A5088125942- Protein Degradation and Inhibitors
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Ubiquitin and proteasome pathways
- Microbial Natural Products and Biosynthesis
- Signaling Pathways in Disease
- Marine Sponges and Natural Products
- Semiconductor materials and devices
- Synthetic Organic Chemistry Methods
- Advancements in Semiconductor Devices and Circuit Design
- Multiple Myeloma Research and Treatments
- Peptidase Inhibition and Analysis
- Plant biochemistry and biosynthesis
- Carbohydrate Chemistry and Synthesis
- Genomics, phytochemicals, and oxidative stress
- Cancer, Hypoxia, and Metabolism
- Fungal Biology and Applications
- Nanoplatforms for cancer theranostics
- Phytochemical compounds biological activities
- Plant-derived Lignans Synthesis and Bioactivity
- Photosynthetic Processes and Mechanisms
- Histone Deacetylase Inhibitors Research
- Algal biology and biofuel production
- Ferroptosis and cancer prognosis
- RNA Interference and Gene Delivery
Broad Institute
2023-2025
Novartis (China)
2024
Innovative Genomics Institute
2023
University of California, Berkeley
2019-2023
Harvard University
2023
Novartis (Switzerland)
2020-2021
Berkeley College
2021
Beijing National Laboratory for Molecular Sciences
2017-2018
Peking University
2017-2018
Center for Life Sciences
2017
Abstract Targeted protein degradation (TPD) has emerged as a powerful tool in drug discovery for the perturbation of levels using heterobifunctional small molecules. E3 ligase recruiters remain central to this process yet relatively few have been identified relative ~ 600 predicted human ligases. While, initial utilized non-covalent chemistry binding, very recently covalent engagement novel E3’s proven fruitful TPD application. Herein we demonstrate efficient proteasome-mediated BRD4 by...
Targeted protein degradation (TPD) and proteolysis-targeting chimeras (PROTACs) have arisen as powerful therapeutic modalities for degrading specific proteins in a proteasome-dependent manner. However, major limitation of TPD is the lack E3 ligase recruiters. Recently, we discovered natural product nimbolide covalent recruiter RNF114. Here, show broader utility an applications. We demonstrate that PROTAC linking to kinase BCR-ABL fusion oncogene inhibitor dasatinib, BT1, selectively degrades...
The hallmark of a molecular glue is its ability to induce cooperative protein–protein interactions, leading the formation ternary complex, despite weaker binding toward one or both individual proteins. Notably, extent cooperativity distinguishes glues from bifunctional compounds, which constitute second class inducers interactions. However, apart serendipitous discovery, there have been limited rational screening strategies for high exhibited by glues. Here, we propose binding-based screen...
Abstract Complex natural products are a proven and rich source of disease-modulating drugs efficient tools for the study chemical biology drug discovery. The architectures complex generally considered to represent significant barriers synthesis. Here we describe concise asymmetric synthesis 19-dehydroxyl arisandilactone A—which belongs family architecturally unique, highly oxygenated nortriterpenoids isolated from medicinal plant Schisandra arisanensis . This takes place by means...
Tumor metastasis is the main cause of death in cancer patients. Anoikis resistance one critical malefactor metastatic cells to resist current clinical chemotherapeutic treatments. Although endoperoxide-containing compounds have long been suggested as anticancer drugs, few clinically employed due their instability, complex synthesis procedure or low tumor cell selectivity. Herein, we describe a one-pot strategy synthesize novel amino endoperoxides and derivatives with good yields stabilities....
The stereoselective construction of the CDEFGH ring system lancifodilactone G is described. key steps in this synthesis are (i) ring-closing metathesis for formation oxa-bridged eight-membered ring; (ii) an intramolecular Pauson–Khand reaction sterically congested F and (iii) sequential cross-metathesis, hydrogenation, lactonization reactions installation anomerically stabilized bis-spiro ketal fragment G.
ABSTRACT Molecular glues are small molecules that engage their target and presenter proteins cooperatively. FKBP12 molecular (FK506 rapamycin) were discovered several decades ago have been used clinically, but our understanding of the breadth targets has yet to be fully revealed. To identify novel glues, we constructed screened a multi-million- member non-macrocyclic FKBP12-ligand DNA-encoded library using 25 structurally distinct proteins. Synthesis validation selected hits in biophysical...
Targeted protein degradation (TPD) has emerged as a powerful tool in drug discovery for the perturbation of levels using heterobifunctional small molecules (i.e. PROTACs). E3 ligase recruiters remain central to this process yet relatively few have been identified relative >500 predicted human ligases. While, initial utilized non-covalent chemistry binding, very recently covalent engagement novel E3’s proven fruitful TPD application. Herein we demonstrate efficient proteasome-mediated BRD4...
The hallmark of a molecular glue is its ability to induce cooperative protein-protein interactions, leading the formation ternary complex, despite weaker binding towards one or both individual proteins. Notably, extent cooperativity distinguishes glues from bifunctional compounds, second class inducers interactions. However, apart serendipitous discovery, there have been limited rational screening strategies for high exhibited by glues. Here, we propose binding-based screen DNA-barcoded...
Total synthesis sheds light on biosynthetic relationships among the chlorinated gymnastatin and dankastatin alkaloids.
Abstract Targeted protein degradation (TPD) and proteolysis-targeting chimeras (PROTACs) have arisen as powerful therapeutic modalities for degrading specific targets in a proteasome-dependent manner. However, major limitation to broader TPD applications is the lack of E3 ligase recruiters. Recently, we discovered natural product nimbolide covalent ligand RNF114. When linked BET family inhibitor JQ1, resulting heterobifunctional PROTAC molecule was capable selectively BRD4 cancer cells....
Chlorinated gymnastatin and dankastatin alkaloids derived from the fungal strain Gymnascella dankaliensis have been reported to possess significant anti-cancer activity but their mode of action is unknown. These members electrophilic functional groups that may undergo covalent bond formation with specific proteins exert biological activity. To better understand mechanism this class natural products, we mapped proteome-wide cysteine-reactivity most potent these alkaloids, B, using...
Abstract Chlorinated gymnastatin and dankastatin alkaloids derived from the fungal strain Gymnascella dankaliensis have been reported to possess significant anticancer activity but their mode of action is unknown. These members electrophilic functional groups that can might undergo covalent bond formation with specific proteins exert biological activity. To better understand mechanism this class natural products, we mapped proteome‐wide cysteine reactivity most potent these alkaloids, B, by...
<p>Targeted protein degradation (TPD) has emerged as a powerful tool in drug discovery for the perturbation of levels using heterobifunctional small molecules (i.e. PROTACs). E3 ligase recruiters remain central to this process yet relatively few have been identified relative >500 predicted human ligases. While, initial utilized non-covalent chemistry binding, very recently covalent engagement novel E3’s proven fruitful TPD application. Herein we demonstrate efficient...