A screen of carboxylic-acid containing fragments followed by X-ray informed linking and warhead addition produces promising chemical probe against DNA-repair protein RAD52  practicalfragments.blogspot.… @J_A_C_S @london_lab @DiamondLightSou

Validating DEL hits by diffraction. 'Mologram' chips functionalized with oligos capture complementary strands bound to small molecules. If those molecules bind proteins, differences in diffraction are detected. practicalfragments.blogspot.… @ACSPublications

My take on #DiscoveryOnTarget2026 features covalent binders, direct-to-biology screens, and "traditional" fragment-based drug discovery. Fun that two decades on the cutting edge has become traditional! practicalfragments.blogspot.… @CHI_Healthtech @BostonDOT

Super-sized fragments? Researchers @Novartis curate the Scope library with ~50K  elaboration-enabled 200-400 MW molecules to capture advantages of fragment and full-size screening practicalfragments.blogspot.…

How useful is design? Roth, Fraser & Shoichet labs synthesize & test >250 single-atom changes for ligands against 6 proteins and find that >10% of analogs have potency boosts of at least 10-fold, without using any structural insights. practicalfragments.blogspot.… @zenbrainest @nature

Strategies for covalency: @VividionRx recognize covalent potential on inflammasome target NLRP3, scan proteome to find cryptic site, assess promiscuity, improve selectivity, and present a chemical probe in @BrJPharmacol practicalfragments.blogspot.…

Researchers train software to hunt out cryptic pockets practicalfragments.blogspot.… @OECloud @J_A_C_S

Fragment-screening finds cryptic (and more) sites for synthetic lethal cancer target ARID1B practicalfragments.blogspot.… @Relay_Tx  @PNAS

Fragment-based hunt for an RNA helicase inhibitor. Finding a probe against DHX8 required orthogonal screens and a willingness to see that the initially most promising hit was not actually the most progressable practicalfragments.blogspot.… @ACSPublications  @ICR_London

New site-specific HDX-MS method using hydrogen-deuterium exchange improves resolution to single amino acids, and should apply to a broader range of proteins than X-ray, NMR, and cryoEM practicalfragments.blogspot.… @ACSPublications

Therapeutic target PTP1B attracts both drug hunters and artifacts. Universität Tübingen researchers took a fragment screen with a fluorescence readout through careful paces to sort fake-outs from actual hits practicalfragments.blogspot.…

Does Fsp3 (aromaticity) affect a hit's potential? Researchers @Merck analyze millions of their molecules for permeability, lipophilicity, solubility, off-target activity and more to revisit an abiding question practicalfragments.blogspot.… @rohanmerchant1 @Charles_chem @ACSPublications

What's that ligand's affinity for that kinase? Your assay might affect your answer. practicalfragments.blogspot.… @B_R_Peterson compares isolated proteins with cell lysates and live cells @OhioState @J_A_C_S

Differential scanning fluorimetry seems a handy tool for covalent ligands practicalfragments.blogspot.… @BrJPharmacol @WeizmannScience

Researchers at @NovartisScience find that make-on-demand libraries ease follow-up work for fragment screening by fluorine NMR practicalfragments.blogspot.… @EnamineLtd  @ChemMedChem

An updated list of fragment events in 2026 and 2027 - at Practical Fragments! practicalfragments.blogspot.… @RSC_BMCS @BostonDOT @CHI_Healthtech xitter.cf/FBLDconference

Fragment linking often better in theory than reality, but @gyuriakiraly + @DiamondLightSou + more combined covalent hit with nearby binder to get micromolar inhibitor from only 3 molecules practicalfragments.blogspot.… @ChemMedChem

Great potential in uncharted chemical space. Whether a molecule is 'bio-like' doesn't seem to matter much for hit-rates or selectivity, suggesting surprising abundance of potential drugs practicalfragments.blogspot.… @ACSPublications @zenbrainest @ACSBioMed

Serendipity in fragments: A screen for hits against the hard-to-drug, plasma membrane-recruiting Pleckstrin Homology Domain finds an unusually reactive lysine, and a covalent hit against BTK practicalfragments.blogspot.… @ACSBioMed @JMedChem @Cambridge_Uni

Sometimes a classic warhead is not actually a warhead. Serendipity with hub protein 14-3-3: practicalfragments.blogspot.… @ACSBioMed @RichardDoveston @Leicesterchem @ACSMedChemLett