A5017839503- Protein Degradation and Inhibitors
- Click Chemistry and Applications
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Fibroblast Growth Factor Research
- Alzheimer's disease research and treatments
- Advanced Glycation End Products research
- Multiple Myeloma Research and Treatments
- Chemical Synthesis and Analysis
- Computational Drug Discovery Methods
- Protein Kinase Regulation and GTPase Signaling
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Biochemical effects in animals
- Histone Deacetylase Inhibitors Research
- Cholinesterase and Neurodegenerative Diseases
- HIV Research and Treatment
- Chronic Lymphocytic Leukemia Research
- Melanoma and MAPK Pathways
University of California, Berkeley
2020-2023
Innovative Genomics Institute
2021-2022
Dana-Farber Cancer Institute
2020-2022
Harvard University
2020-2022
Novartis (Switzerland)
2021
Middlebury College
2017-2020
Proteolysis-targeting chimeras (PROTACs), heterobifunctional compounds that consist of protein-targeting ligands linked to an E3 ligase recruiter, have arisen as a powerful therapeutic modality for targeted protein degradation (TPD). Despite the popularity TPD approaches in drug discovery, only small number recruiters are available >600 ligases exist human cells. Here, we discovered cysteine-reactive covalent ligand, EN106, targets FEM1B, recently critical component cellular response...
Abstract Aberrant activation of FGFR signaling occurs in many cancers, and ATP‐competitive inhibitors have received regulatory approval. Despite demonstrating clinical efficacy, these exhibit dose‐limiting toxicity, potentially due to a lack selectivity amongst the family are poorly tolerated. Here, we report discovery characterization DGY‐09‐192, bivalent degrader that couples pan‐FGFR inhibitor BGJ398 CRL2 VHL E3 ligase recruiting ligand, which preferentially induces FGFR1&2...
While vaccines and antivirals are now being deployed for the current SARS-CoV-2 pandemic, we require additional antiviral therapeutics to not only effectively combat its variants, but also future coronaviruses. All coronaviruses have relatively similar genomes that provide a potential exploitable opening develop therapies will be effective against all Among various genes proteins encoded by coronaviruses, one particularly "druggable" or easy-to-drug target is coronavirus Main Protease...
SRC is a major regulator of many signaling pathways and contributes to cancer development. However, development selective inhibitor has been challenging, FDA-approved inhibitors, dasatinib bosutinib, are multitargeted kinase inhibitors. Here, we describe our efforts develop covalent by targeting cysteine 277 on the P-loop SRC. Using promiscuous (CKI) SM1-71 as starting point, developed 15a, which discriminates from other targets including TAK1 FGFR1. As an irreversible inhibitor, compound...
Unregulated Src activity promotes malignant processes in cancer, but no Src-directed targeted therapies are used clinically, possibly because early inhibitors produce off-target effects leading to toxicity. Improved selective may enable therapies. Previously, we reported an irreversible inhibitor, DGY-06-116, based on the hybridization of dasatinb and a promiscuous covalent kinase probe SM1-71. Here, report biochemical biophysical characterization this compound. An x-ray co-crystal structure...
Abstract Targeted protein degradation is a powerful therapeutic modality that uses heterobifunctional small-molecules to induce proximity between E3 ubiquitin ligases and target proteins ubiquitinate degrade specific of interest. However, many are ubiquitinated degraded drive disease pathology; in these cases targeted stabilization (TPS), rather than degradation, the actively using small-molecule would be therapeutically beneficial. Here, we present Deubiquitinase-Targeting Chimera (DUBTAC)...
Abstract Proteolysis Targeting Chimeras (PROTACs), heterobifunctional compounds that consist of protein-targeting ligands linked to an E3 ligase recruiter, have arisen as a powerful therapeutic modality for targeted protein degradation (TPD). Despite the popularity TPD approaches in drug discovery, only small number recruiters are available >600 ligases exist human cells. Here, we discovered cysteine-reactive covalent ligand, EN106, targets FEM1B, recently critical component cellular...
Abstract While vaccines and antivirals are now being deployed for the current SARS-CoV-2 pandemic, we require additional antiviral therapeutics to not only effectively combat its variants, but also future coronaviruses. All coronaviruses have relatively similar genomes that provide a potential exploitable opening develop therapies will be effective against all Among various genes proteins encoded by coronaviruses, one particularly “druggable” or easy-to-drug target is coronavirus Main...
Abstract Aberrant activation of FGFR signaling occurs in many cancers, and ATP‐competitive inhibitors have received regulatory approval. Despite demonstrating clinical efficacy, these exhibit dose‐limiting toxicity, potentially due to a lack selectivity amongst the family are poorly tolerated. Here, we report discovery characterization DGY‐09‐192, bivalent degrader that couples pan‐FGFR inhibitor BGJ398 CRL2 VHL E3 ligase recruiting ligand, which preferentially induces FGFR1&2...