• Biomolecules & Therapeutics
• /
• v.26 no.2
• /
• pp.201-209
• /
• 2018

G protein-coupled receptor 119 (GPR119) is expressed in the pancreas and gastrointestinal tract, and its activation promotes insulin secretion in the beta cells of the pancreatic islets as well as the secretion of glucagon-like peptide-1 (GLP-1) in intestinal L cells, consequently improving glucose-stimulated insulin secretion. Due to this dual mechanism of action, the development of small-molecule GPR119 agonists has received significant interest for the treatment of type 2 diabetes. We newly synthesized 1,2,4-triazolone derivatives of GPR119 agonists, which demonstrated excellent outcomes in a cyclic adenosine monophosphate (cAMP) assay. Among the synthesized derivatives, YH18968 showed cAMP=2.8 nM; in GLUTag cell, GLP-1secretion=2.3 fold; in the HIT-T15 cell, and insulin secretion=1.9 fold. Single oral administration of YH18968 improved glucose tolerance and combined treatment with a dipeptidyl peptidase 4 (DPP-4) inhibitor augmented the glucose lowering effect as well as the plasma level of active GLP-1 in normal mice. Single oral administration of YH18968 improved glucose tolerance in a diet induced obese mice model. This effect was maintained after repeated dosing for 4 weeks. The results indicate that YH18968 combined with a DPP-4 inhibitor may be an effective therapeutic candidate for the treatment of type 2 diabetes.

• Korean Journal of Materials Research
• /
• v.16 no.4
• /
• pp.253-256
• /
• 2006

The blue emitting OLEDs using GDI host-dopant phosphors have been fabricated and characterized. In the device fabrication, 2-TNATA [4,4',4'-tris(2-naphthylphenyl-phenylamino)- triphenylamine] as a hole injection material and NPB [N,N'-bis(1-naphthyl)-N,N'-diphenyl-1,1'-biphenyl-4,4'-diamine] as a hole transport material were deposited on the ITO(indium thin oxide)/glass substrate by vacuum evaporation. And then, blue color emission layer was deposited using GDI602 as a host material and GDI691 as a dopant. Finally, small molecule OLEDs with structure of ITO/2-TNATA/NPB/GDI602:GDI691/Alq3/LiF/Al were obtained by in-situ deposition of Alq3, LiF and Al as the electron transport material, electron injection material and cathode, respectively. Blue OLEDs fabricated in our experiments showed the color coordinate of CIE(0.14, 0.16) and the maximum power efficiency of 1.1 lm/W at 11 V with the peak emission wavelength of 464 nm.

• Journal of the Korean Society for Aeronautical & Space Sciences
• /
• v.33 no.1
• /
• pp.78-84
• /
• 2005

In the chemical laser system with a radial expansion nozzle array, the laser beam generation is achieved by mixing F atom from supersonic nozzle and $D_{2}$ molecule from holes of round-bended supply line. Based on that the fuel injection angle with main stream has a great influence of performance on supersonic combustor, the effects of $D_{2}$ injection angles with the main F flow on mixing enhancement are numerically investigated. The results are discussed by comparison with three cases of $D_{2}$ injection angles; $10^{o}$, $20^{o}$ and $40^{o}$ with the main flow direction. Major results reveal that as the $D_{2}$ injection angle increases, the maximum small signal gains and the static pressure in the laser cavity become higher. Consequently, the $D_{2}$ injection angle between $20^{o}$ and $40^{o}$ is recommended as an optimized geometric parameter in consideration of both of high gains and low cavity pressure.

• Journal of the Semiconductor & Display Technology
• /
• v.6 no.2 s.19
• /
• pp.19-23
• /
• 2007

The blue emitting OLEDs using TMP-BiP[(4'-Benzoylferphenyl-4-yl)phenyl-methanone-Diethyl(biphenyl-4-ymethyl) phosphonate] host and DJNBD-1 dopant have been fabricated and characterized. In the device fabrication, 2-TNATA [4,4',4"-tris(2-naphthylphenyl-phenylamino)-triphenylamine] as a hole injection material and NPB [N,N'-bis(1-naphthyl)N,N'-diphenyl-1,1'-biphenyl-4,4'-diamine] as a hole transport material were deposited on the ITO(indium tin oxide)/glass substrate by vacuum thermal evaporation method. Followed by the deposition, blue color emission layer was deposited using TMP-BiP as a host material and DJNBD-1 as a dopant. Finally, small molecule OLEDs with structure of $ITO/2-TNATA/NPB/TMP-BiP:DJNBD-l/Alq_3/LiF/Al$ were obtained by in-situ deposition of $Alq_3$, LiF and Al as the electron transport material, electron injection material and cathode, respectively. The effect of dopant into host material of the blue OLEDs was studied. The blue OLEDs with DJNBD-1 dopant showed that the maximum current and luminance were found to be about 34 mA and $8110\;cd/m^2$ at 11 V, respectively. In addition, the color coordinate was x=0.17, y=0.17 in CIE color chart, and the peak emission wavelength was 440 nm. The maximum current efficiency of 2.15 cd/A at 7 V was obtained in this experiment.

• The Korean Journal of Physiology
• /
• v.17 no.1
• /
• pp.1-11
• /
• 1983

1) The two microelectrode method was used to voltage clamp small preparations of rabbit sinoatrial node. The kinetics of hyperpolarization activated inward current, $i_f$ were analysed. 2) The hrperpolarization pulses activated $i_f$ current in the presence of $10^{-7}g/ml$ TTX and 2 mM $Mn^{2+}$. The activation range was in between -45 mV to -75 mV. The current magnitude was increased and time course was faster by strong hyperpolarization pulses. 3) Standard envelope tests indicated that this current is exponentially controlled by single gate. 4) Semilogarithmic plot of $i_f$ activation versus time was found to be linear in the activation range. The decrease in current magnitude and the shifts in activation curve and rate constants curve to the hyperpolarizing direction were obtained with $Ba^{2+}$, indicating that $Ba^{2+}$ shifts the voltage dependence of the gating kinetics, were partially reversed by 24 mM $K^+$.

• Journal of Microbiology and Biotechnology
• /
• v.18 no.11
• /
• pp.1862-1867
• /
• 2008

Streptochlorin is a small molecule isolated from marine Streptomyces sp. that is known to have antiangiogenic and anticancer properties. In this study, we examined the effects of this compound on reactive oxygen species (ROS) production and the association of these effects with apoptotic tumor cell death, using a human hepatocarcinoma Hep3B cell line. The results of this study demonstrated that streptochlorin mediates ROS production, and that this mediation is followed by a decrease in the mitochondrial membrane potential (MMP, ${\Delta}{\Psi}_m$), activation of caspase-3, and downregulation of antiapoptotic Bcl-2 protein. The quenching of ROS generation by N-acetyl-L-cysteine administration, a scavenger of ROS, reversed the streptochlorin-induced apoptosis effects via inhibition of ROS production, MMP collapse, and the subsequent activation of caspase-3. These observations clearly indicate that ROS are involved in the early molecular events in the streptochlorin-induced apoptotic pathway. Taken together, our data imply that streptochlorin-induced ROS is a key mediator of MMP collapse, which leads to the caspase-3 activation, culminating in apoptosis.

• Journal of Microbiology and Biotechnology
• /
• v.28 no.8
• /
• pp.1401-1411
• /
• 2018

The serine-threonine kinase AKT plays a pivotal role in tumor progression and is frequently overactivated in cancer cells; this protein is therefore a critical therapeutic target for cancer intervention. We aimed to identify small molecule inhibitors of the pleckstrin homology (PH) domain of AKT to disrupt binding of phosphatidylinositol-3,4,5-trisphosphate (PIP3), thereby downregulating AKT activity. Liposome pulldown assays coupled with fluorescence spectrometry were used to screen flavonoids for inhibition of the AKT PH-PIP3 interaction. Western blotting was used to determine the effects of the inhibitors on AKT activation in cancer cells, and in silico docking was used for structural analysis and optimization of inhibitor structure. Several flavonoids showing up to 50% inhibition of the AKT PH-PIP3 interaction decreased the level of AKT activation at the cellular level. In addition, the modified flavonoid showed increased inhibitory effects and the approach would be applied to develop anticancer drug candidates. In this study, we provide a rationale for targeting the lipid-binding domain of AKT, rather than the catalytic kinase domain, in anticancer drug development.

• Korean Journal of Food Science and Technology
• /
• v.33 no.1
• /
• pp.7-11
• /
• 2001

The influence of temperature and calcium concentration on the gelation kinetics of purified Aigeok system has been investigated by small deformation oscillatory measurement. DE(degree of esterification) of the present sample was indicated of low methoxyl Aigeok polysaccharide by FT-IR. The calcium induced gelation of Aigeok has been studied. Both moduli reached the saturation value during the period of experiments. Rate constant increased with increasing calcium concentration, however above 4.08 mM calcium chloride caused a sudden drop in gel strength. The experimental result that the decrease in gel strength at high calcium concentration was seems to be phase separation or competitive inhibition between calcium ions. The storage and loss shear moduli decreased with increasing temperature. The rate constant of Aigeok system remarkably dropped above $35^{\circ}C$. Thus hydrogen bonding is prior to hydrophobic interaction for Aigeok molecule.

• Journal of Integrative Natural Science
• /
• v.5 no.2
• /
• pp.107-119
• /
• 2012

Polymerization of monomeric amyloid-${\beta}$ peptides ($A{\beta}$) into soluble oligomers and insoluble fibrils is one of the major pathways triggering the pathogenesis of Alzheimer's disease (AD). Using small molecules to prevent the polymerization of $A{\beta}$ peptides can, therefore, be an effective therapeutic strategy for AD. In this study, we investigated the effects of mono- and bi-flavonoids on $A{\beta}42$ toxicity and fibrillogenesis and found that the bi-flavonoid, taiwaniaflavone (TF) effectively and specifically inhibits $A{\beta}$ toxicity and fibrillogenesis. Compared to TF, the mono-flavonoid apigenin (AP) is less effective and less specific. Our data showed that differential effects of the mono- and bi-flavonoids on $A{\beta}$ fibrillogenesis correlate with their varying cytoprotective efficacies. We also found that other bi-flavonoids, namely 2',8"-biapigenin, amentoflavone, and sumaflavone, can also effectively inhibit $A{\beta}$ toxicity and fibrillogenesis, implying that the participation of two mono-flavonoids in a single bi-flavonoid molecule enhanced their activity. Bi-flavonoids, while strongly inhibited $A{\beta}$ fibrillogenesis, accumulated nontoxic $A{\beta}$ oligomeric structures, suggesting that these are off-pathway-oligomers. Moreover, TF abrogated the toxicity of preformed $A{\beta}$ oligomers and fibrils, indicating that TF and other bi-flavonoids may also reduce the toxicity of toxic $A{\beta}$ species. Altogether, our data clearly show that bi-flavonoids, possibly due to the possession of two $A{\beta}$ binders separated by an appropriate size linker, are likely to be promising therapeutics to suppress $A{\beta}$ toxicity.

• Journal of the Korean Institute of Electrical and Electronic Material Engineers
• /
• v.11 no.8
• /
• pp.581-586
• /
• 1998

This paper describes athermally stimulated displacement current (TSDC) of arachidic acid(AA) and polyamic acid alkylamine salts(PAAS) Langmuir-Blodgett(LB) films, which is a precursor of polyimide(PI). The TSDC measurements of AA LB film were performed from temperature to about 11$0^{\circ}C$ at a rate of 0.2$^{\circ}C$/ｓ inside a vacuum chamber for a reference. And the TSDC measurements PAAS LB film were performed from room temperature to about 25$0^{\circ}C$ and temperature was increased at the same rate as that of AA LB film. They show that there are TSDC peaks at about 7$0^{\circ}C$ in the arachidic acid LB films, and at about 7$0^{\circ}C$ and 16$0^{\circ}C$ in the PAAs LB films. Results of these measurements indicate the one small peak at 7$0^{\circ}C$ is resulted from a softening of the alkyl group and the large peak at 16$0^{\circ}C$ is possibly due to dipole of C-O group in the PASS molecule. We have calculated the vertical component of the AA and PAAs L film out of the TSDC curves. It shows that the dipole moment of the AA LB film is about 70-mD at 7$0^{\circ}C$. And the dipole moment of PAAS LB film is about 040mD at 7$0^{\circ}C$ and about 200mD at 16$0^{\circ}C$ in the first measurement of TSDC. In the second measurement of TSDC of PASS LB film after cooling down to room temperature, the TSDC peaks are almost disappeared.