A5058302405- Fibroblast Growth Factor Research
- Phagocytosis and Immune Regulation
- Kruppel-like factors research
- Synthetic Organic Chemistry Methods
- Cancer-related gene regulation
- Cancer Treatment and Pharmacology
- HER2/EGFR in Cancer Research
- Advanced Synthetic Organic Chemistry
- Cancer, Hypoxia, and Metabolism
- Wnt/β-catenin signaling in development and cancer
- Asymmetric Synthesis and Catalysis
- Angiogenesis and VEGF in Cancer
- Reproductive tract infections research
- Chemical Synthesis and Analysis
- Protein Tyrosine Phosphatases
- Metastasis and carcinoma case studies
- Epigenetics and DNA Methylation
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- RNA Research and Splicing
- PI3K/AKT/mTOR signaling in cancer
- Eosinophilic Disorders and Syndromes
- Marine Sponges and Natural Products
- 14-3-3 protein interactions
- Spectroscopy and Chemometric Analyses
Eisai (Japan)
2009-2022
JFE Holdings (Japan)
2015
Okayama University of Science
1999-2000
Hokkaido University
1991-1999
Lenvatinib is an oral inhibitor of multiple receptor tyrosine kinases (RTKs) targeting vascular endothelial growth factor (VEGFR1-3), fibroblast (FGFR1-4), platelet α (PDGFR α), RET and KIT. Antiangiogenesis activity lenvatinib in VEGF- FGF-driven angiogenesis models both vitro vivo was determined. Roles tumor vasculature (microvessel density (MVD) pericyte coverage) as biomarkers for were also examined this study.We evaluated antiangiogenesis against proliferation tube formation HUVECs...
Lenvatinib is an oral multikinase inhibitor that selectively inhibits vascular endothelial growth factor (VEGF) receptors 1 to 3 and other proangiogenic oncogenic pathway-related receptor tyrosine kinases. To elucidate the origin of potency lenvatinib in VEGF 2 (VEGFR2) inhibition, we conducted a kinetic interaction analysis with VEGFR2 X-ray crystal structure VEGFR2-lenvatinib complexes. Kinetic revealed had rapid association rate constant relatively slow dissociation complex VEGFR2....
c-Met is the cellular receptor for hepatocyte growth factor (HGF) and known to be dysregulated in various types of human cancers. Activation HGF/c-Met pathway causes tumor progression, invasion, metastasis. Vascular endothelial (VEGF) also as a key molecule progression through induction angiogenesis. Because their roles these pathways provide attractive targets therapeutic intervention. We have generated novel, orally active, small compound, E7050, which inhibits both vascular (VEGFR)-2. In...
Abstract The Wnt/β-catenin signaling pathway plays crucial roles in embryonic development and the of multiple types cancer, its aberrant activation provides cancer cells with escape mechanisms from immune checkpoint inhibitors. E7386, an orally active selective inhibitor interaction between β-catenin CREB binding protein, which is part pathway, disrupts HEK293 adenomatous polyposis coli (APC)-mutated human gastric ECC10 cells. It also inhibited tumor growth xenograft model suppressed polyp...
Almost all cancers show intrinsic and/or evasive resistance to vascular endothelial growth factor ( VEGF ) inhibitors by multiple mechanisms. Serum angiopoietin‐2 (Ang2) level has been proposed as a potential biomarker of inhibitor response in several cancers. From these clinical observations, the Ang2 and Tie2 (its receptor) axis focused on promising target. Here, we novel strategy circumvent combining multi‐tyrosine kinase lenvatinib receptor, fibroblast RET inhibitor) golvatinib (E7050;...
Vascular endothelial growth factor receptor (VEGFR) inhibitors are approved for the treatment of several tumor types; however, some tumors show intrinsic resistance to VEGFR inhibitors, and patients develop acquired these inhibitors. Therefore, a strategy overcome inhibitor is urgently required. Recent reports suggest that activation hepatocyte (HGF) pathway through its cognate receptor, Met, contributes resistance. Here, we explored effect HGF/Met signaling on lenvatinib, inhibitor. In in...
The FGFR signaling pathway has a crucial role in proliferation, survival, and migration of cancer cells, tumor angiogenesis, drug resistance. genetic abnormalities, such as gene fusion, mutation, amplification, have been implicated several types cancer. Therefore, FGFRs are considered potential targets for therapy. E7090 is an orally available selective inhibitor the tyrosine kinase activities FGFR1, -2, -3. In kinetic analyses interaction between FGFR1 kinase, associated more rapidly with...
The C1-C12 part (4) of tedanolide (1) was synthesized starting from methyl (R)-3-hydroxy-2-methylpropionate (11a) via a coupling between the C1-C7 aldehyde (6) and C8-C11 iodoalkene (7a). For synthesis 6, mismatched but highly efficient Sharpless dihydroxylation α, β-unsaturated ester (15) with AD-mix-α successfully applied. Compound 7a using hydrozirconation to alkyne (32).
The C1-C7 fragment (4) of tedanolide (1) was synthesized starting from methyl (R)-3-hydroxy-2-methyl-propionate via a mismatched but highly efficient Sharpless dihydroxylation the α, β-unsaturated ester (6) with AD-mix-α.
The C13-C23 part (5) of tedanolide (1) was synthesized starting from enantiomeric methyl (R)- and (S)-3-hydroxy-2-methylpropionates (8) via coupling between the C13-C17 aldehyde (6) C18-C21 iodoalkene (7).
An efficient and stereoselective synthesis of the C13-C23 part (8) was achieved starting from methyl (R)- (S)-3-hydroxy-2-methylpropionates (9) via coupling C13-C17 aldehyde (6), prepared by Evans asymmetric aldol reaction, with C18-C21 iodoalkene (5b) taking advantage 3,4-dimethoxybenzyl protecting group.
We measured anti-Chlamydia pneumoniae (C. pneumoniae) specific antibody titers by means of a newly-developed enzyme-linked immunosorbent assay (ELISA) method using an anti-C. detection reagent. The clinical usefulness this was hereby evaluated. IgG, IgA and IgM in 418 serum specimens obtained from patients with respiratory tract infections were new ELISA method, the results compared determined for same micro immunofluorescence (Micro-IF) method. showed good correlation coefficients IgM. two...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChiral synthesis of polyketide-derived natural products. 28. Synthesis 16-membered macrolide aglycons, carbonolide A, leuconolides, and maridonolides, via B type compounds by virtue completely stereoselective epoxidation reduction based on the conformational control rings with protecting groupsNoriyuki Nakajima, Kouichi Uoto, Tomohiro Matsushima, Osamu Yonemitsu, Hitoshi Goto, Eiji OsawaCite this: J. Org. Chem. 1990, 55, 4, 1129–1132Publication...
Abstract Carcinogenesis is often accelerated by the aberrant activation of components molecules Wnt signaling pathway, especially, APC and beta-catenin are frequently reported to be mutated in various cancers. Therefore, signal pathway thought one attractive therapeutic targets. PRI-724 generated PRISM Pharma a small molecule inhibitor its transcriptional coactivator CREB binding protein (CBP) thereby specific modulating Wnt/beta-catenin intravenous continuous infusion. Here we firstly...
Abstract Innate and adaptive resistance to cancer therapies, such as chemotherapies, molecularly targeted immune-modulating is a major issue in clinical practice. Subpopulations of tumor cells expressing the receptor tyrosine kinase AXL become enriched after treatment with antimitotic drugs, causing relapse. Elevated expression closely associated drug samples, suggesting that plays pivotal role resistance. Although several molecules inhibitory activity have been developed, none sufficient...
Abstract The fibroblast growth factor (FGF) signaling pathway comprises 18 ligands and 4 FGF receptor subtypes, FGFR1, 2, 3 4, which are known as receptor-type tyrosine kinases corresponding to those ligands. Upon ligand binding, FGFRs activate an array of downstream pathways, such the mitogen activated protein kinase (MAPK) phosphoinositide-3-kinase (PI3K)/Akt pathways. Genetic abnormalities (gene fusion, mutation amplification) cause constitutive activation their play important role in...
Abstract Although vascular endothelial growth factor (VEGF) inhibitors provide significant clinical benefit, they often require dose reductions or even withdrawals due to their severe toxicities. Furthermore, almost all cancers show intrinsic and/or evasive resistance VEGF by multiple mechanisms. Serum angiopoietin-2 (Ang2) level has been proposed as a potential biomarker of inhibitor response in several cancers. Response lenvatinib (E7080; VEGFR1-3 inhibitor) is also reported correlate with...
Abstract Background: Lenvatinib mesilate (lenvatinib) selectively inhibits vascular endothelial growth factor receptors (VEGFR1-3), and other proangiogenic oncogenic pathway-related RTKs including fibroblast (FGFR1-4), the platelet-derived receptor (PDGFR) α, KIT, RET. is currently evaluated in several clinical trials, two phase 3 trials patients with thyroid cancers hepatocellular carcinoma. Recently, lenvatinib achieved primary endpoint a trial differentiated cancer. To gain insight into...