A5088943148- Hormonal Regulation and Hypertension
- Natural product bioactivities and synthesis
- Phytochemistry and Biological Activities
- Cancer therapeutics and mechanisms
- HER2/EGFR in Cancer Research
- Chronic Lymphocytic Leukemia Research
- Pharmacological Effects of Natural Compounds
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Phosphodiesterase function and regulation
- Crystal structures of chemical compounds
- Renin-Angiotensin System Studies
- Advanced Breast Cancer Therapies
- Phytochemistry and Bioactive Compounds
- Quinazolinone synthesis and applications
- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
- Esophageal Cancer Research and Treatment
- Sexual function and dysfunction studies
- Protein Kinase Regulation and GTPase Signaling
- PI3K/AKT/mTOR signaling in cancer
- Chemical synthesis and alkaloids
- Eicosanoids and Hypertension Pharmacology
- Plant-based Medicinal Research
- Synthesis and biological activity
Shanghai Institute of Pharmaceutical Industry
2012-2024
Ibero American University
2021
Zhejiang University
2014
Chinese Academy of Sciences
2005-2013
Shanghai Institute of Materia Medica
2005-2013
People's Hospital of Yangzhong
2011-2012
Yangzhou University
2011-2012
Shanghai Institutes for Biological Sciences
2008-2010
Gatekeeper T790 M mutation in EGFR is the most prevalent factor underlying acquired resistance. Acrylamide-bearing quinazoline derivatives are powerful irreversible inhibitors for overcoming Nevertheless, concerns about risk of nonspecific covalent modification have motivated development novel cysteine-targeting inhibitors. In this paper, we demonstrate that fluoro-substituted olefins can be tuned to alter Michael addition reactivity. Incorporation these into templates produced potent with...
The signal transduction of acetylated histone can be processed through a recognition module, bromodomain. Several inhibitors targeting BRD4, one the bromodomain members, are in clinical trials as anticancer drugs. Hereby, we report our efforts on discovery and optimization new series 2-thiazolidinones BRD4 along previous study. In this work, guided by crystal structure analysis, reversed sulfonamide group identified binding mode. A structure–activity relationship study led to several potent...
This letter describes the construction of conformationally constrained quinazoline analogues. Structure-activity relationship studies led to identification lead compound 9n . Compound exhibits effective in vitro activity against A431(WT,overexpression) and H1975([L858R/T790M]) cancer cell lines but is significantly less EGFR negative (SW620, A549, K562). was also assessed for potency enzymatic assays vivo antitumor studies. The results indicated that a potent kinase inhibitor both wild-type...
The cyclin-dependent kinase (CDK)4/6-cyclin D1-Rb-p16/ink4a pathway is responsible for regulating cell progression past the G1 restriction point during cycle. development of a majority human tumors associated with dysregulation this pathway, resulting in increased cancer proliferation. Both CDK4 and CDK6, well-validated drug targets, function primarily as catalytic enzymes that mediate phosphorylation retinoblastoma protein (Rb). Here, we determined SPH3643 novel potent antiproliferative...
Abstract A new iridoid alkaloid containing a spirolactone unit, plumericidine ( 1 ), was isolated from the flowers of Plumeria rubra L. cv. Acutifolia. Its structure elucidated by spectroscopic evidence and confirmed X‐ray diffraction crystallography. anticancer antiviral activities were evaluated, but found to be insignificant.
A new ursane-type triterpenoid, 3β-hydroxy-urs-30-p-Z-hydroxycinnamoyloxy-12-en-28-oic-acid (1), together with three known triterpenoids, 3β-hydroxy-urs-30-p-E-hydroxycinnamoyloxy-12-en-28-oic-acid (2), 2α,3β,19α-trihydroxy-urs-12-en-28-oic-acid (3), and ursolic acid (4), four lignans, pinoresinol (5), 9α-hydroxypinoresinol (6), (+)-medioresinol (7), (+)-kobusin (8), two steroids, β-sitosterol (9), daucosterol (10), were isolated from the whole parts of Teucrium viscidum. Their structures...
Small-molecule irreversible tyrosine kinase inhibitors as high potent agents have led to improvements in disease-free and overall survival patients with HER2-amplified cancer. The approved HER2 inhibitors, neratinib pyrotinib, both lack selectivity, leading off-target adverse events patients. development of mutation during treatment also hampers the progress treatment. We used a molecular hybridization strategy for structural optimizations, conjunction vitro vivo drug-like property...
Abstract Two new iridoid diastereoisomers (1, 2), together with five known compounds, were isolated from the flowers of Plumerian rubra L. cv. acutifolia . Their structures elucidated by means in‐depth spectroscopic and mass‐spectrometric analyses, particularly 1D 2D NMR spectroscopy. Copyright © 2008 John Wiley & Sons, Ltd.
On the basis of scaffold hopping, a novel series 2-alkyl-1-arylsulfonylprolinamides was discovered as 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) inhibitors. A representative compound 4ek, obtained through SAR and structure optimization studies, demonstrates excellent in vitro potency against 11β-HSD-1 dose-dependent vivo inhibition prednisone/prednisolone transformation biomarker study mice.
Renin is the rate-limiting enzyme in renin-angiotensin-aldosterone system (RAAS) which regulates blood pressure and renal function hence an attractive target for treatment of hypertension cardiovascular/renal diseases. However, development direct renin inhibitors (DRIs) with favorable oral bioavailability has been a longstanding challenge many years. This problem was thought to be because most reported DRIs were peptide-like structures or nonpeptide-like molecular weight (MW) > 600....
Abstract To profile the anti‐Coxsackie virus B3 constituents of Radix Astragali, an HPLC‐DAD‐MS n analytical method, combined with in vivo test, has been developed to identify active part, which demonstrated have potency inhibit proliferation cardiac muscle, alleviate infraction heart and elevate survival rate animal. By comparing their retention time MS data those obtained from authentic compounds published data, a total 19 compounds, including 11 isoflavonoids eight saponins, were...
R adamantly beats S: 11β-HSD1 is a target for treating metabolic syndrome. The isomer 5 was selected as starting point optimization and SAR studies. Inhibitor 8 w emerged after several rounds of optimization, showing cross-species inhibition human mouse 11β-HSD1. It also displays good DMPK profile in vitro, advanced to PK/PD evaluations vivo. results confirmed its dose-dependent activity mice.
Abstract A simple and specific analytical method for the simultaneous determination of two metabolites calycosin‐7‐ O‐β ‐ d ‐glucopyranoside, ‐glucuronic acid methyl ester (M‐1) calycosin (M‐2), in rat urine was developed using high‐performance liquid chromatography. Quercetin employed as an internal standard. The correlation coefficients calibration curves were higher than 0.999; both intra‐ inter‐day precisions determined their RSD did not exceed 10%. accuracy linear range investigated...