A5100411493- Advanced Breast Cancer Therapies
- Cancer Mechanisms and Therapy
- Chronic Lymphocytic Leukemia Research
- Cancer Immunotherapy and Biomarkers
- RNA modifications and cancer
- RNA Research and Splicing
- Acute Myeloid Leukemia Research
- HER2/EGFR in Cancer Research
- 14-3-3 protein interactions
- Ubiquitin and proteasome pathways
- Cancer-related molecular mechanisms research
- Protein Tyrosine Phosphatases
- Cancer therapeutics and mechanisms
- CAR-T cell therapy research
- Multiple Myeloma Research and Treatments
- Liver physiology and pathology
- Biochemical and Molecular Research
- Hematopoietic Stem Cell Transplantation
- RNA regulation and disease
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Chronic Myeloid Leukemia Treatments
- Peptidase Inhibition and Analysis
- RNA and protein synthesis mechanisms
- Inflammasome and immune disorders
China Pharmaceutical University
2014-2025
State Key Laboratory of Natural Medicine
2020-2025
Shaanxi Provincial People's Hospital
2023
Shanxi Medical University
2023
Beijing Anzhen Hospital
2023
Zhejiang University of Technology
2023
Capital Medical University
2023
Longgang Central Hospital
2023
Binzhou University
2022
Binzhou Medical University
2022
VISTA (V-domain Ig suppressor of T cell activation) is a novel immune checkpoint protein and represents promising target for cancer immunotherapy. Here, we report the design, synthesis, evaluation series methoxy-pyrimidine-based small molecule inhibitors with potent antitumor activity. By employing molecular docking microscale thermophoresis (MST) assay, identified lead compound A1 that binds to high affinity optimized its structure. A4 was then obtained, which exhibited strongest binding...
The epidermal growth factor receptor (EGFR) tertiary C797S mutation is an important cause of resistance to Osimertinib, which seriously hinders the clinical application Osimertinib. Developing proteolysis-targeting chimeras (PROTACs) targeting EGFR mutants can offer a promising strategy overcome drug resistance. In this study, some novel PROTACs were designed and synthesized based on new inhibitor displayed potent degradation effect in H1975-TM cells harboring EGFRL858R/T790M/C797S....
Blocking the PD-1/PD-L1 interaction has become an important strategy for tumor therapy, which shown outstanding therapeutic effects in clinical settings. However, unsatisfactory response rates and immune-related adverse limit use of anti-PD1/PD-L1 antibodies. Here, we report discovery identification S4-1, innovative small-molecule inhibitor PD-L1. In vitro, S4-1 effectively altered PD-L1/PD-1 interaction, induced PD-L1 dimerization internalization, improved its localization to endoplasmic...
Programmed cell death 1(PD-1)/programmed ligand 1(PD-L1) have emerged as one of the most promising immune checkpoint targets for cancer immunotherapy. Despite inherent advantages small-molecule inhibitors over antibodies, discovery has fallen behind that antibody drugs. Based on docking studies between small molecule inhibitor and PD-L1 protein, changing chemical linker from a flexible chain to an aromatic ring may improve its binding capacity which was not reported before. A series novel...
Targeting c-Met is a clinical trend for the precise treatment of HCC, but potential issue acquired drug resistance cannot be ignored. Targeted protein degradation technology has demonstrated promising prospects in disease and overcoming due to its special mechanism action. In this study, we designed synthesized two series novel degraders conducted systematic biological evaluation optimal compound H11. H11 exhibited good activity anti-HCC activity. Importantly, also more potent inhibitory...
MTDH-SND1 protein-protein interaction (PPI) plays an important role in the initiation and development of tumors, it is a target for treatment breast cancer. In this study, we identified synthesized series novel small-molecule inhibitors PPI. The representative compound C19 showed potent activity against PPI with IC50 487 ± 99 nM tight binding to SND1-purified protein Kd value 279 17 nM. Compound significantly degraded SND1 downregulated downstream at level. Further biological evaluations...
Novel 2-arylmethoxy-4-(2,2′-dihalogen-substituted biphenyl-3-ylmethoxy) benzylamine derivatives were designed, synthesized, and evaluated in vitro vivo against cancers as PD-1/PD-L1 inhibitors. Through the computer-aided structural optimization homogeneous time-resolved fluorescence (HTRF) assay, compound A56 was found to most strongly block interaction with an IC50 value of 2.4 ± 0.8 nM showed potent activity. 1H NMR titration results indicated that can tightly bind PD-L1 protein KD < 1 μM....
Objective This study conducted a comprehensive analysis of the members PTPN family and emphasized key role PTPN2 as potential therapeutic target diagnostic biomarker in improving survival rate PAAD. Method Oncomine was used to analyze pan-cancer expression gene family. The Cancer Genome Atlas (TCGA) data well Genotype-Tissue Expression (GTEx) were downloaded prognosis PTPNs. diagnosis PTPNs evaluated by experimental ROC curve. protein-protein interaction (PPI) network constructed combining...
Prostate cancer (PCa) is a common male with high incidence and mortality, hormonal therapy as the major treatment for PCa patients troubled by inevitable resistance that makes us identify novel targets PCa. Dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) was found to be an effective target of PCa, but research on its inhibitors rather little. In this work, potent DYRK2 inhibitor 43 (IC50 = 0.6 nM) acquired through virtual screening structural optimization, which...
Bleeding events after an acute coronary syndrome have a negative impact on prognosis. Available risk scores are limited by suboptimal accuracy, prediction of only in-hospital and absence patients treated with new antiplatelet agents in the current era widespread use percutaneous intervention.The BleeMACS (Bleeding complications Multicenter registry discharged Acute Coronary Syndrome) project is multicenter investigator-initiated international retrospective that enrolled more than 15 000...
Abstract Background DNA methyltransferase 3A (DNMT3A) often mutate on arginine 882 (DNMT3A R882 ) in acute myeloid leukemia (AML). AML patients with DNMT3A mutation are usually resistant to daunorubicin treatment; however, the associated mechanism is still unclear. Therefore, it urgent investigate resistance mutant. Method cell lines DNMT3A-wild type (DNMT3A-WT), and DNMT3A-Arg882His (DNMT3A-R882H) were constructed role of R882H proliferation, apoptosis cells’ sensitivity Danunorubin....
Abstract Prostate cancer (PCa) is one of the most prevalent cancers in men worldwide, and hormonal therapy plays a key role treatment PCa. However, drug resistance makes it urgent necessary to identify novel targets for PCa treatment. Herein, dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) found confirmed be highly expressed tissues cells, knock-down DYRK2 remarkably reduces burden vitro vivo. On base acting as promising target, we further discover selective inhibitor...
Breast cancer is the most common tumor in women, and selective cyclin-dependent kinase (CDK) 4/6 inhibitors played an important role treatment of breast cancer. Therefore, discovering CDK4/6 with great safety potent efficacy beneficial for treatment. In our work, lead compound 8 was identified through virtual screening; then, systematic structural optimization conducted to afford 42, which exhibited strong inhibition on showed high selectivity among 205 kinases. 42 possessed excellent...
Myeloid neoplasms (MN) tend to relapse and deteriorate. Exploring the genomic mutation landscape of MN using next-generation sequencing (NGS) is a great measure clarify mechanism oncogenesis progression MN.This multicenter retrospective study investigated 303 patients with NGS from 2019 2021. The characteristics in subgroups clinical value gene variants were analyzed.At least one was detected 88.11% (267/303). TET2 most common cohort, followed by GATA2, ASXL1, FLT3, DNMT3A, TP53. Among...