Practical_Fragments (@PracticalFrag) | Aguea

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Practical_Fragments @PracticalFrag

Jun 9

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

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Jun 1

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

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May 27

From fragment to clinic: the story of VVD-214, covalent allosteric inhibitor of WRN helicase, and part 3 of 3 for our round-up of fragments against this flexible, fascinating cancer target practicalfragments.blogspot.… @bmsnews @VividionRx @ACSPublications

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May 18

Crystallographic fragment screen finds cryptic pockets on oncology target WRN, protein co-folding software suggests binding modes to generate covalent inhibitors practicalfragments.blogspot.…

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May 11

Finding fragments when a protein has many conformations: Merck team finds and advances fragments against synthetic lethal cancer target WRN helicase practicalfragments.blogspot.…

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May 4

Watch out for X-ray structures that assume every protein has a ligand. A new analysis suggests one-third should show partial binding. Just one-tenth in the PDB actually do: practicalfragments.blogspot.… @Structure_CP @StJude

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Apr 27

Latching into and breaking out of a cryptic pocket: Efforts toward a chemical probe of anti-virulence bacterial target DsbA practicalfragments.blogspot.… @ACSPublications @MIPS_Australia

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Apr 21

A wrap-up of fragment-relevant talk at San Diego's sunny @CHI_Healthtech practicalfragments.blogspot.… GPCRs, NMR, hit optimization, platform development, covalent drugs, direct-to-biology, computational screening, molecular glues, and more

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Apr 15

Targeted protein degradation in cancer cells? Fragment screen plus optimization yields cell-active ligand on the E3 end for a selective PROTAC: practicalfragments.blogspot.… @AmerChemSociety @JMedChem

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Apr 6

SARS-CoV-2s papain-like protease is a tough target. Researchers @VanderbiltChem advance fragment hit non-covalently and covalently: practicalfragments.blogspot.… @ACSMedChemLett @JMedChem @AmerChemSociety

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Apr 1

The laxest ligand efficiency metric, at last! practicalfragments.blogspot.…

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Mar 23

A practical metric from @VividionRxto to help weed out nonspecific, generally-reactive covalent ligands: Ligand reactivity efficiency (LRE) practicalfragments.blogspot.… @ACSPublications

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Mar 16

Artifacts against a SARS-CoV-2 target exposed! A cautionary tale shows the importance of compound resynthesis and purification practicalfragments.blogspot.… @ACSPublications

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Mar 10

Before trusting a chemical probe or advancing a lead compound, a selectivity check is crucial. But cell-free (DiscoverX @EurofinsGroup ) and cell assays (NanoBRET @promega) can yield different answers for kinases. practicalfragments.blogspot.… @Chemical_probes @ACSPublications

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Mar 2

A technique to find the binding mode of fragment-sized millimolar binders? Hydrogen/deuterium exchange MS (HDX-MS) gets at least 2/3 for CyclophilinD: practicalfragments.blogspot.…

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Feb 23

Dimer detection, binding kinetics, and more: A wealth of biophysics techniques from @novalix_pharma conference in San Diego: practicalfragments.blogspot.…

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Feb 17

3D fragment hit rates are lower, but perhaps advancement goes faster. A shapely scaffold yields an impressive hit for the histamine H1 receptor. practicalfragments.blogspot.… @RoySocChem

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Feb 9

A fragment becomes a trimer and a potent inhibitor of lipoprotein(a) formation. How a rule-of-3 compliant fragment became an unconventional but promising phase 3 candidate for CV disease: practicalfragments.blogspot.… @ProfSNicholls ⁩ ⁦@MonashVHI⁩⁦ @Nature⁩ @EliLillyandCo

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Feb 2

Crystallographic SAR Hits from high-throughput X-ray screens of crude mixtures can be broken down into fingerprints that identify new binders that crude extract X-ray screening miss practicalfragments.blogspot.… @UniofOxford @DiamondLightSou @FrankvonDelft

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Jan 26

Fragment merging finds submicromolar binders for a kink in a leucine zipper practicalfragments.blogspot.… In @NatureComms, @Novartis researchers find binders for a difficult melanoma target, the transcription factor MITF

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