A5022852987- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Computational Drug Discovery Methods
- Synthesis and biological activity
- Peptidase Inhibition and Analysis
- PI3K/AKT/mTOR signaling in cancer
- Synthesis and Biological Evaluation
- Cancer therapeutics and mechanisms
- Cancer Immunotherapy and Biomarkers
- Cancer-related Molecular Pathways
- Click Chemistry and Applications
- Cancer Mechanisms and Therapy
- Hippo pathway signaling and YAP/TAZ
- Histone Deacetylase Inhibitors Research
- Bioactive natural compounds
- Chemical Synthesis and Analysis
- Multiple Myeloma Research and Treatments
- Covalent Organic Framework Applications
- Metal-Organic Frameworks: Synthesis and Applications
- Phytochemicals and Antioxidant Activities
- Nanoplatforms for cancer theranostics
- Monoclonal and Polyclonal Antibodies Research
- Cancer, Hypoxia, and Metabolism
- CAR-T cell therapy research
- Quinazolinone synthesis and applications
Zhejiang University
2016-2025
Zhejiang Lab
2020-2025
Second Affiliated Hospital of Zhejiang University
2021-2025
Yangzhou University
2024-2025
Regend Therapeutics (China)
2024
Hangzhou Medical College
2021-2024
Sir Run Run Shaw Hospital
2024
Ministry of Education of the People's Republic of China
2024
Jiangsu University of Technology
2023
Zhejiang Cancer Hospital
2011-2023
Abstract Proteolysis-targeting chimeras (PROTACs), which selectively degrade targeted proteins by the ubiquitin-proteasome system, have emerged as a novel therapeutic technology with potential advantages over traditional inhibition strategies. In past few years, this has achieved substantial progress and two PROTACs been advanced into phase I clinical trials. However, is still maturing design of remains great challenge. order to promote rational PROTACs, we present PROTAC-DB, web-based...
Abstract Medium-sized and medium-bridged rings are attractive structural motifs in natural products therapeutic agents. Due to the unfavourable entropic and/or enthalpic factors with these ring systems, their efficient construction remains a formidable challenge. To address this problem, we herein disclose radical-based approach for diversity-oriented synthesis of various benzannulated carbon- heteroatom-containing 8–11(14)-membered ketone libraries. This strategy involves 1,4- or 1,5-aryl...
Abstract Yes-associated protein (YAP) and its paralog, transcriptional coactivator with PDZ-binding motif (TAZ), play pivotal roles in promoting the progression of hepatocellular carcinoma. However, regulatory mechanism underpinning aberrant activation YAP/TAZ carcinoma remains unclear. In this study, we globally profiled contribution deubiquitinating enzymes (DUB) to both activity abundance models identified ubiquitin-specific peptidase 10 (USP10) as a potent YAP/TAZ-activating DUB....
As the substitute of polybrominated diphenyl ethers (PBDEs), further assessments about potential ecological safety and health risks phosphorus-containing flame retardants (PFRs) are required because worldwide demand for PFRs has been increasing every year. In this study, we examined agonistic/antagonistic activity a group by three in vitro models (luciferase reporter gene assay, yeast two-hybrid E-screen assay). Molecule docking was used to explain interactions between ERα PFRs. Data from...
New functionally diverse urea-derived MOF hydrogen-bond-donating heterogeneous catalysts were achieved via postsynthetic modification, which exhibit excellent catalytic activity and very broad substrate scopes for the Friedel–Crafts alkylation reactions.
The synthesis of new functionally diverse alkenyl-derived Cr-MIL-101s (MIL=material Institute Lavoisier) was realized by a novel and convenient postsynthetic modification (PSM) protocol means the carbon-carbon bond-forming Mizoroki-Heck reaction. PSM demonstrates broad scope substrates with excellent tolerance functionality under mild reaction conditions. Moreover, metal-organic framework (MOF) that bears both alkenyl thiol side chains prepared tandem method has shown adsorbent ability in...
Abstract Immune checkpoint blockade therapies targeting the PD-L1/PD-1 axis have demonstrated clear clinical benefits. Improved understanding of underlying regulatory mechanisms might contribute new insights into immunotherapy. Here, we identify transmembrane and ubiquitin-like domain-containing protein 1 (TMUB1) as a modulator PD-L1 post-translational modifications in tumor cells. Mechanistically, TMUB1 competes with HECT, UBA WWE (HUWE1), E3 ubiquitin ligase, to interact inhibit its...
Bruton's tyrosine kinase proteolysis-targeting chimeras (BTK-PROTACs) have emerged as a promising approach to address the limitations of BTK inhibitors. However, conducting rational discovery orally bioavailable BTK-PROTACs presents significant challenges. In this study, dimensionality reduction analysis and model molecule validation were utilized identify some key structural features for improving oral absorption BTK-PROTACs. The results applied optimize newly discovered B1 B2. Compound C13...
Abstract Antibody-drug conjugates (ADCs) are a class of innovative biopharmaceutical drugs, which, via their antibody (mAb) component, deliver and release potent warhead (a.k.a. payload) at the disease site, thereby simultaneously improving efficacy delivered therapy reducing its off-target toxicity. To design ADCs promising efficacy, it is crucial to have critical data pharma-information biological activities for each ADC. However, no such database has been constructed yet. In this study,...
Abstract Gastric cancer (GC) presents a formidable global health challenge, and conventional therapies face efficacy limitations. Ubiquitin‐specific protease 7 (USP7) plays pivotal roles in GC development, immune response, chemo‐resistance, making it promising target. Various USP7 inhibitors have shown selectivity preclinical studies. However, the mechanistic role of has not been fully elucidated, currently, no approved for clinical use. In this study, DHPO is identified as potent inhibitor...
Abstract Bystander‐killing payloads can significantly overcome the tumor heterogeneity issue and enhance clinical potential of antibody‐drug conjugates (ADC), but rational design identification effective bystander warheads constrain broader implementation this strategy. Here, graph attention networks (GAT) are constructed for a killing scoring model ADC construction workflow first time. To generate efficient bystander‐killing payloads, is utilized score‐directed exatecan derivatives design....
The identification of novel succinate dehydrogenase (SDH) inhibitors represents one the most attractive directions in field fungicide research and development. During our continuous efforts to pursue belonging this class, some structurally pyrazole-furan carboxamide pyrazole-pyrrole derivatives have been discovered via introduction scaffold hopping bioisosterism compound 1, a remarkably potent lead obtained by pharmacophore-based virtual screening. As result evaluation against three...
Abstract Predicting the biological properties of molecules is crucial in computer-aided drug development, yet it’s often impeded by data scarcity and imbalance many practical applications. Existing approaches are based on self-supervised learning or 3D using an increasing number parameters to improve performance. These may not take full advantage established chemical knowledge could inadvertently introduce noise into respective model. In this study, we a more elegant transformer-based...
Succinate dehydrogenase (SDH) has been demonstrated as a promising target for fungicide discovery. Crystal structure data have indicated that the carboxyl "core" of current SDH inhibitors contributed largely to their binding affinity. Thus, identifying novel would remarkably improve biological potency SDHI fungicides. Herein, we report discovery and optimization scaffold inhibitor via integration in silico library design highly specific amide feature-based pharmacophore model. To our...
A mechanistically distinct approach for heterogenizing linear chiral catalysts within the MOF cavities, uniquely featuring a heterogeneous matrix and local homogeneous active domain can exhibit cooperative catalysing capability.