A5101450441- Lung Cancer Treatments and Mutations
- HER2/EGFR in Cancer Research
- Cancer Treatment and Pharmacology
- Hormonal Regulation and Hypertension
- Lung Cancer Research Studies
- Blood properties and coagulation
- Cancer therapeutics and mechanisms
- Melanoma and MAPK Pathways
- Chemotherapy-induced organ toxicity mitigation
- Pharmacogenetics and Drug Metabolism
- Cancer Mechanisms and Therapy
- Microbial bioremediation and biosurfactants
- Genomics, phytochemicals, and oxidative stress
- Pituitary Gland Disorders and Treatments
- Adrenal and Paraganglionic Tumors
- Protein Tyrosine Phosphatases
- Mass Spectrometry Techniques and Applications
- Advanced Breast Cancer Therapies
- Cancer, Lipids, and Metabolism
- Angiogenesis and VEGF in Cancer
- Adipose Tissue and Metabolism
- Ferroptosis and cancer prognosis
- Protein Kinase Regulation and GTPase Signaling
- Glutathione Transferases and Polymorphisms
- Microtubule and mitosis dynamics
Yonsei University
2014-2024
Daegu-Gyeongbuk Medical Innovation Foundation
2016-2017
Activation of adiponectin receptors (AdipoRs) by its natural ligand, has been known to be involved in modulating critical metabolic processes such as glucose metabolism and fatty acid oxidation demonstrated a number vitro vivo studies over last two decades. These findings suggest that AdipoRs' agonists could developed into potential therapeutic agent for diseases, diabetes mellitus, especially type II diabetes, long-term disorder characterized high blood sugar, insulin resistance, relative...
Osm1 and Frd1 are soluble fumarate reductases from yeast that critical for allowing survival under anaerobic conditions. Although they maintain redox balance during anaerobiosis, the underlying mechanism is not understood. Here, we report crystal structure of a eukaryotic reductase, which unique among as it lacks heme domain. Structural enzymatic analyses indicate has specific binding pocket flavin molecules, including FAD, FMN, riboflavin, catalyzing their oxidation while reducing to...
Abstract Background and Aims p21‐activated kinase 4 (PAK4), an oncogenic protein, has emerged as a promising target for anticancer drug development. Its role in oxidative stress conditions, however, remains elusive. We investigated the effects of PAK4 signaling on hepatic ischemia/reperfusion (I/R) injury. Approach Results Hepatocyte‐ myeloid‐specific Pak4 knockout (KO) mice their littermate controls were subjected to partial I/R (HIR) manipulated catalytic activity PAK4, either through...
The epidermal growth factor receptor (EGFR), also known as ErbB1 and HER1, belongs to the tyrosine kinase family. EGFR serves primary driver in non-small-cell lung cancer (NSCLC) is a promising therapeutic target for NSCLC. In this study, we synthesized novel chemical library based on benzofuran–indole hybrid scaffold identified 8aa potent selective inhibitor. Interestingly, not only showed anticancer effects against NSCLC cell lines, PC9, A549, but it significant inhibitory double mutant...
Triple-negative breast cancer (TNBC) is an aggressive breast-cancer subtype associated with poor prognosis and high relapse rates. Monopolar spindle 1 kinase (MPS1) apical dual-specificity protein that over-expressed in TNBC. We herein report a highly selective MPS1 inhibitor based on 7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile scaffold. Our lead optimization was guided by key X-ray crystal structure analysis. In vivo evaluation of candidate (9) shown to effectively mitigate human TNBC cell...
We describe the structure‐based design and synthesis of N ‐(2,6‐difluorophenyl)‐3‐(9 H ‐purin‐6‐yl)pyridine‐2‐amine derivatives as a selective pan‐ RAF kinase inhibitor. The synthesized compounds showed highly potent specific inhibition BRAF V600E mutant cell line. Among them, ‐(3‐((3‐(9 ‐purin‐6‐yl)pyridine‐2‐yl)amino)‐2,4‐difluorophenyl)furan‐3‐sulfonamide ( 4b ) exhibited most inhibitory activities against protein enzymes , WT CRAF IC 50 2, 1 nM respectively) line bearing mutation, A375P GI 7 ).
Transglutaminase 2 is a calcium-dependent multi-func tional protein that catalyzes the formation of Ne-(户glutamyl)lysine isopeptide bond between lysine and glutamine residues.1 induces Nuclear Factor-kB (NF-kB) activation through polymerization I-kBo, which results in anti-apoptotic cellular function.2,3It highly associated with inflammatory diseases various cancers.4,5Recently, three types missense mutations (M330R, 1331N, N333S) transglutaminase were found patients early-onset type...
Abstract Genomic insertions within exon20 of both epidermal growth factor receptor (EGFR) and human 2 (HER2) are oncogenic drivers most commonly found in non-small cell lung cancer (NSCLC) but also occurring multiple other tumor types. Exon20 render the receptors resistant to currently approved inhibitors, giving patients with tumors harboring such a worse prognosis than activating EGFR mutations. Moreover, approximately one-third insertion mutations may develop central nervous system (CNS)...
Abstract There are many cell cycle regulating kinases such as CDKs, Polo, Aurora, Bub, NEK/NimA, etc. Dual specificity protein kinase, MPS1(TTK) is one of them. The role MPS1 to regulate spindle assembly checkpoint(SAC) during mitosis. inhibition activity causes death by premature mitotic exit. Some inhibitors (NMS-P153, BOS-172722, CFI-402257, BAY-1217389, and BAY-1161909) in clinical trials. These compounds treated for solid tumors with or without Paclitaxel. We discovered new orally...
Abstract Introduction: Signal transduction in the Ras-Raf-MEK-ERK (MAPK) pathway plays a key role cell survival, growth and proliferation. The is controlled by extracellular signals through receptor tyrosine kinases (RTK) activated oncogenic mutations many types of cancer. B-Raf mutants are found various cancers, such as melanoma, colorectal, ovarian, prostate Ras also carcinomas including colon cancer, pancreatic non-small-cell lung liver mutated K-Ras gene sends continuous to colorectal...
E-mail: skahn@incheon.ac.krReceived March 21, 2012, Accepted April 23, 2012The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme is involved in modulation of glucocorti-coid activity within target tissues. This may contribute to obesity and/or metabolic disease through itsaction adipose or liver tissue. Inhibition 11β-HSD1 has major therapeutic potential for glucocorticoid-associated diseases, including obesity, diabetes (wound healing), and muscle atrophy. To develop such...
Abstract Introduction: The B-Raf, one of serine/threonine kinase, is related to the Ras-Raf-MEK-ERK (MAPK) signal transduction. signaling pathway plays a key role in cell survival, growth and proliferation. B-Raf mutants are found various cancer patients, such as melanoma, papillary thyroid, cisplatin-refractory testicular cancer, colorectal, ovarian, prostate cancer. Especially, over 90% detected mutations V600E which leads constitutive kinase activity 500-fold greater than wild type...
Abstract The third generation EGFR tyrosine kinase inhibitors (TKIs), like Osimertinib, target classical activating mutations containing T790M resistance mutation. However, the exon 20 insertion (Ex20Ins), most common in entire NSCLC, still lacks its therapeutic option. Recently, Robichaux JP et al., showed that Poziotinib, which had been developed as a second-generation TKI, efficacy for and Her2 Ex20Ins compared to T790M. Here, we inhibitors, structurally distinct from both Poziotinib...
There are many cell cycle regulating kinases such as CDKs, Polo, Aurora, Bub, NEK/NimA, etc. Dual specificity protein kinase, MPS1(TTK) is one of them. The role MPS1 to regulate spindle assembly checkpoint(SAC) during mitosis. inhibition activity causes death by premature mitotic exit. Some inhibitors (NMS-P153, BOS-172722, CFI-402257, BAY-1217389, and BAY-1161909) in clinical trials. These compounds treated for solid tumors with or without Paclitaxel. We discovered new orally available...
Abstract Human epidermal growth factor receptor 2 (HER2) amplification is one of oncogenic drivers most found in breast cancer but also occurs multiple other tumor types. Approximately 10-30% patients with develop brain metastases (BCBM), a devastating cause morbidity and mortality. To address this unmet medical need, VRN10s, penetrant, orally bioavailable, irreversible small molecule inhibitors were designed to target HER2 while sparing EGFR wild type. In biochemical assays VRN10s had low...
Abstract Amplification of human epidermal growth factor receptor 2 (HER2) is an oncogenic driver found in approximately 25% breast cancer. Despite the arsenal HER2-directed therapies available to patients, more than 50% patients with HER2 amplification eventually develop central nervous system (CNS) metastases over course their disease indicating a clear medical need for brain penetrant this patient population. ORIC-114 penetrant, orally bioavailable, irreversible small molecule inhibitor...