A5022333888- Estrogen and related hormone effects
- Cytokine Signaling Pathways and Interactions
- HER2/EGFR in Cancer Research
- Antibiotic Resistance in Bacteria
- Advanced Breast Cancer Therapies
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Inflammatory mediators and NSAID effects
- Cancer Mechanisms and Therapy
- NF-κB Signaling Pathways
- Microtubule and mitosis dynamics
- Airway Management and Intubation Techniques
- Ubiquitin and proteasome pathways
- PI3K/AKT/mTOR signaling in cancer
- HIV/AIDS drug development and treatment
- Melanoma and MAPK Pathways
- Cancer-related Molecular Pathways
- Natural product bioactivities and synthesis
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Respiratory Support and Mechanisms
- Drug Transport and Resistance Mechanisms
- thermodynamics and calorimetric analyses
- FOXO transcription factor regulation
- Chemical Synthesis and Analysis
Liaocheng People's Hospital
2003-2024
China Institute of Veterinary Drug Control
2024
Huashan Hospital
2022-2023
Fudan University
2022-2023
Minda Hospital
2020
Sun Yat-sen University
2020
Fifth Affiliated Hospital of Sun Yat-sen University
2020
Peking University International Hospital
2018
Charles River Laboratories (United Kingdom)
2018
Qingdao University
2012-2018
Breast cancer remains a leading cause of death in women, representing significant unmet medical need. Here, we disclose our discovery efforts culminating clinical candidate, 35 (GDC-9545 or giredestrant). is an efficient and potent selective estrogen receptor degrader (SERD) full antagonist, which translates into better antiproliferation activity than known SERDs (1, 6, 7, 9) across multiple cell lines. Fine-tuning the physiochemical properties enabled once daily oral dosing preclinical...
Previous studies have reported that a few inflammatory cytokines associations with systemic lupus erythematosus (SLE)-for example, IL-6, IL-17, and macrophage protein (MIP). This Mendelian randomization was conducted to further assess the causal correlations between 41 SLE.The two-sample utilized genetic variances of SLE from large publicly available genome-wide association study (GWAS) (7,219 cases 15,991 controls European ancestry) GWAS summary containing 8,293 healthy participants....
The discovery and optimization of a series 6,7-dihydro-5H-cyclopenta[d]pyrimidine compounds that are ATP-competitive, selective inhibitors protein kinase B/Akt is reported. initial design was guided by the use X-ray structures in complex with Akt1 closely related A. resulting demonstrate potent inhibition all three Akt isoforms biochemical assays poor other members cAMP-dependent kinase/protein G/protein C extended family block phosphorylation multiple downstream targets human cancer cell...
TYK2 is a JAK family protein tyrosine kinase activated in response to multiple cytokines, including type I IFNs, IL-6, IL-10, IL-12, and IL-23. Extensive studies of mice that lack expression indicate the IFN-α, IL-23 pathways, but not IL-6 or IL-10 are compromised. In contrast, there have been few role primary human cells. A genetic mutation at tyk2 locus results single patient has linked defects suggesting broad for cytokine responses. this article, we used panel novel potent small-molecule...
Herein we report our lead optimization effort to identify potent, selective, and orally bioavailable TYK2 inhibitors, starting with molecule 3. We used structure-based design discover 2,6-dichloro-4-cyanophenyl (1R,2R)-2-fluorocyclopropylamide modifications, each of which exhibited improved potency JAK1 JAK2 selectivity relative Further eventually led compound 37 that showed good enzyme interleukin-12 (IL-12) cell potency, as well acceptable cellular excellent oral exposure in mice. When...
There is a critical need for new antibacterial strategies to counter the growing problem of antibiotic resistance. In Gram-negative bacteria, outer membrane (OM) provides protective barrier against antibiotics and other environmental insults. The leaflet primarily composed lipopolysaccharide (LPS). Outer biogenesis presents many potentially compelling drug targets as this pathway absent in higher eukaryotes. Most proteins involved LPS biosynthesis transport are essential; however, few...
The two major Aurora kinases carry out critical functions at distinct mitotic stages. Selective inhibitors of these kinases, as well pan-Aurora inhibitors, show antitumor efficacy and are now under clinical investigation. However, the ATP-binding sites A B virtually identical, structural basis for selective inhibition has therefore not been clear. We report here a class bisanilinopyrimidine with excellent selectivity over B, both in enzymatic assays cellular phenotypic assays. Crystal...
The dramatic increase in the prevalence of multi-drug resistant Gram-negative bacterial infections and simultaneous lack new classes antibiotics is projected to result approximately 10 million deaths per year by 2050. We report on efforts target ATP-binding cassette (ABC) transporter MsbA, an essential inner membrane protein that transports lipopolysaccharide from leaflet periplasmic face membrane. demonstrate improvement a high throughput screening hit into compounds with on-target single...
Aurora kinase inhibitors have attracted a great deal of interest as new class antimitotic agents. We report novel based on pentacyclic scaffold. A prototype inhibitor 32 (AKI-001) derived from two early lead structures improves upon the best properties each parent and compares favorably to previously reported inhibitor, 39 (VX-680). The exhibits low nanomolar potency against both B enzymes, excellent cellular (IC50 < 100 nM), good oral bioavailability. Phenotypic assays show that are...
This study was designed to describe the clinical features and management outcomes of severe hand, foot mouth disease (HFMD).Data on 147 HFMD patients during an outbreak in 2009 were analyzed.Most under 3 years age; 102 (69.4%) boys. All had skin rashes fever ≥38°C. (n = 147, 100%) showed signs central nervous system involvement, such as lethargy 124, 84.4%), myoclonic jerks 76, 51.7%), or drowsiness 34, 23.1%). Respiratory symptoms mainly tachypnea 112, 76.2%) bradypnea 21, 14.3%). Common...
Invasion, metastasis and resistance to conventional chemotherapeutic agents are obstacles successful treatment of pancreatic cancer, a better understanding the molecular basis this malignancy may lead improved therapeutics. In present study, we investigated whether AKT2 silencing sensitized cancer L3.6pl, BxPC-3, PANC-1 MIAPaCa-2 cells gemcitabine via regulating PUMA (p53-upregulated modulator apoptosis) nuclear factor (NF)-κB signaling pathway. MTT, TUNEL, EMSA NF-κB reporter assays were...
Drug resistance remains a major unresolved obstacle for gastric cancer (GC) treatment. Recently, increasing studies have showen that microRNAs (miRNAs) are involved in chemotherapeutic and can potentially be applied to reverse drug cancers. The relationship between miRNA-149 expression cisplatin (DDP) GC cells is still unknown. Here, we detected miR-149 by using RT-PCR found of was downregulated SGC7901/DDP compared with SGC7901cells, indicating role determining cisplatin-resistance cells....
Estrogen receptor alpha (ERα) is a well-validated drug target for ER-positive (ER+) breast cancer. Fulvestrant FDA-approved to treat ER+ cancer and works through two mechanisms—as full antagonist selective estrogen degrader (SERD)—but lacks oral bioavailability. Thus, we envisioned "best-in-class" molecule with the same dual mechanisms as fulvestrant, but significant exposure. Through lead optimization, discovered tool 12 (GNE-149) improved degradation antiproliferative activity in both MCF7...
This study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and molecular characteristics
Members of the JAK family protein kinases mediate signal transduction from cytokine receptors to transcription factor activation. Over-stimulation these pathways is causative in immune disorders like rheumatoid arthritis, psoriasis, lupus, and Crohn's disease. A search for selective inhibitors a kinase has led our characterization previously unknown conformation arising presentation Tyr962 TYK2 an inhibitory small molecule via H-bonding interaction. minority domains Tyrosine residue this...
HB presents with the highest frequency of CTNNB1 mutations, resulting in activation Wnt signaling pathway. A number studies have demonstrated mutation contributed to development HB. However, limited research explored function lncRNAs mutation.We screened lncRNA expression profiles CTNNB1-mutated samples and identified associated malignant phenotype The association between immune microenvironment was investigated. biological further using vitro experiments.TUG1 as onco-lncRNA TUG1 shown be...