A5002576867- Chronic Myeloid Leukemia Treatments
- Peptidase Inhibition and Analysis
- Neuropeptides and Animal Physiology
- Diabetes Treatment and Management
- Chronic Lymphocytic Leukemia Research
- Radical Photochemical Reactions
- Click Chemistry and Applications
- Sulfur-Based Synthesis Techniques
- Quinazolinone synthesis and applications
- Catalytic C–H Functionalization Methods
- Acute Myeloid Leukemia Research
- Gastrointestinal Tumor Research and Treatment
- Chemical Synthesis and Analysis
- Synthesis and biological activity
- Colorectal Cancer Treatments and Studies
- Protease and Inhibitor Mechanisms
- Protein Degradation and Inhibitors
- Oxidative Organic Chemistry Reactions
- Cancer Research and Treatments
- Hepatitis C virus research
- Gastric Cancer Management and Outcomes
- Protein Tyrosine Phosphatases
- Cancer Genomics and Diagnostics
- Neurobiology and Insect Physiology Research
- Biochemical and Molecular Research
National Health Research Institutes
2011-2024
National Defense Medical Center
2005
Institute of Biological Chemistry, Academia Sinica
1999-2001
ITRI International
2001
National Taiwan University
1993-1999
GTx (United States)
1999
University of Pittsburgh
1993-1994
Dengue virus (DENV) causes disease globally, resulting in an estimated 25 to 100 million new infections per year. No effective DENV vaccine is available, and the current treatment only supportive. Thus, there urgent need develop therapeutic agents cure this epidemic disease. In present study, we identified a potential small-molecule inhibitor, BP13944, via high-throughput screening (HTS) of 60,000 compounds using stable cell line harboring efficient luciferase replicon serotype 2 (DENV-2)....
Fibroblast activation protein (FAP) belongs to the prolyl peptidase family. FAP inhibition is expected become a new antitumor target. Most known inhibitors often resemble dipeptide cleavage products, with boroproline at P1 site; however, these also inhibit DPP-IV, DPP-II, DPP8, and DPP9. Potent selective inhibitor needed in evaluating that as therapeutic Therefore, it important develop for use of target validation. To achieve this, optimization nonselective DPP-IV 8 led discovery class...
Ligand efficiency (LE) and lipophilic (LipE) are two important indicators of "drug-likeness", which dependent on the molecule's activity physicochemical properties. We recently reported a furano-pyrimidine Aurora kinase inhibitor 4 (LE = 0.25; LipE 1.75), with potent in vitro; however, was inactive vivo. On basis insights obtained from X-ray co-crystal structure lead 4, various solubilizing functional groups were introduced to optimize both Emphasis placed identifying potential leads...
A series of acyl silanes including aliphatic-, aromatic-, and bis-acyl silanes, as well the bearing other substituents such a bromine atom alkenyl, succinimide, carbonyl groups, were prepared, their reactions with samarium diiodide or tributylstannane studied. The occurred in various manners reductions, reductive alkylations, intramolecular radical cyclizations, pinacol couplings, aldol reactions, Tishchenko depending on nature substrates reaction conditions. Acyl generally reduced to give...
Most anaplastic lymphoma kinase (ALK) inhibitors adopt a type I binding mode, but only limited II ALK structural studies are available. Herein, we present the structure of in complex with N1-(3-4-[([5-(tert-butyl)-3-isoxazolyl]aminocarbonyl)amino]-3-methylphenyl-1H-5-pyrazolyl)-4-[(4-methylpiperazino)methyl]benzamide (5a), novel inhibitor adopting mode. It revealed 5a resulted conformational change and reposition activation loop, αC-helix, juxtamembrane domain, which all important domains...
Dipeptidyl peptidase IV (DPP-IV) is a drug target in the treatment of human type II diabetes. It membrane protein with single transmembrane domain (TMD) anchoring extracellular catalytic to membrane. DPP-IV active as dimer, two dimer interacting surfaces located extracellularly. In this study, we demonstrate that TM promotes dimerization and rescues monomeric mutants into partial dimers, which specific irreplaceable by TMs other proteins. By bioluminescence resonance energy transfer (BRET)...
Overexpression or/and activating mutation of FLT3 kinase play a major driving role in the pathogenesis acute myeloid leukemia (AML). Hence, pharmacologic inhibitors are therapeutic potential for AML treatment. In this study, BPR1J-340 was identified as novel potent inhibitor by biochemical activity (IC50 approximately 25 nM) and cellular proliferation (GC50 5 assays. inhibited phosphorylation STAT5 triggered apoptosis FLT3-ITD+ cells. The pharmacokinetic parameters rats were determined. also...
5-Exo cyclizations of primary and secondary radicals with acylsilanes successfully give cyclopentyl silyl ethers. The corresponding 6-exo are sensitive to changes the size groups. Secondary undergo more slowly. Reaction aryl radical acylsilane proceeds well for 5-exo cyclization but not cyclization. Vinyl best results in low yields (∼30%) cyclizations. Intramolecular vinyl enol ethers regiospecifically.
Treatment of ω-bromo acylsilanes under standard radical allylation (or addition) conditions provides 1-alkyl- 1-alkyl) cycloalkanols by a sequence cyclization, Brook rearrangement, addition, and fragmentation reduction).
Dipeptidyl peptidase IV (DPP-IV) inhibitors are expected to become a new type of antidiabetic drugs. Most known DPP-IV often resemble the dipeptide cleavage products, with proline mimic at P1 site. As off-target inhibitions DPP8 and/or DPP9 have shown profound toxicities in vivo studies, it is important develop selective for clinical usage. To achieve this, class 2-[3-[[2-[(2S)-2-cyano-1-pyrrolidinyl]-2-oxoethyl]amino]-1-oxopropyl]-based was synthesized. SAR studies resulted number...
Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) plays an important role in one-carbon metabolism. The MTHFD2 gene is upregulated various cancers but very low or undetectable normal proliferating cells, and therefore a potential target for cancer treatment. In this study, we present the structure of complex with xanthine derivative 15, which allosterically binds to coexists substrate analogue. A kinetic study demonstrated uncompetitive inhibition by 15. Allosteric inhibitors often provide...
Drug resistance due to acquired mutations that constitutively activate c-KIT is a significant challenge in the treatment of patients with gastrointestinal stromal tumors (GISTs). Herein, we identified 1-(5-ethyl-isoxazol-3-yl)-3-(4-{2-[6-(4-ethylpiperazin-1-yl)pyrimidin-4-ylamino]-thiazol-5-yl}phenyl)urea (10a) as potent inhibitor against unactivated and activated c-KIT. The binding 10a induced rearrangements DFG motif, αC-helix, juxtamembrane domain, activation loop switch back its...
The kinetics of the radical cyclizations acylsilanes is probed by construction an intramolecular competition system. In this system, known rate constants olefin are used as internal clock. At benzene reflux temperature (80 °C), cyclization for 5-exo with primary radicals on order 106 s-1. corresponding secondary and 6-exo lie 105 slower fall in range 104 Substituents silicon affect rates cyclization. Large silyl groups reduce rate, more serious type cyclizations. Electron-withdrawing increase