02/07/u...

NIH cuts billions of dollars in biomedical funding, effective immediately The move halts a large slice of money for most universities and research institutions virtually overnight, imperiling vital research in everything from cancer to heart disease.

NIH has cut billions of dollars in biomedical funding, effective immediately
The move halts a large slice of money for most universities and research institutions virtually overnight, imperiling vital research in everything from cancer to heart disease.

www.washingtonpost.com/health/2025/...

NIH cuts billions of dollars in biomedical funding, effective immediately The move halts a large slice of money for most universities and research institutions virtually overnight, imperiling vital research in everything from cancer to heart disease.

Another assault on US competitiveness at a time when biomedicine is roaring with innovation, an own-goal in a high-stakes international tournament. Of course the real losers are American people needing medicines and cures.

www.washingtonpost.com/health/2025/...

You finally get to one that I would truly resonate with…

Protein Data Bank (PDB) Deposition Service struggling today.

What a great way to round out a year! Thanks to Gunda Georg for hosting and the many members of the medicinal chemistry department, @umnchemistry.bsky.social, and others for the great meetings and opportunity to share our story.

Hi Bluesky 👋 We're looking forward to sharing our departmental news on this new platform. Please spread the word that we've joined!

We’re excited to announce that the ACS Division of Medicinal Chemistry is now on Bluesky! 🦋🔵

Follow us for updates on awards & fellowships, meetings, webinars, editorials, and all things MEDI. Stay connected with the latest news from the Division! 📣

Tilting the Scales toward EGFR Mutant Selectivity: Expanding the Scope of Bivalent “Type V” Kinase Inhibitors Binding multiple sites within proteins with bivalent compounds is a strategy for developing uniquely active agents. A new class of dual-site inhibitors has emerged targeting the epidermal growth factor receptor (EGFR) anchored to both the orthosteric (ATP) and allosteric sites. Despite proof-of-concept successes, enabling selectivity against oncogenic activating mutations has not been achieved and classifying these inhibitors among kinase inhibitors remains underexplored. This study investigates the structure–activity relationships, binding modes, and biological activity of ATP-allosteric bivalent inhibitors (AABIs). We find that AABIs selectively inhibit drug-resistant EGFR mutants (L858R/T790M and L858R/T790M/C797S) by anchoring a methyl isoindolinone moiety along the αC-helix channel of the allosteric site. In contrast, related Type I1/2 inhibitors target wild-type EGFR but are less effective against resistant mutants. This shift in selectivity demonstrates that mutant-selective AABIs classify as “Type V” bivalent inhibitors.

Our most recent work discovering bivalent Type V kinase inhibitors in collaboration with Stefan Laufer Eberhard Karls Universität Tübingen published in J. Med. Chem.
pubs.acs.org/doi/full/10....