Transcriptional reprogramming through induced proximity has emerged as a powerful strategy for modulating the expression of oncogenic and tumor-suppressive genes. Inspired by transcriptional reprogram...

Heterobifunctional proteolysis-targeting chimeras (PROTACs) have emerged as a powerful strategy to degrade disease-relevant proteins, enabling targeting of previously "undruggable" proteins. Current d...

Reimagining Druggability using Chemoproteomic Platforms - Innovative Genomics Institute (IGI)

Induced proximity modalities encompass monovalent and bifunctional agents, such as molecular glues and proteolysis-targeting chimeras, that induce an interaction between biomolecules to functionally m...

Activity-based protein profiling has identified hundreds of proteins from diverse classes that react at specific cysteine residues with stereochemically defined electrophilic compounds (stereoprobes) ...

Most cancer driving proteins remain undruggable due to the absence of ligandable pockets and their reliance on intrinsically disordered or protein-DNA/protein-protein interactions. Transcription facto...

About the Seminar "Reimagining Druggability using Chemoproteomic Platforms"The Nomura Research Group is focused on reimagining druggability using chemoproteomic platforms to develop transformative med...

Transcription factors are among the most challenging targets for drug discovery due to their lack of classical binding pockets and high degree of intrinsic disorder, despite the therapeutic importance...

While targeted protein degradation is a powerful strategy for eliminating disease-causing proteins, the rational design of monovalent or molecular glue degraders remains challenging. In this study, we...

Preliminary score: ND

FSP1 is an FAD-dependent oxidoreductase that uses NAD(P)H to regenerate the reduced forms of lipophilic quinone antioxidants, such as coenzyme Q10 ...

Nature - Molecular basis of SIFI activity in the integrated stress response

U.S. pharmaceutical companies are increasingly licensing new drugs from China. Former FDA Commissioner Scott Gottlieb explains how to stop the shift.

Targeted protein degradation (TPD) is a powerful strategy for targeting and eliminating disease-causing proteins. While heterobifunctional Proteolysis-Targeting Chimeras (PROTACs) are more modular, th...

The authors report the development of dual covalent proximity inducing molecules capable of selectively cross-linking two non-interacting proteins. Through the selective proximity-based activation of ...

Developing cancer therapies that induce robust death of the malignant cell is critical to prevent relapse. Highly effective strategies, such as immunotherapy, exemplify this observation. Here we provi...

Targeted protein degradation (TPD) is an emergent therapeutic strategy with the potential to circumvent challenges associated with targets unamenable to conventional pharmacological inhibition. Among ...

Targeted protein degradation (TPD) is an emerging therapeutic modality in which small molecules are used to recruit targets to the natural protein degradation machinery of the cell. Molecular glue deg...

Today, the Department of Health and Human Services (HHS), Department of Education (ED), and the U.S. General Services Administration (GSA) announced that through their coordinated efforts they would i...

The proposed approach is expected to save more than $65 million annually.

Studies that touch on LGBT+ health, gender identity and DEI in the biomedical workforce could be terminated, according to documents obtained by Nature.

Development of a paralog-hopping approach leveraging chemical proteomic data on covalently liganded cysteines revealed an allosteric pocket shared by cysteine-containing and cysteine-less paralogous c...

While MYC is a significant oncogenic transcription factor driver of cancer, directly targeting MYC has remained challenging due to its intrinsic disorder and poorly defined structure, deeming it undru...

Policy follows firings of tenure-track scientists and suspension of training programs

Peptide macrocycles are promising therapeutics for a variety of disease indications due to their overall metabolic stability and potential to make highly selective binding interactions with targets. Recent advances in covalent macrocycle peptide discovery, driven by phage and mRNA display methods, have enabled the rapid identification of highly potent and selective molecules from large libraires of diverse macrocycles. However, there are currently limited examples of macrocycles that can be used to disrupt protein–protein interactions and even fewer examples that function by formation of a covalent bond to a target protein. In this work, we describe a directed counter-selection method that enables identification of covalent macrocyclic ligands targeting a protein–protein interaction using a phage display screening platform. This method utilizes binary and ternary screenings of a chemically modified phage display library, employing the stable and weakly reactive aryl fluorosulfate electrophile. We demonstrate the utility of this approach using the SARS-CoV-2 spike-ACE2 protein–protein interaction and identify multiple covalent macrocyclic inhibitors that disrupt this interaction. The resulting compounds displayed antiviral activity against live virus that was irreversible after washout due to the covalent binding mechanism. These results highlight the potential of this screening platform for developing covalent macrocyclic drugs that disrupt protein–protein interactions with long lasting effects.

Pause on posting notices had led to scores of canceled meetings

Invited researchers and academics share and discuss their work at the BE Seminar Series. Our Doctoral students present their research at the Bioengineering & Toxicology Seminars.