A Novel Yeast-Based Platform for Small Molecule Target Deconvolution Reveals Previously Unknown Binding Partners for the Approved Drugs Erlotinib, Atorvastatin, and Sulfasalazine
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Here we provide a personal account of innovation and design principles underpinning a method to interrogate precision electrophile signaling that has come to be known as "REX technologies". This Account is framed in the context of trying to improve methods ...
The discovery of a drug requires over a decade of intensive research and financial investments – and still has a high risk of failure. To reduce this burden, we developed the NICEdrug.ch resource, which incorporates 250,000 bioactive molecules, and studied ...
For several years, drugs with reactive electrophilic appendages have been developed. These units typically confer prolonged residence time of the drugs on their protein targets, and may assist targeting shallow binding sites and/or improving the drug-prote ...
Stereotyped as a nexus of dNTP synthesis, the dual-subunit enzyme - ribonucleotide reductase (RNR) - is coming into view as a paradigm of oligomerization and moonlighting behavior. In the present issue of `omics', we discuss what makes the larger subunit o ...
DNA-protein interactions lie at the crux of life's essential processes. As such, various technologies have been developed to characterize these interactions. The distinct advantages of these technologies can be leveraged to study different facets of these ...
Ribonucleotide reductase (RNR) is an essential enzyme in DNA biogenesis and a target of several chemotherapeutics. Here, we investigate how antileukemic drugs (e.g., clofarabine [CIF]) that target one of the two subunits of RNR, RNR-alpha, affect noncanoni ...
The basic proprotein convertases (PCs) furin, PC1/3, PC2, PC5/6, PACE4, PC4, and PC7 are promising drug targets for human diseases. However, developing selective inhibitors remains challenging due to overlapping substrate recognition motifs and limited str ...
Synthetic protein switches are proteins that can be controlled by an external input, and are useful tools to probe protein function. Antibody fragments and antibody mimetics can be selected to bind, activate, or inhibit several diverse protein targets. Nev ...
Well-validated chemical probes enable testing of biological hypotheses, investigation of target tractability and translatability to the clinical phase. Consequently, these important tool compounds play a key role in the drug discovery process. Moreover, th ...
Libraries of DNA-Encoded small molecules created using combinatorial chemistry and synthetic oligonucleotides are being applied to drug discovery projects across the pharmaceutical industry. The majority of reported projects describe the discovery of rever ...