A5101573534- Phosphodiesterase function and regulation
- Cholinesterase and Neurodegenerative Diseases
- Chemical synthesis and alkaloids
- Blood Pressure and Hypertension Studies
- Liver physiology and pathology
- Phenothiazines and Benzothiazines Synthesis and Activities
- Neurological Disorders and Treatments
- Mast cells and histamine
- Liver Disease and Transplantation
- Neurological Disease Mechanisms and Treatments
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Enzyme function and inhibition
- Pneumocystis jirovecii pneumonia detection and treatment
- Synthesis and Catalytic Reactions
- Meat and Animal Product Quality
- GABA and Rice Research
- Protein Hydrolysis and Bioactive Peptides
- Food composition and properties
- Rice Cultivation and Yield Improvement
- Drug-Induced Hepatotoxicity and Protection
- Biochemical effects in animals
Guangdong Ocean University
2025
Sun Yat-sen University
2020-2024
Yangzhou University
2018
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and devastating lung disease lacking effective therapy. To identify whether phosphodiesterase-1 (PDE1) inhibition could act as novel target for the treatment of IPF, hit-to-lead structural optimizations were performed on PDE9/PDE1 dual inhibitor (R)-C33, leading to compound 3m with an IC50 2.9 nM against PDE1C, excellent selectivity across PDE subfamilies, reasonable drug-like properties, remarkable pharmacodynamic effects...
Although soft rice, with low amylose content (AC), has high eating and cooking quality (ECQ), its appearance is poor due to the opaque endosperm. Here, a novel rice AC but transparent was generated by knocking-down expression of SSSII-2, gene encoding one isoform soluble starch synthase (SSS). The physicochemical properties SSSII-2 RNAi are quite different from control more like popular "Nanjing 46". taste value assay further demonstrated that ECQ as 46", only retained endosperm under...
Vascular dementia (VaD) is the second commonest type of which lacks efficient treatments currently. Neuroinflammation as a prominent pathological feature VaD, highly involved in development VaD. In order to verify therapeutic potential PDE1 inhibitors against anti-neuroinflammation, memory and cognitive improvement were evaluated vitro vivo by potent selective inhibitor 4a. Also, mechanism 4a ameliorating neuroinflammation VaD was systematically explored. Furthermore, optimize drug-like...
Liver fibrosis is a common pathological feature of most chronic liver diseases with no effective drugs available. Phosphodiesterase 1 (PDE1), subfamily the PDE super enzyme, might work as potent target for by regulating concentration cAMP and cGMP. However, there are few PDE1 selective inhibitors, none has been investigated treatment yet. Herein, compound AG-205/1186117 dihydropyrimidine scaffold was selected hit virtual screening. A hit-to-lead structural modification led to series...
Phosphodiesterase 1 (PDE1) is a subfamily of PDE super enzyme families that can hydrolyze cyclic adenosine monophosphate and guanosine simultaneously. Currently, the number PDE1 inhibitors relatively few, significantly limiting their application. Herein, novel series quinolin-2(1H)-ones were designed rationally, leading to compound 10c with an IC50 15 nM against PDE1C, high selectivity across other PDEs, remarkable safety properties. Furthermore, we used lead as chemical tool explore whether...
Hepatic fibrosis commonly exists in chronic liver disease and would eventually develop to cirrhosis cancer with high fatality. Phosphodiesterase-9 (PDE9) has attracted profound attention as a drug target because of its highest binding affinity among phosphodiesterases (PDEs) cyclic guanosine monophosphate. However, no published study reported PDE9 inhibitors potential agents against hepatic yet. Herein, structural modification from starting hit LL01 led lead 4a, which exhibited an IC50 value...
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with no ideal drugs. Our previous research demonstrated that phosphodiesterase 1 (PDE1) could be promising target for the treatment of IPF. However, only few selective PDE1 inhibitors are available, and mechanism recognition between protein not fully understood. This study carried out step-by-step optimization dihydropyrimidine hit Z94555858. By targeting metal pocket PDE1, lead compound 3f was obtained, exhibiting an IC50 value 11...