A5026080428- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Receptor Mechanisms and Signaling
- Analytical Chemistry and Chromatography
- Phagocytosis and Immune Regulation
- Catalytic C–H Functionalization Methods
- Chemical Synthesis and Reactions
- Chemical Synthesis and Analysis
- Radical Photochemical Reactions
- Protein Degradation and Inhibitors
- Neuropeptides and Animal Physiology
- Sulfur-Based Synthesis Techniques
- Peptidase Inhibition and Analysis
- Neuroscience and Neuropharmacology Research
- Monoclonal and Polyclonal Antibodies Research
- Oxidative Organic Chemistry Reactions
- Mass Spectrometry Techniques and Applications
- Ubiquitin and proteasome pathways
- Catalytic Cross-Coupling Reactions
- Hepatitis C virus research
- Synthesis and Catalytic Reactions
- RNA and protein synthesis mechanisms
- Biochemical and Molecular Research
- Histone Deacetylase Inhibitors Research
Icahn School of Medicine at Mount Sinai
2016-2025
Zhongda Hospital Southeast University
2025
Sichuan University
2013-2024
Beijing VDJBio (China)
2024
University of California, San Francisco
2023-2024
Hebei Medical University
2024
Fourth Hospital of Hebei Medical University
2024
Chinese Academy of Medical Sciences & Peking Union Medical College
1995-2023
Chinese Academy of Sciences
2002-2023
University of North Carolina at Chapel Hill
1991-2023
Protein arginine methyltransferases (PRMTs) play a crucial role in variety of biological processes. Overexpression PRMTs has been implicated various human diseases including cancer. Consequently, selective small-molecule inhibitors have pursued by both academia and the pharmaceutical industry as chemical tools for testing therapeutic hypotheses. are divided into three categories: type I which catalyze mono- asymmetric dimethylation residues, II symmetric III PRMT catalyzes only...
Chemogenetic tools such as designer receptors exclusively activated by drugs (DREADDs) are routinely used to modulate neuronal and non-neuronal signaling activity in a relatively noninvasive manner. The first generation of DREADDs were templated from the human muscarinic acetylcholine receptor family insensitive endogenous agonist but instead clozapine-N-oxide (CNO). Despite undisputed success CNO an activator DREADDs, it has been known for some time that is subject low rate metabolic...
Several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have been developed and approved by Food Drug Administration for the treatment of non-small-cell lung cancers, but their efficacy can be compromised acquired drug resistance conferred EGFR-mutant variants. Here, we described discovery a novel E3 ligase von Hippel–Lindau-recruiting EGFR degrader, MS39 (compound 6), first-in-class cereblon-recruiting MS154 10), using proteolysis targeting chimera technology. These...
WDR5-degrader-E3 ligase ternary complex structure–based design led to a highly effective WDR5 degrader with robust in vivo antitumor activities.
Abstract Triple-negative breast cancer (TNBC) is the most aggressive subtype with worst prognosis and few effective therapies. Here we identified MS023, an inhibitor of type I protein arginine methyltransferases (PRMTs), which has antitumor growth activity in TNBC. Pathway analysis TNBC cell lines indicates that activation interferon responses before after MS023 treatment a functional biomarker determinant response, these observations extend to panel human-derived organoids. Inhibition PRMT...
Opioids are some of the most efficacious analgesics used in humans. Prolonged administration opioids, however, often causes development drug tolerance, thus limiting their effectiveness. To explore molecular basis those mechanisms that may contribute to opioid we have isolated a cDNA for human mu receptor, target such narcotics as morphine, codeine, methadone, and fentanyl. The receptor encoded by this is 400 amino acids long with 94% sequence similarity rat receptor. Transient expression...
Natural resistance to infection with unrelated intracellular parasites such as Mycobacteria, Salmonella, and Leishmania is controlled in the mouse by a single gene on chromosome 1, designated Bcg, Ity, or Lsh. A candidate for natural resistance-associated macrophage protein (Nramp), has been isolated shown encode novel macrophage-specific membrane protein, which altered susceptible animals. We have cloned characterized cDNA clones corresponding human NRAMP gene. Nucleotide predicted amino...
The structure of the unligated human T-cell recombinant cyclophilin has been determined at 3 A resolution by multipole isomorphous replacement methods and refined 2.5 to an R factor 0.209. root-mean-square errors bond lengths angles are 0.013 2.8 degrees from ideal geometry, respectively. overall is a beta-barrel, consisting eight antiparallel beta-strands wrapping around barrel surface two alpha-helices sitting on top bottom closing barrel. Inside barrel, seven aromatic other hydrophobic...
We previously reported a potent small molecule Mer tyrosine kinase inhibitor UNC1062. However, its poor PK properties prevented further assessment in vivo. report here the sequential modification of UNC1062 to address DMPK and yield new highly orally bioavailable inhibitor, 11, capable inhibiting phosphorylation vivo, following oral dosing as demonstrated by pharmaco-dynamic (PD) studies examining phospho-Mer leukemic blasts from mouse bone marrow. Kinome profiling versus more than 300...
Metastatic melanoma is one of the most aggressive forms cutaneous cancers. Although recent therapeutic advances have prolonged patient survival, prognosis remains dismal. C-MER proto-oncogene tyrosine kinase (MERTK) a receptor with oncogenic properties that often overexpressed or activated in various malignancies. Using both protein immunohistochemistry and microarray analyses, we demonstrate MERTK expression correlates disease progression. was highest metastatic melanomas, followed by...
Protein methyltransferases (PMTs) comprise a major class of epigenetic regulatory enzymes with therapeutic relevance. Here we present collection chemical probes and associated reagents data to elucidate the function human murine PMTs in cellular studies. Our provides inhibitors antagonists that together modulate most key methylation marks on histones H3 H4, providing an important resource for modulating epigenomes. We describe comprehensive comparative characterization probe respect their...
Mild yet direct: A convenient and efficient method for the synthesis of various aryl ketones by palladium-catalyzed desulfinative addition aromatic sulfinic acid sodium salts to nitriles is described (see scheme). Aromatic aliphatic are successfully reacted with arenesulfinic form in good yields. Detailed facts importance specialist readers published as ”Supporting Information”. Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted authors. Please note:...
A new Wulff-type boronate was designed and synthesized. Upon immobilization on a polymeric monolith acidified as boronic acid, the ligand exhibited specific affinity to cis-diol compounds at medium acidic pH condition.
Multisite phosphorylation is an important and common mechanism for finely regulating protein functions subsequent cellular responses. However, this study largely restricted by the difficulty to capture low-abundance multiply phosphorylated peptides (MPPs) from complex biosamples owing limitation of enrichment materials their interactions with phosphates. Here we show that smart polymer can serve as ideal platform resolve challenge. Driven specific but tunable hydrogen bonding interactions,...
The aberrant expression of protein arginine methyltransferase 5 (PRMT5) has been associated with multiple cancers. Using the proteolysis targeting chimera technology, we discovered a first-in-class PRMT5 degrader 15 (MS4322). Here, report design, synthesis, and characterization compound two structurally similar controls 17 (MS4370) 21 (MS4369), impaired binding to von Hippel-Lindau E3 ligase PRMT5, respectively. Compound 15, but not 21, effectively reduced level in MCF-7 cells. Our mechanism...
The COVID-19 pandemic has clearly brought the healthcare systems worldwide to a breaking point, along with devastating socioeconomic consequences. SARS-CoV-2 virus, which causes disease, uses RNA capping evade human immune system. Nonstructural protein (nsp) 14 is one of 16 nsps in and catalyzes methylation viral at N7-guanosine cap formation process. To discover small-molecule inhibitors nsp14 methyltransferase (MTase) activity, we developed employed radiometric MTase assay screen library...
Transition-metal-catalyzed cross-coupling reactions are a powerful tool to construct carbon–carbon bonds in modern synthetic chemistry. Chromium catalysis is much less developed compared with the widely used palladium and nickel catalysis. Herein, we reported an efficient flexible chromium-catalyzed radical diacylation of alkenes help visible-light photoredox catalysis, giving access valuable 1,4-, 1,6-, 1,7-diones under mild conditions. The utility this methodology was proven by converting...
"CO"n Air: The title reaction was carried out using [PdCl2(PPh3)2] as the catalyst precursor under very mild conditions (balloon pressure of CO and air, at 40→50 °C), produced a wide range aryl carboxyl esters 2 in good to excellent yields. Remarkable selectivity between oxidative carbonylation homocoupling arylboronate 1 also achieved. transition-metal-catalyzed involving gas is fundamental chemical transformation, which not only extends carbon chain length, but introduces synthetically...