Richard Lee

This strategy allows for highly selective killing and minimizes the potential for mitotoxicity.

In this study, we demonstrate that it is possible to hijack intrinsic resistance mechanisms in Mycobacterium abscessus by utilizing the aminoglycoside resistance protein Eis2 to activate florfenicol amine in a prodrug approach.

Prodrug florfenicol amine is activated by intrinsic resistance to target Mycobacterium abscessus - Nature Microbiology Florfenicol amine hijacks intrinsic resistance in Mycobacterium abscessus, highlighting that antimicrobial resistance mechanisms can be harnessed for antibiotic activation.

Our new paper, which presents a novel strategy for targeting antibiotic resistance, is now available in Nature Microbiology.
www.nature.com/articles/s41...

Kinase atlas uncovers hidden layers of cell signaling regulation See how St. Jude scientists linked 117 kinases including EGFR tyrosine kinase to RNA polymerase II phosphorylation, revealing new targets for cancer therapy.

New findings on kinase phosphorylation of RNA polymerase II from the Ansari Lab!
bit.ly/Dabas_Pol2

Development of Pyrimido Pyridazine Analogs through Increased Whole Cell Target Engagement of the Dihydropteroate Synthase Pterin Binding Site in Gram-Negative Bacteria Dihydropteroate synthase (DHPS) is a critical enzyme in the folate biosynthetic pathway of bacteria, fungi, and protozoans. Sulfonamides successfully target the p-aminobenzoic acid (pABA) binding site...

Excellent research out of the Lee Lab by
@stjudegraduate
student Hannah Snoke!
bit.ly/SnokeACSID25
@stjuderesearch.bsky.social
#infectiousdiseases #DrugDiscovery

Collectively, it contributes to our overall understanding of Gram-negative permeability and demonstrates the applicability of target engagement as a metric for guiding SAR in antibiotic development.

This work increases our knowledge of the SAR of pterin-site inhibitors of DHPS, an important antifolate drug target, identifies 4367 as a validated cell-active DHPS inhibitor, and demonstrates the successful application of rapid HiBiT CETSA for drug discovery in Gram-negative bacteria.

This orthogonal assay platform was used to reevaluate the SAR of our Legacy pyrimido-pyridazine compound series against E. coli DHPS and to facilitate the design of an exploratory series of compounds with improved permeability, yielding a new lead with high cellular target engagement.

The results, when combined with surface plasmon resonance to measure target affinity and LC-MS/MS-based accumulation measurements, provide tractable medicinal chemistry data for lead development.

Key to this study is the development of a HiBiT thermal stability whole-cell target engagement assay that compares drug-induced thermal stabilization of the target in whole cells with that in cellular lysate.

Development of Pyrimido Pyridazine Analogs through Increased Whole Cell Target Engagement of the Dihydropteroate Synthase Pterin Binding Site in Gram-Negative Bacteria Dihydropteroate synthase (DHPS) is a critical enzyme in the folate biosynthetic pathway of bacteria, fungi, and protozoans. Sulfonamides successfully target the p-aminobenzoic acid (pABA) binding site...

Our new paper in ACS Infectious Diseases describes the development of a Gram-negative drug discovery platform to optimize drugs that engage their targets within the cytoplasm.
pubs.acs.org/doi/10.1021/...

You should check out the latest BBC Gardners world on Britbox if you like peonies

Now that the policy is out, we've rolled out an updated version of the story.

bsky.app/profile/maxk...

The GLP-1 Saga Continues, And How

GLP-1 agonists continue to be one of the most high-profile pharmaceutical battlegrounds. A look at recent developments:

China’s Biotech Advances Threaten U.S. Dominance, Warns Congressional Report Congress should invest at least $15 billion to support biotech research over the next five years and take other steps to bolster manufacturing in the U.S., the report said.

This!!! I hope someone in Washington is listening

www.wsj.com/tech/biotech...

12 drug candidates debut in San Diego Structures unveiled during first-time disclosures symposium

If you love drug candidates but weren't able to attend the #FirstTimeDisclosures symposium at #ACSSpring2025, check out my story about the session for @cenmag.bsky.social - with lots of cool-looking molecules.
cen.acs.org/acs-news/acs...

Updated Dashboard

jeremymberg.github.io/jeremyberg.g...

Added graphs for training grants (T mechanisms: T15, T32, T34, T35)

This looks (and is) bleak, but the time for most T mechanisms grants is a bit later. See bsky.app/profile/jere...

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A Bifunctional Degrader Reads Out in Phase 3

The first bifunctional protein degrader to deliver Phase III data! It seems to work, but people were definitely expecting more:

CBT rising stars in chemical biology is today, many outstanding talks from junior scientists