A5001631388- Cell death mechanisms and regulation
- HIV/AIDS drug development and treatment
- Click Chemistry and Applications
- Genomics, phytochemicals, and oxidative stress
- HIV Research and Treatment
- Cancer therapeutics and mechanisms
- Pneumocystis jirovecii pneumonia detection and treatment
- Synthesis and biological activity
- Cancer-related Molecular Pathways
- Marine Sponges and Natural Products
- Microbial Natural Products and Biosynthesis
- Bioactive Compounds and Antitumor Agents
- Synthesis and Biological Evaluation
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Chemical Synthesis and Analysis
- Lung Cancer Research Studies
- Immune Response and Inflammation
- Carbohydrate Chemistry and Synthesis
- interferon and immune responses
- Computational Drug Discovery Methods
- Natural Antidiabetic Agents Studies
- Mitochondrial Function and Pathology
- Protein Degradation and Inhibitors
- Garlic and Onion Studies
Second Military Medical University
2016-2025
Ningxia Medical University
2018-2025
Guangdong Pharmaceutical University
2024-2025
Tongji University
2021-2024
Shanghai Tenth People's Hospital
2021-2024
Fudan University
2019-2023
Yinchuan First People's Hospital
2021
University of Minnesota
2014-2016
The inhibition of porcine pancreatic α-amylase and mammalian α-glucosidase by 16 individual flavonoids was determined. IC50 values for baicalein, (+)-catechin, quercetin, luteolin were 74.1 ± 5.6, 175.1 9.1, 281.2 19.2, 339.4 16.3 μM, respectively, against α-glucosidase. apigenin baicalein 146.8 7.1 446.4 23.9 α-amylase. combination or with acarbose showed synergistic inhibition, the (+)-catechin antagonistic additive at lower concentrations a higher concentration. Kinetic studies activity...
In this study, rapid structure-based virtual screening and hit-based substructure search were utilized to identify small molecules that disrupt the interaction of Keap1-Nrf2. Special emphasis was placed toward maximizing exploration chemical diversity initial hits while economically establishing informative structure-activity relationship (SAR) novel scaffolds. Our most potent noncovalent inhibitor exhibits three times improved cellular activation in Nrf2 than active Keap1 known date.
The p53-MDM2 interaction has been proved to be a valuable target develop effective antitumor agents. Novel inhibitors bearing pyrrolidone scaffolds were successfully identified by structure-based design. nanomolar inhibitor 5 possessed good inhibitory activity (K(i) = 780 nM) due its hydrophobic and hydrogen bonding interactions with MDM2. Further hit optimization led the discovery of number highly potent derivatives improved in vitro antiproliferative potency. Compounds 41 260.0 60a 150.0...
The Keap1-Nrf2 pathway has been established as a therapeutic target for Alzheimer's disease (AD). Directly inhibiting the protein-protein interaction (PPI) between Keap1 and Nrf2 reported an effective strategy treating AD. Our group validated this in AD mouse model first time using inhibitor 1,4-diaminonaphthalene NXPZ-2 with high concentrations. In present study, we new phosphodiester containing diaminonaphthalene compound, POZL, designed to PPI interface structure-based design combat...
Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist with favorable effects on fatty and glucose metabolism, has been considered the leading candidate drug for nonalcoholic steatohepatitis (NASH) treatment. However, its limited effectiveness in resolving liver fibrosis lipotoxicity-induced cell death remains major drawback. Ferroptosis, newly recognized form of characterized by uncontrolled lipid peroxidation, is involved progression NASH. Nitric oxide (NO) versatile biological...
Directly blocking the Keap1–Nrf2 pathway is a promising strategy for mitigation of acute lung injury (ALI). Peptide inhibitors have been reported to high Keap1 binding affinity. However, these showed weak activity in cells and/or animals. In this study, we designed series linear peptides from an Nrf2-based 9-mer Ac-LDEETGEFL-NH2. To improve cellular activity, further cyclic based on crystal complex with peptide. Among them, ZC9 targeting better affinity (KD2 = 51 nM). Specifically, it...
Receptor-interacting protein (RIP) kinase 1 is involved in immune-mediated inflammatory diseases including ulcerative colitis (UC) by regulating necroptosis and inflammation. Our group previously identified TAK-632 (5) as an effective inhibitor dual-targeting RIP1 RIP3. In this study, using ligand-based substituent-anchoring design strategy, we focused on the benzothiazole ring to obtain a series of analogues showing significantly improving anti-necroptosis activity selectivity over Among...
Oxidative stress plays a vital role in the development of cerebral ischemic/reperfusion (I/R). Targeting oxidative is proposed to be an effective strategy treat I/R injury. Gentiana macrophylla Pall reported have potential protective effect against stroke. Swertiamarin (Swe), active secoiridoid glycoside compound isolated from Pall, has been possess antioxidative potential. This study explore whether Swe could prevent brain injury, and related mechanisms are also elucidated using mice middle...
A new Keap1-Nrf2 protein-protein interaction (PPI) inhibitor ZJ01 was identified from our compound library by fluorescence polarization assay, surface plasmon resonance, molecular docking and dynamics simulation. could in vitro trigger Nrf2 nuclear translocation, subsequently resulting increased mRNA levels of target genes HO-1 NQO1. Meanwhile, suppressed LPS-induced production ROS the pro-inflammatory cytokines TNF-α, IL-1β IL-6 H9c2 cardiac cells. Moreover, an vivo mouse model septic...
Two new biscembranoid-like compounds, bissubvilides A (1) and B (2), were isolated together with sarsolilide (3), the proposed biogenetic precursor to 1, from soft coral Sarcophyton subviride. The structures absolute configurations solved by spectroscopic analysis TDDFT/ECD DFT/NMR calculations. represent a novel skeleton presumed derive cembrane-type diene capnosane-type dienophile via Diels–Alder reaction. These two molecules exerted no cytotoxicity against MG-63 or A549 tumor cells HuH7...
Background and Purpose Necroptosis is a form of programmed, caspase‐independent, cell death, mediated by receptor‐interacting protein kinases, RIPK1 RIPK3, the mixed lineage kinase domain‐like (MLKL). contributes to pathophysiology various inflammatory, infectious, degenerative diseases. Thus, identification low MW inhibitors for necroptosis has broad therapeutic relevance. Here, we identified that pan‐Raf inhibitor TAK‐632 was also an necroptosis. We have further generated more selective,...