A5073332881- Cancer, Hypoxia, and Metabolism
- Sirtuins and Resveratrol in Medicine
- Pharmacogenetics and Drug Metabolism
- Traditional Chinese Medicine Analysis
- Liver Disease Diagnosis and Treatment
- Metabolomics and Mass Spectrometry Studies
- Cancer therapeutics and mechanisms
- Drug Transport and Resistance Mechanisms
- Nanoparticle-Based Drug Delivery
- Protein Degradation and Inhibitors
- Lipid metabolism and biosynthesis
- Ginseng Biological Effects and Applications
- Cancer Treatment and Pharmacology
- Neurological Disease Mechanisms and Treatments
- Pharmacological Effects of Natural Compounds
- Metabolism, Diabetes, and Cancer
- Diet, Metabolism, and Disease
- Antiplatelet Therapy and Cardiovascular Diseases
- Ubiquitin and proteasome pathways
- Lung Cancer Research Studies
- Natural Products and Biological Research
- Synthesis and bioactivity of alkaloids
- Epigenetics and DNA Methylation
- Cytokine Signaling Pathways and Interactions
- Lung Cancer Treatments and Mutations
China Pharmaceutical University
2016-2025
Chang'an University
2021-2023
State Key Laboratory of Natural Medicine
2021-2023
PharmacoGenetics (China)
2013
The global spread of multidrug-resistant pathogenic fungi presents a serious threat to human health, necessitating the discovery antifungals with unique modes action1. However, conventional activity-based screening for previously undescribed antibiotics has been hampered by high-frequency rediscovery known compounds and lack new antifungal targets2. Here we report polyene antibiotic, mandimycin, using phylogeny-guided natural-product platform. Mandimycin is biosynthesized mand gene cluster,...
Alanine-serine-cysteine transporter 2 (ASCT2) is up-regulated in lung cancers, and inhibiting it could potentially lead to nutrient deprivation, making a viable strategy for cancer treatment. In this study, we present series of ASCT2 inhibitors based on aminobutanoic acids, which exhibit potent inhibitory activity. Two compounds, 20k 25e, were identified as novel inhibitors, with IC50 values at the micromolar level both A549 HEK293 cells, effectively blocking glutamine (Gln) uptake....
Background and Purpose Hypoxic activation of hypoxia‐inducible factor 1α (HIF‐1α) fibrosis in adipose tissue contribute to dysfunction. This study was designed investigate the effects metformin resveratrol on regulation HIF‐1α hypoxic tissue. Experimental Approach Mice were fed a high‐fat diet induce hypoxia tissue; incubated vitro 1% O 2 showed similar change. The hypoxia, accumulation, endoplasmic reticulum stress gene expressions extracellular matrix components pro‐inflammatory cytokines...
In recent years, berberine has increasingly become a topic of research as treatment for diabetes due to its repair function, which recovers damaged pancreatic β cells. However, it is the complications that seriously affect patients’ life quality and longevity, among diabetic neuropathy consequent acute pain are most common. this study, we established STZ-induced models observe whether berberine, main constitute Coptis chinensis Franch shown good hypoglycemic effects, could relieve...
Effectiveness of epidermal growth factor receptor (EGFR) inhibitors, including Osimertinib, for treating non-small-cell lung cancer (NSCLC) is limited due to the continuous emergence drug resistance. Hence, it urgent develop new therapeutic approaches. CDK9, a key regulator RNA transcription, has emerged as promising target development antitumor drugs its crucial role in modulating levels antiapoptotic protein Mcl-1. Herein, we present synthesis, optimization, and evaluation selective CDK9...
Osteoarthritis is the most common joint disorder. However, there are no disease-modifying drugs approved for OA treatment. CDC2-like kinase 2 (CLK2) could modulate Wnt signaling via alternative splicing of target genes and further affect bone differentiation, chondrocyte function, inflammation, making CLK2 an attractive therapy. In this study, we designed synthesized a series highly potent inhibitors based on Indazole 1. Among them, compound LQ23 showed more elevated inhibitory activity...
Molecular glue degraders induce "undruggable" protein degradation by a proximity-induced effect. Inspired the clinical success of immunomodulatory drugs, we aimed to design novel molecular targeting GSPT1. Here, report series GSPT1 degraders. LYG-409, 2H-chromene derivative, was identified as potent, selective, and orally bioavailable degrader with excellent antitumor activity in vivo (anti-Acute Myeloid Leukemia MV4–11 xenograft model: TGI = 94.34% at 30 mg/kg; prostate cancer 22Rv1 104.49%...
The inhibition of glutaminase 1 (GLS1) represents a potential treatment malignant tumors. Structural analysis led to the design novel series macrocyclic GLS1 allosteric inhibitors. Through extensive structure–activity relationship studies, promising candidate molecule 13b (LL202) was identified with robust inhibitory activity (IC50 = 6 nM) and high binding affinity (SPR, Kd 24 nM; ITC, 37 nM). X-ray crystal structure 13b–GLS1 complex resolved, revealing unique mode providing structural...
Upregulated de novo lipogenesis (DNL) plays a pivotal role in the progress of nonalcoholic fatty liver disease (NAFLD). Cytoplasmic citrate flux, mediated by plasma membrane transporter (SLC13A5), mitochondrial carrier (SLC25A1), and ATP-dependent lyase (ACLY), determines central carbon source for acetyl-CoA required DNL. Curcumin, widely accepted dietary polyphenol, can attenuate lipid accumulation NAFLD. Here, we first investigated lipid-lowering effect curcumin against NAFLD oleic...
Huoxuezhitong capsule (HXZT, activating blood circulation and relieving pain capsule), has been applied for osteoarthritis since 1974. It consists of Angelica sinensis (Oliv.) Diels, Panax notoginseng (Burkill) F. H. Chen ex C. H., Boswellia sacra, Borneol, Eupolyphaga Walker, Pyritum. However, the direct effects HXZT on underlying mechanisms were poorly understood. In this study, we aimed to explore analgesia effect MIA-induced rat mechanisms. The anti-inflammatory in vivo tested by...
Ubiquitin-specific protease 8 (USP8), belonging to the deubiquitinase family, has been implicated be closely related occurrence of many malignant tumors, but only a few USP8-targeting inhibitors have reported date. In this study, we present virtual screening discover novel hit candidates that inhibit catalytic activity USP8. Exploration structure–activity relationship led identification compound DC-U4106, which binds USP8 with KD value 4.7 μM and is selective over USP2 USP7. Western blotting...
Aldo-keto reductase 1C3 (AKR1C3) is correlated with tumor development and chemotherapy resistance. The catalytic activity of the enzyme has been recognized as one important factors in inducing anthracycline (ANT) resistance cancer cells. Inhibition AKR1C3 may provide a promising approach to restore chemosensitivity ANT-resistant cancers. Herein, series biaryl-containing inhibitors developed. best analogue S07-1066 selectively blocked AKR1C3-mediated reduction doxorubicin (DOX) MCF-7...
Lipusu is the first paclitaxel liposome preparation approved in world and has been widely used China for treatment of ovary, breast non-small cell lung cancer. In present study we evaluated pharmacokinetic tissue distribution characteristics Sprague-Dawley rats Beagle dogs. A rapid simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed determination plasma tissues. The concentrations both dogs initially declined steeply, followed by slow elimination after...