A5100721183- Cancer-related Molecular Pathways
- RNA Interference and Gene Delivery
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Advanced Drug Delivery Systems
- Gout, Hyperuricemia, Uric Acid
- Advancements in Transdermal Drug Delivery
- DNA Repair Mechanisms
- Plant Molecular Biology Research
- Lymphoma Diagnosis and Treatment
- Ocular Surface and Contact Lens
- Monoclonal and Polyclonal Antibodies Research
- Chronic Lymphocytic Leukemia Research
- HER2/EGFR in Cancer Research
- Pharmacological Effects of Natural Compounds
- Microtubule and mitosis dynamics
- Dermatology and Skin Diseases
- Cancer, Hypoxia, and Metabolism
- Alcohol Consumption and Health Effects
- HIV/AIDS drug development and treatment
- Asthma and respiratory diseases
- Bacteriophages and microbial interactions
- Ubiquitin and proteasome pathways
Beijing Shijitan Hospital
2025
Capital Medical University
2022-2025
Sichuan University
2021-2024
First Affiliated Hospital of Soochow University
2015-2023
Institute of Microbiology
2021-2023
Chinese Academy of Sciences
2011-2023
Suzhou Institute of Nano-tech and Nano-bionics
2023
Soochow University
2015-2023
University of Chinese Academy of Sciences
2021-2022
Capital University
2022
We recently reported the discovery of AM-8553 (1), a potent and selective piperidinone inhibitor MDM2-p53 interaction. Continued research investigation N-alkyl substituent this series, focused in particular on previously underutilized interaction shallow cleft MDM2 surface, led to one-carbon tethered sulfone which gave rise substantial improvements biochemical cellular potency. Further produced AMG 232 (2), is currently being evaluated human clinical trials for treatment cancer. Compound 2...
A microdose study of metformin was conducted to investigate the predictability drug–drug interactions at therapeutic dose (ThD). Healthy subjects received a (100 µg) or ThD (250 mg) orally, with without potent and competitive multidrug toxin extrusion (MATE) inhibitor, pyrimethamine (50 mg, p.o.), in crossover fashion. Pyrimethamine significantly reduced renal clearance by 23 35% ThD, respectively. At but not microdose, it caused significant increases maximum concentration (Cmax) area under...
Structure-based rational design led to the discovery of novel inhibitors MDM2–p53 protein–protein interaction. The affinity these compounds for MDM2 was improved through conformational control both piperidinone ring and appended N-alkyl substituent. Optimization afforded 29 (AM-8553), a potent selective inhibitor with excellent pharmacokinetic properties in vivo efficacy.
KRAS mutations are broadly recognized as promising targets for tumor therapy. T cell receptors (TCRs) can specifically recognize mutant neoantigens presented by human lymphocyte antigen (HLA) and mediate responses to eliminate cells. In the present study, we identify two TCRs specific 9-mer KRAS-G12V neoantigen in context of HLA-A*11:01. The TCR-T cells constructed display cytokine secretion cytotoxicity upon co-culturing with varied expressing mutation. Moreover, 1-2C show anti-tumor...
Immune checkpoint therapy (ICT) with a monoclonal antibody (MAb) against programmed cell death protein 1 (PD-1) is powerful clinical treatment for tumors. Cemiplimab human IgG4 approved in 2018 and the first MAb proven to be effective locally advanced basal carcinoma. Here, we report crystal structure of cemiplimab bound PD-1 effects N-glycosylation on interactions cemiplimab. The cemiplimab/PD-1 complex shows that mainly binds its heavy chain, whereas light chain serves as predominant...
Structure-based rational design and extensive structure-activity relationship studies led to the discovery of AMG 232 (1), a potent piperidinone inhibitor MDM2-p53 association, which is currently being evaluated in human clinical trials for treatment cancer. Further modifications 1, including replacing carboxylic acid with 4-amidobenzoic acid, afforded AM-7209 (25), featuring improved potency (KD from ITC competition was 38 pM, SJSA-1 EdU IC50 = 1.6 nM), remarkable pharmacokinetic...
Summary Although chimeric antigen receptor T cells (CAR‐T) targeted at CD19 or CD22 have achieved high complete remission (CR) in refractory/relapsed B‐cell acute lymphoblastic leukaemia (B‐ALL), it is uncertain if allogeneic haematopoietic stem cell transplantation (allo‐HSCT) should be performed after CAR‐T therapy to accomplish a sustainable remission. Fifty‐two cases with relapsed/refractory B‐ALL who underwent allo‐HSCT CR by were enrolled. The median time from infusion was 50 (34–98)...
Osteoarthritis (OA) significantly impacts the elderly, leading to disability and decreased quality of life. While hyaluronic acid (HA) chondroitin sulfate (CS) are recognized for their therapeutic potential in OA, effects on extracellular matrix (ECM) degradation not well understood. This study investigates impact HA CS, individually combined, ECM OA underlying mechanisms.
Qijiafuzheng formula (QJFZF), a Traditional Chinese Medicine used to treat lung cancer and mitigate chemotherapy side effects, was studied clarify its impact on the tumor immune microenvironment (TIME). Using network pharmacology experimental validation, 39 overlapping targets were identified from 579 QJFZF-related 752 adenocarcinoma (LUAD)-TIME targets. Key genes (CCL3, IL10, CXCL10, FOXP3, CD86) correlated negatively with purity positively CD8+ T-cell infiltration. CXCL10 emerged as core...
Abstract Whole‐cell vaccines that provide broad‐spectrum antigens have been explored for recent decades. But so far, they revealed limited success in clinical trials, possibly owing to their inefficiency targeting immune organs and antigen‐presenting cells (APCs). Herein, a facile strategy is developed convert the whole‐cell into nanoscale size promote lymphatic migration subsequent intracellular antigen presentation maximize responses. Briefly, study designs multiple delivery platform based...
ABSTRACT Telaprevir is a linear, peptidomimetic small molecule that inhibits hepatitis C virus (HCV) replication by specifically inhibiting the NS3·4A protease. In phase 3 clinical studies, telaprevir in combination with peginterferon and ribavirin (PR) significantly improved sustained virologic response (SVR) rates genotype 1 chronic HCV-infected patients compared PR alone. who do not achieve SVR after treatment telaprevir-based regimens, variants mutations protease region have been...
In rice, and other major cereal grass crops, stomata are arranged in linear files parallel to the long growth axis of leaves. Each stomatal unit comprises two dumbbell-shaped guard cells flanked by subsidiary cells. These morphological developmental characteristics enable respond environmental changes more efficiently. Cyclin-dependent kinases (CDKs) their cyclin partners co-ordinate cell proliferation differentiation during development multicellular organisms. contrast animals, plants have...
Human trophoblast cell surface antigen 2 (TROP-2) is an important target of tumor therapy, and antibody-drug conjugates with sacituzumab targeting TROP-2 have been approved for the treatment triple-negative breast cancer. Here, we report crystal structures TROP-2-ECD, which can be either cis- or trans-dimers depending on distinct but overlapping interfaces used to engage monomers. The trans-tetrameric forms also assembled a non-overlapping interface trans-dimerization, suggesting that...
Asthma is a chronic lung inflammation which affects many people. As current therapies for asthma mainly rely on administration of glucocorticoids and have side effects, new therapy needed. In this study, we investigated Nepeta bracteata Benth., traditional Uygur Herb, its therapeutics effect in OVA induced asthmatic mice model. Treatment sensitized with extract from Benth. demonstrated improved pathology, as well reduced infiltration eosinophil neutrophil. also contributed to the rebalance...