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How can bioorthogonal chemistry and mitochondrial targeting rewrite cancer immunotherapy? By creating enzyme-responsive nanoparticles that self-assemble in tumors and chemically “click” with an arsenic payload, scientists achieved complete tumor eradication and durable immune memory. Two main components – two small molecules (Fig. panel b)💊 𝐏𝐫𝐨𝐛𝐞 𝐏-𝐓𝐂𝐎-𝐓𝐏𝐏:An ALP-responsive small molecule comprising a phosphate-caged fluorophore (mCy), a…

While biotech faces a funding downturn, radioligand therapy (RLT) is attracting major investments. The field stands at an important inflection point as next-generation alpha-emitting therapies prepare for phase 3 readouts in 2026. Why investors are betting on RLTs✔️ Imaging-guided development enables visualization before treatment✔️ Physical, rather than pharmacological, cancer-killing mechanism✔️ Unprecedented speed: candidate selection to…

Well, not quite yet. But maybe soon. Frontier Medicines evaluated E3 ligase DCAF2 (DTL/CDT2), as a novel ligase for targeted protein degradation by PROTACs (published in 𝘚𝘵𝘳𝘶𝘤𝘵𝘶𝘳𝘦): “𝘚𝘵𝘳𝘶𝘤𝘵𝘶𝘳𝘢𝘭 𝘣𝘢𝘴𝘪𝘴 𝘧𝘰𝘳 𝘋𝘊𝘈𝘍2 𝘢𝘴 𝘢 𝘯𝘰𝘷𝘦𝘭 𝘌3 𝘭𝘪𝘨𝘢𝘴𝘦 𝘧𝘰𝘳 𝘗𝘙𝘖𝘛𝘈𝘊-𝘮𝘦𝘥𝘪𝘢𝘵𝘦𝘥 𝘵𝘢𝘳𝘨𝘦𝘵𝘦𝘥 𝘱𝘳𝘰𝘵𝘦𝘪𝘯 𝘥𝘦𝘨𝘳𝘢𝘥𝘢𝘵𝘪𝘰𝘯” Why it is important✅ This work addresses a key limitation in PROTAC development: the…

It doesn’t happen very often to see a direct comparison of a molecular glue degrader and PROTAC, as it has been just published in J Med Chem: “𝘋𝘪𝘴𝘤𝘰𝘷𝘦𝘳𝘺 𝘰𝘧 𝘢 𝘚𝘦𝘭𝘦𝘤𝘵𝘪𝘷𝘦 𝘢𝘯𝘥 𝘗𝘰𝘵𝘦𝘯𝘵 𝘉𝘊𝘓6 𝘗𝘙𝘖𝘛𝘈𝘊 𝘸𝘪𝘵𝘩 𝘌𝘧𝘧𝘪𝘤𝘢𝘤𝘪𝘰𝘶𝘴 𝘈𝘯𝘵𝘪𝘱𝘳𝘰𝘭𝘪𝘧𝘦𝘳𝘢𝘵𝘪𝘷𝘦 𝘈𝘤𝘵𝘪𝘷𝘪𝘵𝘺 𝘧𝘰𝘳 𝘵𝘩𝘦 𝘛𝘳𝘦𝘢𝘵𝘮𝘦𝘯𝘵 𝘰𝘧 𝘋𝘪𝘧𝘧𝘶𝘴𝘦 𝘓𝘢𝘳𝘨𝘦 𝘉‑𝘊𝘦𝘭𝘭 𝘓𝘺𝘮𝘱𝘩𝘰𝘮𝘢” Why it is interesting✔️ Glue degraders as well…

How do you study the 90% of proteins that lack small-molecule binding partners? By tagging the protein! The problem is that most tags are too bulky, like trying to study a butterfly 🦋 with a bowling ball attached. To address this limitation, researchers at the Broad Institute developed two novel protein tags which were published…

Sumon Pratihar, Eric T. Kool and his team from Stanford University just published new paper in 𝘈𝘯𝘨𝘦𝘸𝘢𝘯𝘥𝘵𝘦 𝘊𝘩𝘦𝘮𝘪𝘦, unlocking a new way of selective RNA modification: “𝘚𝘦𝘲𝘶𝘦𝘯𝘤𝘦-𝘚𝘱𝘦𝘤𝘪𝘧𝘪𝘤 𝘐𝘯𝘴𝘵𝘢𝘭𝘭𝘢𝘵𝘪𝘰𝘯 𝘰𝘧 𝘈𝘳𝘺𝘭 𝘎𝘳𝘰𝘶𝘱𝘴 𝘪𝘯 𝘙𝘕𝘈 𝘷𝘪𝘢 𝘋𝘕𝘈-𝘊𝘢𝘵𝘢𝘭𝘺𝘴𝘵 𝘊𝘰𝘯𝘫𝘶𝘨𝘢𝘵𝘦𝘴” Key innovationDNA-directed approach that utilizes a DNA oligonucleotide carrying a nucleophilic amine to promote site-selective SNAr reaction at RNA…

E-STUB: A Precision Tool for Mapping E3 Ligase Substrates In march 2025, colleagues from Dana Faber and The Broad Institute published in 𝘕𝘢𝘵𝘶𝘳𝘦 𝘊𝘩𝘦𝘮𝘪𝘤𝘢𝘭 𝘉𝘪𝘰𝘭𝘰𝘨𝘺: “𝘜𝘣𝘪𝘲𝘶𝘪𝘵𝘪𝘯-𝘴𝘱𝘦𝘤𝘪𝘧𝘪𝘤 𝘱𝘳𝘰𝘹𝘪𝘮𝘪𝘵𝘺 𝘭𝘢𝘣𝘦𝘭𝘪𝘯𝘨 𝘧𝘰𝘳 𝘵𝘩𝘦 𝘪𝘥𝘦𝘯𝘵𝘪𝘧𝘪𝘤𝘢𝘵𝘪𝘰𝘯 𝘰𝘧 𝘌3 𝘭𝘪𝘨𝘢𝘴𝘦 𝘴𝘶𝘣𝘴𝘵𝘳𝘢𝘵𝘦𝘴” How it worksE-STUB (E3-Substrate Tagging by Ubiquitin Biotinylation) combines the principles of proximity labeling with the functional specificity of ubiquitin…

Top notch medchem building blocks got unlocked. Chemists from Enamine Ltd. published a robust route to saturated azabicyclic scaffolds (Angewandte Chemie): “𝘉𝘪𝘤𝘺𝘤𝘭𝘪𝘤 𝘐𝘴𝘰𝘴𝘵𝘦𝘳𝘦𝘴 𝘰𝘧 𝘗𝘺𝘳𝘪𝘥𝘪𝘯𝘦/𝘗𝘪𝘱𝘦𝘳𝘪𝘥𝘪𝘯𝘦: 𝘍𝘳𝘰𝘮 𝘚𝘺𝘯𝘵𝘩𝘦𝘴𝘪𝘴 𝘵𝘰 𝘈𝘱𝘱𝘭𝘪𝘤𝘢𝘵𝘪𝘰𝘯𝘴” Key innovationKOtBu/I₂/CO₂-mediated cyclization of cyclic alkenyl amines, delivering:✔️ 2-azabicyclo[2.2.2]octanes (35-73% yield)✔️ 2-azabicyclo[3.2.1]octane (69% yield)✔️ 2-azabicyclo[2.2.1]heptanes (75-85% yield)✔️ 7-azabicyclo[2.2.1]heptane (70% yield)✔️ 2-azabicyclo[3.1.1]heptanes (62-73% yield)✔️ 2-azabicyclo[2.1.1]hexanes (52-90% yield) ✅ 52–90% yield✅ Scales up to…

Why nucleoside analogs matter and why they’re hard to make Nucleoside analogs (NAs) are among the most successful drug classes in medicine, with more than 30 currently approved for treating viral infections such as HIV/AIDS and hepatitis, as well as certain cancers. These synthetic mimics of natural nucleosides act as antimetabolites through diverse mechanisms: inhibiting…

Direct monitoring of a binding interaction between biomolecules and their ligands is one of the cornerstones of early drug discovery, chemical biology and related disciplines. Assays that allow (semi)-quantitative measurements of the direct binding event, so-called target engagement (TE), became indispensable components of workflows for development or characterization of small molecules, peptides, antibodies, oligonucleotides and…