A5101565298- Protein Kinase Regulation and GTPase Signaling
- Melanoma and MAPK Pathways
- Histone Deacetylase Inhibitors Research
- Synthesis and biological activity
- NF-κB Signaling Pathways
- Enzyme function and inhibition
- PI3K/AKT/mTOR signaling in cancer
- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Cancer-related gene regulation
- RNA and protein synthesis mechanisms
- Cytokine Signaling Pathways and Interactions
- HER2/EGFR in Cancer Research
- Synthetic Organic Chemistry Methods
- Wnt/β-catenin signaling in development and cancer
- Quinazolinone synthesis and applications
- Signaling Pathways in Disease
- Kruppel-like factors research
- Catalytic C–H Functionalization Methods
- Synthesis and Characterization of Heterocyclic Compounds
- RNA modifications and cancer
- Polyamine Metabolism and Applications
- vaccines and immunoinformatics approaches
- RNA Research and Splicing
- Peptidase Inhibition and Analysis
Yonsei University
2008-2019
Leucyl-tRNA synthetase (LRS) is known to function as leucine sensor in the mammalian target of rapamycin complex 1 (mTORC1) pathway. However, pathophysiological significance its activity not well understood. Here, we demonstrate that for mTORC1 activation LRS can be decoupled from catalytic activity. We identified compounds inhibit leucine-dependent pathway by specifically inhibiting GTPase activating LRS, while affecting For further analysis, selected one compound, BC-LI-0186, which binds...
In light of the anti-inflammatory properties histone deacetylase (HDAC) inhibitors, such as suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), we examined a new HDAC inhibitor KBH-A42 for its activities. showed noteworthy in vitro via suppression production TNF-α, proinflammatory cytokine, nitric oxide (NO), effector molecule, LPS-stimulated RAW264.7 cells peritoneal macrophages. It also inhibited TNF-α vivo demonstrated LPS-induced mouse endotoxemia model. The levels IL-1β,...
Hydroxamate-based HDAC inhibitors have promising anticancer activities but metabolic instability and poor pharmacokinetics leading to in vivo results. QSAR PK studies of showed that a γ-lactam core modified cap group, including halo, alkyl, alkoxy groups with various carbon chain linkers, improved inhibition stability. The biological properties the were evaluated; compound designated 8f had potent activity high oral bioavailability.
Abstract The epidermal growth factor receptor (EGFR) inhibitors such as erlotinib and gefitinib are widely used for treatment of non-small cell lung cancer (NSCLC), but they have shown limited efficacy in an unselected population patients. KRAS mutations, which identified approximately 20% NSCLC patients, to be associated with the resistance EGFR tyrosine kinase (TKIs). Currently, there is no clinically available targeted therapy can effectively inhibit tumors harboring mutations. This study...
Abstract Histone deacetylases (HDACs) are important enzymes in epigenetic regulation and therapeutic targets for cancer. Most zinc‐dependent HDACs induce proliferation, dedifferentiation, anti‐apoptotic effects cancer cells. We designed synthesized a new series of pyridone‐based HDAC inhibitors that have pyridone ring the core structure conjugated system with an olefin connecting hydroxamic acid moiety. Consequently, most selected showed similar or higher inhibition profiles addition to...
Recently, we identified a novel strategy for anticancer chemotherapy by restoring runt-related transcription factor 3 (RUNX3) levels via lactam-based histone deacetylase (HDAC) inhibitors that stabilize RUNX3. Described here are the synthesis, biological evaluation, and pharmacokinetic evaluation of new synthetic small molecules based on pyridone-based HDAC specifically RUNX3 acetylation regulate its function. Many newly synthesized compounds showed favorable RUNX activities, inhibitory...
5075 Background: Ovarian cancer continues to be the leading cause of mortality from gynecological malignancy despite advancements in novel therapeutics. Our group recently demonstrated that C-terminal binding protein 2 (CtBP2) is overexpressed epithelial ovarian carcinoma and alters their response histone deacetylase (HDAC) inhibitors. We designed a study aimed at examining differential gene expression between wild-type CtBP2-knockdown cell lines identify key pathways regulated by CtBP2....