Round up of FBLD talks from CHI Drug Discovery Chemistry meeting in San Diego last week.
Lots of cool computational and experimental work, and a growing focus on covalent approaches
practicalfragments.blogspot.com/2024/04/ninete…

How to find molecules with the right personality for you!

practicalfragments.blogspot.com/2024/04/person…

Fragments lead to new binding modes, low P-gp efflux, and very good cellular activity against mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) needed to make nucleotides
practicalfragments.blogspot.com/2024/03/fragme…
ACS Publications Bio & Med Chem Content Research from JanssenUS

Fuller screens on full-length protein yields more hits
practicalfragments.blogspot.com/2024/03/fragme…
Astex researchers describe in-vivo active inhibitor against a notoriously difficult phosphatase and cancer target, SHP2 ACS Publications JMedChem

A round-up of the RSC BMCS conference in Cambridge UK #Fragments24
practicalfragments.blogspot.com/2024/03/fragme…
Chris Swain characterized fragments from >300 papers, sparking conversations around routes to covalency (@CossarPeter), thermodynamics, binding sites versus starting points, and much more

EFSL, a new fragment library to complement the  European Chemical Biology Library (ECBL)
In Royal Society of Chemistry Med Chem, the European Research Infrastructure Consortium profiles the EFSL library and describes the first screening projects
practicalfragments.blogspot.com/2024/03/the-eu…

Our fragments-in-the clinic list is updated!
At least 7 approved drugs started as fragments, with many more moving through clinical trials
practicalfragments.blogspot.com/2024/02/fragme…

Not quite as good as X-ray structures, but AlphaFold2 models work with hot spot finding software FTMap to suggest which proteins have promising ligandable sites
Boston University Biomedical Engineering ACS Publications
practicalfragments.blogspot.com/2024/02/hot-sp…

Photoaffinity fragments fish out the proteins they bind. Cleverly functionalized probes find new binding pockets in cell-based screens
practicalfragments.blogspot.com/2024/02/fragme…
Bristol Myers Squibb Chris Parker ForliLab Nature Chemical Biology

Covalent fragments across the proteome: tweaks across an MS screening process find thousands of reactive cysteines. TMT-ABPP requires less cell lysate to screen more compounds, in 96-well plates
practicalfragments.blogspot.com/2024/02/fragme…
Gygi Lab Qing Yu CellChemicalBiology

Covalent probes against a COVID-19 helicase: enantiomers functionalized with warheads separate reactivity from specificity to find inhibitors of nsp13
practicalfragments.blogspot.com/2024/01/covale…
Rockefeller University J. Am. Chem. Soc.

As covalent inhibitors gain popularity, drug hunters need to beware of pitfalls. Here's how to avoid them:
practicalfragments.blogspot.com/2024/01/covale…
American Chemical Society @jmedchem AssayQuant Technologies, Inc. UBuffalo Universität Tübingen

Puzzling out the rules of aggregation. The phenomenon muddies hit-hunting, but could help drug delivery.
Chen Chen @HellerLab find patterns that bring it towards rational drug design in Nature Communications
practicalfragments.blogspot.com/2024/01/what-m…

MiniFrags go electrophilic: RCNS MedChem Research Group analyze their new covalent screening library
practicalfragments.blogspot.com/2024/01/electr…

2024 is looking to be an annus mirabilis for fragment conferences, with four falling in the same year. Make travel plans for Boston, Brisbane, Cambridge and San Diego
practicalfragments.blogspot.com/2024/01/fragme…
Cambridge Healthtech Institute NovAliX ARC Centre for Fragment-Based Design  Monash Institute of Pharmaceutical Sciences FBLD Conference
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Our traditional end-of-year review of reviews: a distillation of >20 review articles relevant to fragment-based drug discovery published in 2023. Lots of crystallography, covalent fragments, PPIs and fun drug hunting
practicalfragments.blogspot.com/2023/12/review…

A large fragment library screen against IP6K1 produces a  modest hit without those pesky, CNS-impenetrant carboxylic acids (also, advancement without crystallography)
practicalfragments.blogspot.com/2023/12/fragme…
AstraZenecaUS Tyler Heitmann Johns Hopkins Medicine

A how-to guide for fragment screening against tough proteins by SPR. Nine constructs tested, quality controls in place, hits against all.
Helena Danielson + other biophysical luminaries Uppsala Biochemistry Uppsala University
practicalfragments.blogspot.com/2023/12/screen…

Why fused tetrahydroquinolines lead to dead-end hit-to-lead campaigns. Researchers Structural Genomics Consortium (SGC) solve a mystery and provide a valuable public service announcement
practicalfragments.blogspot.com/2023/11/beware…
ACS Publications Bio & Med Chem Content

7th fragment-based drug approved! AKT inhibitor capivasertib came from same fragment as two other approvals, and represents a 20-year marathon in targeting patients & optimizing dosing
practicalfragments.blogspot.com/2023/11/capiva…
Congratulations to The ICR, AstraZeneca & Astex!
@dereklowe