A5080361774- Synthesis and biological activity
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Biochemical and Molecular Research
- Cancer therapeutics and mechanisms
- Tuberculosis Research and Epidemiology
- Peptidase Inhibition and Analysis
- Crystal structures of chemical compounds
- Chemical Synthesis and Analysis
- Ubiquitin and proteasome pathways
- HIV/AIDS drug development and treatment
- Quinazolinone synthesis and applications
- Antimicrobial Peptides and Activities
- Cancer, Hypoxia, and Metabolism
- Antibiotic Resistance in Bacteria
- Synthesis and Biological Evaluation
- Cytokine Signaling Pathways and Interactions
- Phenothiazines and Benzothiazines Synthesis and Activities
- Protein Degradation and Inhibitors
- Pneumocystis jirovecii pneumonia detection and treatment
- Bioactive Compounds and Antitumor Agents
- Click Chemistry and Applications
- Oral microbiology and periodontitis research
- Computational Drug Discovery Methods
- Endoplasmic Reticulum Stress and Disease
Sichuan University
2016-2025
State Key Laboratory of Biotherapy
2015-2024
West China Hospital of Sichuan University
2021
West China Medical Center of Sichuan University
2014-2019
Chengdu University
2014-2019
Fudan University
2002-2003
University of Washington
1995-1997
Jiangxi University of Traditional Chinese Medicine
1991
The activation of Homo sapiens Casein lysing protease P (HsClpP) by a chemical or genetic strategy has been proved to be new potential therapy in acute myeloid leukemia (AML). However, limited efficacy achieved with classic agonist imipridone ONC201. Here, novel class HsClpP agonists is designed and synthesized using ring-opening based on the lead compound 1 reported our previous study. Among these scaffold agonists, 7k exhibited remarkably enhanced proteolytic activity (EC50 = 0.79 ± 0.03...
Human dihydroorotate dehydrogenase (hDHODH) is an attractive target for cancer therapy. Based on its crystal structure, we designed and synthesized a focused compound library containing the structural moiety of 1,4-benzoquinone, which possesses reactive oxygen species (ROS) induction capacity. Compound 3s with naphtho[2,3-d][1,2,3]triazole-4,9-dione scaffold exhibited inhibitory activity against hDHODH. Further optimization led to compounds 11k 11l, inhibited hDHODH IC50 values 9 4.5 nM,...
Homo sapiens caseinolytic protease P (HsClpP) plays an important role in maintaining mitochondrial proteostasis. Activating HsClpP has been proved to be a potential strategy for cancer therapy. In this paper, novel class of agonists is designed and synthesized using position shift based on the imipridone ONC201. Among these newly derivatives, compound 16z exhibits remarkably enhanced antitumor activity (IC50 = 0.04 μM against HCT116 cells). It can improve thermal stability induce...
Homo sapiens caseinolytic protease P (HsClpP) activation is a promising strategy for colon cancer treatment. In this study, CCG1423 was identified as selective activator of HsClpP. After optimization, NCA029 emerged the most potent compound, with an EC50 0.2 μM against Molecular dynamics revealed that affinity YYW aromatic network crucial its selectivity toward Furthermore, displayed favorable pharmacokinetics and safety profiles significantly inhibited tumor growth in HCT116 xenografts,...
Chemical agonism of human caseinolytic protease P (HsClpP) is increasingly being recognized as a potential anticancer strategy due to its critical role in maintaining mitochondrial homeostasis. We unveil the discovery 5-(piperidin-4-yl)-1,2,4-oxadiazole derivatives novel class HsClpP agonists and demonstrate for first time application treatment hepatocellular carcinoma (HCC) (Pace, A.; Pierro, P. The new era 1,2,4-oxadiazoles. Org. Biomol. Chem. 2009, 7 (21), 4337-4348). Compound SL44...
A large amount of evidence suggests that monocytes/macrophages infiltration is implicated in a variety inflammatory diseases including acute liver injury. Monocyte chemoattractant protein 1 (MCP-1) plays crucial role the process macrophages recruitment. We herein presented small-molecule library and feasible quick screening method evaluating potency inhibition chemotaxis RAW264.7 cells stimulated by MCP-1. Fifty-three small molecules were synthesized screened, four compounds (2g, 2h, 4f, 6h)...
Traditional antibody-drug conjugates (ADCs) mainly suppress tumor growth through either chemotherapy with cytotoxic payloads or immunotherapy immuno-modulators. However, a single therapeutic modality may limit their exploration. Herein, we developed new type of drug conjugate termed CAR-EDC (CAR-M-derived exosome-drug conjugate) by using CAR-exosomes from CAR-M cells as the targeting carrier that contains high level CXCL10. could significantly enhance immunological activation and migratory...