Life Science Spotlight
Recent advances in drug discovery, synthetic and medicinal chemistry, chemical biology and related areas.
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Can DCAF1 Keep Up With Cereblon?
Every second paper on PROTACs repeats the same phrase that lack of small molecule ligands capable of recruiting various E3 ligases…
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Catching a Nascent Radical in a Picosecond for Stereoretentive sp3-sp3 Radical-Radical Cross-Coupling
Some problems in chemistry are so old that we stopped challenging them and accepted them as facts of life. A good…
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Novel Naphthyl Bioisostere for Your Med-Chem Toolbox
What do FDA approved drugs propranolol, naproxen and terbinafine have in common? They all contain a naphthalene moiety, which is a…
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Biocatalytic Cascades Enable Manufacture of the Macrocyclic Peptide Enlicitid
Enlicitide decanoate (MK-0616) is a beautifully complex macrocyclic (not so small) peptide (or rather pseudo-peptide). This 1720 Da heavy beauty with…
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How Do PROTACs Actually Get Into Cells?
Big molecules, big permeability issues. All medicinal chemists know that well. No wonder that many scientists in drug discovery were skeptical…
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Rewriting the Ubiquitin Code: Sugars and Metabolites Enter the Picture
For decades, ubiquitin has been considered almost exclusively as a protein tag. Its C-terminal Gly-Gly motif forms isopeptide (or occasionally thio-/oxy-ester)…
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Hijacking ERAD for Targeted Degradation of Transmembrane Proteins
Although PROTACs hijacking cytosolic E3 ligases have been reported to degrade certain trans-membrane (TM) proteins (including EGFR, GPCRs, and PD-L1), It…
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Bypassing E3 Ligases by 26S-UIDs: Novel Modality for Targeted Protein Degradation
PROTACs and molecular glue degraders are the front runners in the area of targeted protein degradation (TPD), with several clinical candidates….
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Nickel-Mediated Protein Arylation Inside Living Cells
While transition metals drive powerful bond-forming reactions in synthetic chemistry, their use for covalent modification of biomolecules has been largely underexplored…
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When One Catalytic Cycle Is Not Enough
The installation of alkyl substituents through C(spĀ³)-C(spĀ³) coupling is in high demand in synthetic and medicinal chemistry. While some strategies towards…
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Accessing Spirocyclic Ethers via Chemical Cascade with Carbyne Equivalents
We chemists love building molecular complexity efficiently and in as few steps as possible. This allows us to transform readily accessible…
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Alcohols as Building Blocks for C-C Cross Coupling
Until now, direct activation of the CāO bond was an unresolved problem, mainly due to high dissociation energy (approximately 96 kcal/mol)…
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Cracking the Oncogenic Star Player KRAS
KRAS has been in the focus of cancer research for quite some time as it has been recognized as a key…
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Design, Development and Optimization of RIPK1 Degrader
Optimization of PROTACs for in vivo applications is non-trivial, thought not impossible. A nice example on this topic represents freshly published…
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Rewriting Chemistry Textbooks: From Alkene to Alkyne via Hetero-Diels-Alder Reaction
Although Hetero-Diels-Alder will play a central role, I am not going to speak about gender. Not today. Instead, I would like…
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Breaking New Ground in mRNA Degradation
About 85% of disease-related proteins lack suitable binding pockets for conventional drug discovery. While RNA-targeting approaches like siRNAs have shown promise…
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Nano-PROTACs Are Gaining Traction
The field of PROTACs continues to evolve. A recent Nature Communications paper describes another self-assembling nano-PROTAC that co-degrades androgen receptor (AR)…
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Is It PROTAC or Molecular Glue? … It Is Both!
Researchers often steer the design of CRBN-based PROTACs to achieve selective degradation of a single target while suppressing degradation of CRBN…
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Smart Molecules Targeting Cancer Powerhouse
How can bioorthogonal chemistry and mitochondrial targeting rewrite cancer immunotherapy? By creating enzyme-responsive nanoparticles that self-assemble in tumors and chemically “click”…
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Are Alpha Emiters the Future of Radiotherapy?
While biotech faces a funding downturn, radioligand therapy (RLT) is attracting major investments. The field stands at an important inflection point…
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Let’s Hijack DCAF2 for TPD?!
Well, not quite yet. But maybe soon. Frontier Medicines evaluated E3 ligase DCAF2 (DTL/CDT2), as a novel ligase for targeted protein…
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PROTAC vs Molecular Glue
It doesn’t happen very often to see a direct comparison of a molecular glue degrader and PROTAC, as it has been…
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Introducing mgTag and cTag
How do you study the 90% of proteins that lack small-molecule binding partners? By tagging the protein! The problem is that…
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From DNA Code to Chemistry
Sumon Pratihar, Eric T. Kool and his team from Stanford University just published new paper in ššÆšØš¦šøš¢šÆš„šµš¦ šš©š¦š®šŖš¦, unlocking a new…
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Why Would You Biotinylate Ubiquitin?
E-STUB: A Precision Tool for Mapping E3 Ligase Substrates In march 2025, colleagues from Dana Faber and The Broad Institute published…
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Think spĀ³ Rich!
Top notch medchem building blocks got unlocked. Chemists from Enamine Ltd. published a robust route to saturated azabicyclic scaffolds (Angewandte Chemie):…
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A Unified Platform for Nucleoside Analog Synthesis
Why nucleoside analogs matter and why they’re hard to make Nucleoside analogs (NAs) are among the most successful drug classes in…
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BRET: State-Of-The-Art Technology for Target Engagement in Living Cells
Direct monitoring of a binding interaction between biomolecules and their ligands is one of the cornerstones of early drug discovery, chemical…
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Breakthrough in CrossāCoupling Chemistry
Wang et al. report a new copper-catalyzed methodology for C(spĀ³)-N cross-coupling of unactivated alkyl halides with diverse nucleophiles under thermal conditions…
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Curious How Drug Discovery Can Be Accelerated by DELāML?
Then I would like to invite you to read our paper in RSC Chem. Biol. which also represents my first corresponding…
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Editing Protein Backbone Inside Living Cells
For decades, creating proteins with extended backbones (Ī², Ī³, Ī“-amino acids) inside living cells has been challenging. Researchers at University of…
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Drugging the “Undruggable” š
šø 50 new CRBN neosubstratesšø 3 bona fide degradersšø MS-proteomic platform expanding druggable proteome All of this packed in single paperā…
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Nine New TRIM PRYSPRY Structures Uncover Key Drug Design Challenges
My colleagues from The Structural Genomics Consortium (SGC) (Rezart Zhubi, Andreas C. Joerger, Stefan Knapp) just published a paper “ššš«š®ššš®š«šš„ šš§šš„š²š¬š¢š¬…
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Let it GLOW: Novel Proximity Inducing Modality for DNA Modification
DNA methyltransferases (MTases) can recognize specific DNA sequences and transfer a methyl group from the S-adenosyl-L-methionine (SAM) cofactor to a target…
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Unexpected Organo-Catalysis
Researchers from The Chinese University of Hong Kong discovered an alternative mechanism in which organo-selenium acts as a C-H hydrogen bond…
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Discovery of Small-Molecule Ligands for the E3 Ligase STUB1/CHIP
Finding potent small-molecule E3 ligase binders is notoriously tough. Hereās how teams from AstraZeneca, Pharmaron, and XāChem collaborated to overcome this…
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Group-Transfer Chimeras for Induced Proximity (GRIPs)
Induced proximity is more than ubiquitination and targeted protein degradation. In the recent literature we have seen proximity-inducing modalities for phosphorylation…
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Spiro Spiro Spirocycles Everywhere.
Ā The number of spirocyclic-N-heterocycles has increased dramatically in the recent years. From 10,000 in 2023 ā”ļø 90,000 in 2025 (Substructure search…
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Skeletal Editing Strikes Back!
Imagine a scaffold hopping strategy where you don’t have to re-design your synthetic route for each scaffold. You don’t need Jedi…
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From serendipity to essential protac profiling
The microcosmos of biological processes is complex and full of surprises. This is also the case for a new preprint from…
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Metal-Free CāN coupling via Smiles Rearrangement
Do you like to Smile? Or perhaps youāre a fan of rearrangement reactions like me? If so, youāll want to check…
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CarbonāHeteroatom Cross-Coupling via Red-Light Metallaphotocatalysis
Recently published paper in Nature Communications claims (as the title says): “General method for carbonāheteroatom cross-coupling reactions via semiheterogeneous red-light metallaphotocatalysis”…
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A Biocompatible Lossen Rearrangement inĀ Escherichia Coli
Forget your fume hood, E. coliĀ just became your new reaction vessel š” What’s new?Researchers have shown that a classic organic transformation…
bioconjugation catalysis chemical biology cross-coupling DNA-encoded libraries drug design drug discovery E3 ligase induced proximity medicinal chemistry molecular glue nanotechnology oncology photocatalysis PROTAC reaction mechanism RNA skeletal editing spirocycles targeted protein degradation total synthesis ubiquitin undruggable targets