• Molecules and Cells
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• v.26 no.4
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• pp.380-386
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• 2008

During embryonic and cancer development, the Hedgehog family of proteins, including Sonic Hedgehog, play an important role by relieving the inhibition of Smo by Ptc, thus activating the Smo signaling cascade. Recently, a purine compound, purmorphamine, has been reported to target the Hedgehog signaling pathway by interacting with Smo. Interestingly, both Sonic Hedgehog and purmorphamine were found to promote the osteogenic differentiation of mouse chondroprogenitor cells. However, there is insufficient information as to how the activation of this seemingly unrelated signaling pathway, either by Sonic Hedgehog or purmorphamine, contributes to osteogenesis. Using alkaline phosphatase assays, we screened 125 purmorphamine derivatives from the Korea Chemical Bank for effects on the differentiation of preosteoblast C2C12 cells. Here, we report that two purine derivatives modulate ALP activity as well as the expression of genes whose expression is known or suggested to be involved in osteogenesis.

• Genomics & Informatics
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• v.8 no.4
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• pp.177-184
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• 2010

The target of rapamycin (TOR) signaling pathway is a conserved pathway that regulates eukaryotic cell growth in response to environmental cues. Chemical genomic approaches that profile rapamycin sensitivity of yeast deletion strains have given insights into the function of TOR signaling pathway. In the present study, we analyzed the rapamycin sensitivity of yeast deletion library strains on synthetic medium. As a result, we identified 130 strains that are hypersensitive or resistant to rapamycin compared with wild-type cells. Among them, 36 genes are newly identified to be related to rapamycin sensitivity. Moreover, we found 16 strains that show alteration in rapamycin sensitivity between complex and synthetic media. We suggest that these genes may be involved in part of TOR signaling activities that is differentially regulated by media composition.

• Molecules and Cells
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• v.45 no.7
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• pp.435-443
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• 2022

In response to environmental changes, signaling pathways rewire gene expression programs through transcription factors. Epigenetic modification of the transcribed RNA can be another layer of gene expression regulation. N⁶-adenosine methylation (m⁶A) is one of the most common modifications on mRNA. It is a reversible chemical mark catalyzed by the enzymes that deposit and remove methyl groups. m⁶A recruits effector proteins that determine the fate of mRNAs through changes in splicing, cellular localization, stability, and translation efficiency. Emerging evidence shows that key signal transduction pathways including TGFβ (transforming growth factor-β), ERK (extracellular signal-regulated kinase), and mTORC1 (mechanistic target of rapamycin complex 1) regulate downstream gene expression through m⁶A processing. Conversely, m⁶A can modulate the activity of signal transduction networks via m⁶A modification of signaling pathway genes or by acting as a ligand for receptors. In this review, we discuss the current understanding of the crosstalk between m⁶A and signaling pathways and its implication for biological systems.

• BMB Reports
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• v.43 no.11
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• pp.711-719
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• 2010

Kinomics is an emerging and promising approach for deciphering kinomes. Chemical kinomics is a discipline of chemical genomics that is also referred to as "chemogenomics", which is derived from chemistry and biology. Chemical kinomics has become a powerful approach to decipher complicated phosphorylation-based cellular signaling networks with the aid of small molecules that modulate kinase functions. Moreover, chemical kinomics has played a pivotal role in the field of kinase drug discovery as it enables identification of new molecular targets of small molecule kinase modulators and/or exploitation of novel functions of known kinases and has also provided novel chemical entities as hit/lead compounds. In this short review, contemporary chemical kinomics technologies such as activity-based protein profiling, T7 kinasetagged phages, kinobeads, three-hybrid systems, fluorescenttagged kinase binding assays, and chemical genomic profiling are discussed along with a novel allosteric Bcr-Abl kinase inhibitor (GNF-2/GNF-5) as a successful application of chemical kinomics approaches.

• Korean Journal of Agricultural Science
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• v.45 no.3
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• pp.365-378
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• 2018

Anthracnose caused by Colletotrichum gloeosporioides, which is one of the major diseases of red dates, causes severe damages in jujube (Zizyphus jujuba Miller) production in Korea. This study was done to evaluate the inhibition of anthracnose occurrence and pathogen growth by the treatment of environment-friendly materials such as a Bordeaux mixture and loess-sulfur mixture and by defense-response signaling in jujube. The in vitro test of the environment-friendly materials and signaling molecules that were routinely applied did not exhibit any antifungal activities against the pathogen for jujube anthracnose. The Bordeaux mixture and loess-sulfur mixture at a two-fold concentration showed inhibition zones that were 16.0 and 20.3 mm in diameter, respectively. In the pathogen inoculation test with detached jujube tree leaves, while treatment with the environment-friendly materials diluted by half showed no inhibition of lesion development, they did show inhibition of lesion development when they were routinely applied to the leaves. In detached jujube fruits inoculated with the pathogen, better suppressive effects by the treatment of the environment-friendly materials were seen in the fruits at a young stage rather than in the ripening stage. The in vivo test with jujube trees in pots showed that the treatment of salicylic acid (1 mM) resulted in the best suppressive effects against lesion development. The results suggest that it is possible to manage the incidence of anthracnose by the treatment of environment-friendly materials such as the Bordeaux and loess-sulfur mixtures and signaling chemicals such as ethephon, hydrogen peroxide, methyl jasmonate, and salicylic acid in jujube trees and fruits. Consequently, these findings suggest that environment-friendly materials and defense response signaling molecules could be used as suitable candidates for sustainable agrochemicals to manage anthracnose in jujube production.

• Bulletin of the Korean Chemical Society
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• v.32 no.4
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• pp.1228-1230
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• 2011

A new amine receptor 2 utilizing anthracene and nitrophenyl group as signaling group was designed and synthesized. The receptor 2 only utilizes four amine N-H's and 9-anthracenyl hydrogen to bind anions. The receptor 2 can bind anions through hydrogen bonds with a selectivity of $CH_3CO_2^-$ > $H_2PO_4^-$ > $F^-$ > $C_6H_5CO_2^-$ > $Cl^-$ in highly polar solvent such as DMSO without protonation of amine.

• Bulletin of the Korean Chemical Society
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• v.34 no.11
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• pp.3345-3349
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• 2013

Hsp90 shows great promise as a therapeutic target due to its potential to disable multiple signaling pathways simultaneously. In this study, we discovered that a natural product, butein moderately inhibited the growth of drug-resistant cancer cells (A2780cis and H1975), and brought about the degradation of oncogenic Hsp90 client proteins. The study demonstrated that butein would be a therapeutic lead to circumvent drug-resistance in cancer chemotherapy. The structure-based screening, synthesis, and biological evaluation of butein are described herein.

• Bulletin of the Korean Chemical Society
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• v.30 no.12
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• pp.3031-3033
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• 2009

A new colorimetric anion sensor 1 has been synthesized based on both Fat brown RR dye and a nitrophenyl group. This new receptor 1 could recognize the presence of fluoride ion effectively and selectively by the change of color of solution. In addition, receptor 1 shows higher affinity for acetate, dihydrogenphosphate, and hydrogensulfate than the other anions such as chloride, bromide, iodide, perchlorate, and nitrate in acetonitrile.

• Bulletin of the Korean Chemical Society
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• v.26 no.10
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• pp.1555-1559
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• 2005

High-performance fluorescent probes which exhibit either on/off or dual color fluorescence switching in response to the presence of organic vapors with a rapid response, a high sensitivity and a high-contrast on/off signaling ratio were demonstrated on the basis of the vapor-controlled AIEE phenomenon.

• Oncology Letters
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• v.17 no.3
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• pp.3589-3598
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• 2019

Colorectal cancer (CRC) is a complex disease involving numerous genetic abnormalities. One of the major characteristics of CRC is enhanced Wnt signaling caused by loss-of-function mutations in the adenomatous polyposis coli (APC) gene. Previously, it has been demonstrated that the majority of malignant phenotypes following APC deletion in adult murine small intestines could be rescued when Myc, a downstream target of the Wnt pathway, was deleted. This indicated that Myc is a critical regulator of CRC development following APC loss. Previous studies reported that cyclic adenosine 3',5'-monophosphate (cAMP) can influence the AKT/mammalian target of rapamycin (mTOR) survival pathway in cancer and Myc is a critical downstream molecule of AKT/mTOR signaling. Phosphodiesterase 4D (PDE4D), a member of the cAMP-specific PDE4 family, has been associated with drug resistance in CRC. However, the association between PDE4D and Myc remains unclear. To investigate the potential role of PDE4D in Myc regulation in CRC, the present study evaluated the expression levels of PDE4 subtypes in DLD-1 CRC cells. Additionally, the effects of PDE4 inhibitors on Myc expression and oncogenic properties were analyzed by western blot analysis, reverse transcription-quantitative polymerase chain reaction, colony formation and soft agar assays. It was demonstrated that cAMP/PDE4D signals serve a critical role in regulating Myc expression in DLD-1 CRC cells. Furthermore, PDE4D was identified to be a main hydrolyzer of cAMP and suppression of PDE4D using selective inhibitors of PDE4 increased intracellular cAMP levels, which resulted in a marked decrease in the oncogenic properties of DLD-1 cells, including colony formation, cell proliferation and anchorage-independent growth. Notably, the current data imply that cAMP represses Myc expression via the downregulation of AKT/mTOR signaling, which was abolished by high PDE4D activities in DLD-1 cells. Additionally, a natural polyphenol resveratrol in combination with forskolin elevated the concentration of cAMP and enhanced the expression of Myc and the malignant phenotype of DLD-1 cells, reproducing the effect of known chemical inhibitors of PDE4. In conclusion, the present study identified that cAMP/PDE4D signaling is a critical regulator of Myc expression in DLD-1 and possibly other CRC cells.