A5010843465- Diabetes Treatment and Management
- Neuropeptides and Animal Physiology
- Peptidase Inhibition and Analysis
- Lipid metabolism and biosynthesis
- Receptor Mechanisms and Signaling
- HIV/AIDS drug development and treatment
- Chemical Synthesis and Analysis
- Pancreatic function and diabetes
- Synthesis and Biological Evaluation
- Endoplasmic Reticulum Stress and Disease
- HIV Research and Treatment
- Logic, Reasoning, and Knowledge
- Fluorine in Organic Chemistry
- Mass Spectrometry Techniques and Applications
- Genetic Mapping and Diversity in Plants and Animals
- Ion channel regulation and function
- Urinary Bladder and Prostate Research
- Neuroscience and Neuropharmacology Research
- Bayesian Modeling and Causal Inference
- Vehicle Noise and Vibration Control
- Protein Structure and Dynamics
- Click Chemistry and Applications
- Formal Methods in Verification
- Monoclonal and Polyclonal Antibodies Research
- Electrical Fault Detection and Protection
Shanghai Electric (China)
2021-2024
University of Southern California
2022-2024
Shanghai University of Engineering Science
2023
Jilin University
2022
Merck & Co., Inc., Rahway, NJ, USA (United States)
2009-2019
Weatherford College
2011
Nonpeptide agonists of each the five somatostatin receptors were identified in combinatorial libraries constructed on basis molecular modeling known peptide agonists. In vitro experiments using these selective compounds demonstrated role subtype-2 receptor inhibition glucagon release from mouse pancreatic alpha cells and subtype-5 as a mediator insulin secretion beta cells. Both regulated growth hormone rat anterior pituitary gland. The availability high-affinity, subtype-selective for...
The discovery of vibegron, a potent and selective human β3-AR agonist for the treatment overactive bladder (OAB), is described. An early-generation clinical MK-0634 (3) exhibited efficacy in humans OAB, but development was discontinued due to unacceptable structure-based toxicity preclinical species. Optimization series second-generation pyrrolidine-derived agonists included reducing risk phospholipidosis, formation disproportionate metabolites, high levels circulating metabolites These...
Miniaturization and parallel processing play an important role in the evolution of many technologies. We demonstrate application miniaturized high-throughput experimentation methods to resolve synthetic chemistry challenges on frontlines a lead optimization effort develop diacylglycerol acyltransferase (DGAT1) inhibitors. Reactions were performed ∼1 mg scale using glass microvials providing capability that was used study challenging SNAr reaction. The availability robust conditions...
A mild, chemoselective, and generally high-yielding method for the reductive scission of heterocyclic thioethers is described. Suitable heterocycles have a thioether substituent at 2-position relative to ring heteroatom. The convenient straightforward demonstrated with reactants which are not compatible standard Raney nickel conditions such as sulfides, sulfones, thiophenes. In addition, benzyl esters, amides, carbamates tolerated by reaction conditions.
[reaction: see text] Condensation of aromatic or aliphatic esters with resin-supported acetyl carboxylic acids 2, followed by cyclization hydrazines hydroxylamine, activation the linker, and cleavage using amines provides highly substituted, isomeric pyrazoles isoxazoles 5. This general method gives products in excellent yields purities which ratio two isomers can be easily controlled. A variation this scheme generates 1,4,5- 1,3, 4-trisubstituted related isoxazoles. Post-cleavage reduction...
To address the issues of low automation, reliance on manual screening by professionals, and long detection cycles in current urban drainage pipeline defect detection, this study proposes an improved object algorithm called EFE-SSD (enhanced feature extraction SSD), based SSD (Single Shot MultiBox Detector) network. Firstly, RFB_s module is added to backbone network enhance its capabilities. Additionally, multiple scale features are fused improve performance small target defects some extent....
DGAT2 plays a critical role in hepatic triglyceride production, and data suggests that inhibition of could prove to be beneficial treating number disease states. This article documents the discovery optimization selective small molecule inhibitor as well pharmacological proof biology mouse model production.
We report the discovery of a novel series DGAT1 inhibitors in benzimidazole class with piperdinyl-oxy-cyclohexanecarboxylic acid moiety. This possesses significantly improved selectivity against A2A receptor, no ACAT1 off-target activity at 10 μM, and higher aqueous solubility free fraction plasma as compared to previously reported pyridyl-oxy-cyclohexanecarboxylic series. In particular, 5B was shown possess an excellent profile by screening it panel more than 100 biological targets....
A series of conformationally restricted acetanilides were synthesized and evaluated as β3-adrenergic receptor agonists (β3-AR) for the treatment overactive bladder (OAB). Optimization studies identified a five-membered ring preferred conformational lock acetanilide. Further optimization both aromatic thiazole regions led to compounds such 19 29, which have good balance potency selectivity. These significantly reduced intrinsic clearance compared our initial pyridylethanolamine β3-AR thus...
High-conductance calcium-activated potassium (Maxi-K) channels are present in smooth muscle where they regulate tone. Activation of Maxi-K causes hyperpolarization and shortening action-potential duration, which would limit calcium entry through voltage-dependent leading to relaxation. Although appear indirectly mediate the relaxant effects a number agents, activators that bind directly channel with appropriate potency pharmacological properties useful for proof-of-concept studies not...
Prolylcarboxypeptidase (PRCP) is a serine protease that catalyzes the cleavage of C-terminal amino acids linked to proline in peptides. It ubiquitously expressed and involved regulating blood pressure, proliferation, inflammation, angiogenesis, weight maintenance. To identify candidate proximal target engagement markers for PRCP inhibition central nervous system, we profiled peptidome human cerebrospinal fluid look substrates using MS-based vitro substrate profiling assay. These experiments...
Methodology was developed to afford rapid characterization of multicomponent mixtures small organic molecules prepared by split-and-mix combinatorial synthesis. This methodology involved the use liquid chromatography mass spectrometry (LC/MS) combined with correlation analysis measured versus predicted electrospray ionization spectra. Low-resolution spectra complex revealed predictable patterns that confirm library products, assisted in identifying chemical synthesis errors, and assessed...
We report the design and synthesis of a series novel DGAT1 inhibitors in benzimidazole class with pyridyl-oxy-cyclohexanecarboxylic acid moiety. In particular, compound 11A is potent inhibitor excellent selectivity against ACAT1. Compound significantly reduces triglyceride excursion lipid tolerance tests (LTT) both mice dogs at low plasma exposure. An vivo study des-fluoro analogue 10A indicates that this compounds appears to distribute intestine preferentially over plasma. The propensity...
The mechanism of ginsenoside Rh3 activity against cancer remains unclear. This study aimed to investigate the underlying mechanism. effects on cell proliferation, migration and invasion, cycle apoptosis were analyzed using CCK-8 assay, transwell assay flow cytometry, respectively. RNA transcriptome was sequenced data by R software. Protein expression protein-protein interactions determined Western blotting co-immunoprecipitation, results showed inhibited HCT116 migration, arrested cells at...