Nathanael S. Gray

This paper develops covalent EGFR inhibitors targeting cysteine 775 and 797, showing improved efficacy and resistance delay in osimertinib-resistant models.

This paper designs a new proximity labeling enzyme, FlexID, using computational methods to improve spatial precision and versatility for mapping protein interactions and proteomes.

This paper introduces ratiometric transcriptional activation to detect protein abundance changes by converting protein degradation into gene expression outputs in live cells.

This paper develops KAT-TCIPs to induce cell death in diffuse large B cell lymphoma by redirecting p300 and CBP to activate programmed cell death genes repressed by BCL6.

This paper develops a small molecule, TRAP-1, that activates mutant p53 by forming a ternary complex with BRD4, leading to p53 target gene upregulation and inhibition of cancer cell growth.

The paper discovers a charged molecular glue, c-Glue, through targeted degron display, enabling the development of Molecular Glue Degraders (MGDs) for protein degradation.

This paper identifies a druggable redox switch on SHP1 that controls macrophage inflammation by developing a covalent agonist targeting a specific cysteine residue.

This study identifies a PTER inhibitor that reduces food intake and body weight in mice, linking PTER function to obesity treatment.

The paper identifies inhibitor-induced kinase destabilization as a common phenomenon and reveals that it occurs through endogenous proteolytic mechanisms rather than classical ubiquitination.

This paper introduces DD-CIPs, bivalent molecules that induce DNA damage response and apoptosis in cancer cells, showing efficacy against PARPi-resistant cancers.

This paper develops chemical probes for FBXO22, including a degrader and a recruitment ligand, to enable targeted protein degradation applications.

The paper identifies 298 protein targets of CRBN-binding molecular glues using a high-throughput affinity purification mass spectrometry workflow and demonstrates a lead compound for the new target PPIL4.

This study develops a bivalent small molecule, EB-TCIP, that relocalizes EWS/FLI1 to induce BCL6 target genes, demonstrating a strategy to target fusion oncoproteins in Ewing sarcoma.

This study shows CDK12/13 inhibition disrupts nucleolar structure and causes aberrant IGS rRNA transcript expression due to impaired processing and degradation.

This study develops potent and selective CK1α molecular glue degraders through scaffold hopping and structure-activity relationship analysis of a glutarimide-based library.

The paper identifies CRBN-dependent WEE1 molecular glue degraders through combinatorial library screening and medicinal chemistry, providing structural insights into kinase selectivity.

The paper develops bivalent molecules that convert kinase inhibitors into activators of proapoptotic genes, achieving selective killing of DLBCL cells with low cytotoxicity.

This study develops electrophilic degraders using SNAr chemistry, enabling selective protein degradation without requiring a defined E3 ligase recruiter.

This study evaluates how electrophilic modifications to JQ1 affect DCAF16 trans-labeling and BRD4 degradation, showing a correlation between warhead exposure and degradation efficiency.

This study develops small molecule degraders of the dengue virus envelope protein, demonstrating their ability to induce proteosome-mediated degradation and providing a foundation for antiviral drug development.

This study shows that down-regulating AKT proteins slows mutant-KRAS pancreatic tumor growth more effectively than inhibiting AKT kinase activity.

The paper describes a method to control CRISPR/Cas9 activity using proteasomal degradation of an anti-CRISPR protein fused to a degradation or shutoff tag.

The paper identifies a PP2A-Integrator complex that opposes CDK9 activity to regulate transcription and shows its therapeutic synergy in leukemia.

The paper develops tools to compare and design optimized small molecule libraries using chemical and biological data, resulting in a more effective kinase inhibitor library.

The paper introduces the L1000 platform, a high-throughput gene expression profiling method, and reports 1.3 million perturbational profiles expanding the Connectivity Map for drug mechanism discovery and functional annotation.