A5078258941- Microtubule and mitosis dynamics
- Cytokine Signaling Pathways and Interactions
- Cancer therapeutics and mechanisms
- Ubiquitin and proteasome pathways
- Bioactive Compounds and Antitumor Agents
- Synthesis and biological activity
- Glycosylation and Glycoproteins Research
- Microbial Natural Products and Biosynthesis
- Quinazolinone synthesis and applications
- Synthesis and Biological Evaluation
- Synthesis and Biological Activity
- Telomeres, Telomerase, and Senescence
- Tryptophan and brain disorders
- Peptidase Inhibition and Analysis
- Cancer Mechanisms and Therapy
- Cancer-related Molecular Pathways
- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- Cellular transport and secretion
- Click Chemistry and Applications
- Advanced biosensing and bioanalysis techniques
- Stress Responses and Cortisol
- Synthesis and Reactions of Organic Compounds
- Carbohydrate Chemistry and Synthesis
- Monoclonal and Polyclonal Antibodies Research
University of Shizuoka
2016-2025
Osaka University
1998-2021
Nagasaki University
2019
Osaka Medical and Pharmaceutical University
2019
Kumamoto University
2014
Weatherford College
2008
Hokkaido University
2008
Kyowa Kirin (Japan)
1990-2006
Kansai Medical University
1998-2006
Instytut Farmaceutyczny
2001
The signal transducer and activator of transcription 3 (STAT3) is considered to be an attractive therapeutic target for oncology drug development. We identified a N-[2-(1,3,4-oxadiazolyl)]-4-quinolinecarboxamide derivative, STX-0119, as novel STAT3 dimerization inhibitor by virtual screen using customized version the DOCK4 program with crystal structure STAT3. In addition, we used in vitro cell-based assays such luciferase reporter gene assay fluorescence resonance energy transfer-based...
Immune checkpoint inhibitors and adoptive transfer of gene-engineered T cells have emerged as novel therapeutic modalities for hard-to-treat solid tumors; however, many patients are refractory to these immunotherapies, the mechanisms underlying tumor immune resistance not been fully elucidated. By comparing microenvironment inhibition–sensitive –resistant murine tumors, we observed that resistant tumors had low immunogenicity. We identified antigen presentation by CD11b+F4/80+...
Signal transducer and activator of transcription (STAT) 3, a member family DNA-binding molecules, is potential target in the treatment cancer. The highly phosphorylated STAT3 cancer cells contributes to numerous physiological oncogenic signaling pathways. Furthermore, significant association between glioblastoma multiforme stem-like cell (GBM-SC) development maintenance has been demonstrated recent studies. Previously, we reported novel small molecule inhibitor dimerization, STX-0119, as...
The kinesin spindle protein (KSP) is a mitotic involved in the establishment of functional bipolar during cell division. It considered to be an attractive target for cancer chemotherapy with reduced side effects. Based on natural product scaffold-derived fused indole-based inhibitors and known biphenyl-type KSP inhibitors, various carboline carbazole derivatives were synthesized biologically evaluated. β-Carboline lactam-fused exhibited remarkably potent inhibitory activity arrest...
Abstract Glioblastoma multiforme (GBM) is the most common malignant brain tumor with a median survival time about one year. Invasion of GBM cells into normal major cause poor prognosis and requires dynamic reorganization actin cytoskeleton, which includes lamellipodial protrusions, focal adhesions, stress fibers at leading edge GBM. Therefore, we hypothesized that inhibitors polymerization can suppress migration invasion. First, adopted drug repositioning system for screening...
Abstract The Wnt/β-catenin pathway is a well-known oncogenic pathway. Its suppression has long been considered as an important challenge in treating cancer patients. Among colon patients particular, most carry adenomatous polyposis coli (APC) mutation that leads to aberration of To discover the small molecule inhibitors pathway, we conducted high-throughput screening APC-mutant DLD-1 cells using transcriptional reporter assay, which identified selective inhibitor, K-756. K-756 stabilizes...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTThiol-Mediated DNA Alkylation by the Novel Antitumor Antibiotic LeinamycinAkira Asai, Mitsunobu Hara, Shingo Kakita, Yutaka Kanda, Mayumi Yoshida, Hiromitsu Saito, and SaitohView Author Information Tokyo Research Laboratories Kyowa Hakko Kogyo Co., Ltd. 3-6-6, Asahi-machi, Machida-shi, Tokyo, 194 JapanCite this: J. Am. Chem. Soc. 1996, 118, 28, 6802–6803Publication Date (Web):July 17, 1996Publication History Received19 March 1996Published...
Mitotic kinesin spindle protein (KSP) is involved in the assembly of bipolar during cell division. On basis a common 2,3-fused indole substructure within complex frameworks terpendole E and other KSP inhibitors, carbazoles with bulky alkyl group were identified as novel inhibitory scaffold. Additionally, among several naturally occurring growth inhibitors structures, β-carboline alkaloids, harman harmine, showed moderate inhibition KSP.
The natural product belactosin A (1) with a trans-cyclopropane structure is useful prototype compound for developing potent proteasome (core particle, CP) inhibitors. To date, 1 and its analogues are the only CP ligands that bind to both nonprimed S1 pocket as well primed substrate binding channel; however, these molecules harbor high IC50 value of more than μM. We have performed structure–activity relationship studies, thereby elucidating unnatural cis-cyclopropane derivatives exhibit...
Kinesin spindle protein Eg5 is a target for anticancer therapies, and small molecule inhibitors of its ATPase activity have been developed. We herein report the first time crystal structure biochemical studies on motor domain in complex with new type allosteric inhibitor. The biphenyl-type inhibitor PVZB1194 binds to α4/α6 pocket 15 Å from ATP-binding pocket, which differs conventional that bind L5/α2/α3 Eg5. Binding involved neck-linker conformation also causes conformational changes around...
Abstract Immune checkpoint inhibitors (ICIs) such as anti-PD-1 antibodies have broadened the spectrum of cancer therapies. These are under active development, focusing on identifying new targets and developing effective combination In addition to these advancements, novel in vivo systems required evaluate efficacy newly developed ICI Our goal was establish an innovative evaluation system using a animal model replicating interactions between human immune cells tumor cells. We established by...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Novel Property of Duocarmycin and Its Analogs for Covalent Reaction with DNAAkira Asai, Satoru Nagamura, HIromitsu SaitoCite this: J. Am. Chem. Soc. 1994, 116, 10, 4171–4177Publication Date (Print):May 1, 1994Publication History Published online1 May 2002Published inissue 1 1994https://pubs.acs.org/doi/10.1021/ja00089a004https://doi.org/10.1021/ja00089a004research-articleACS PublicationsRequest reuse permissionsArticle...
We have designed, synthesized, and evaluated using physical, chemical biochemical assays various oligonucleotide N3'-->P5' phosphoramidates, as potential telomerase inhibitors. Among the prepared compounds were 2'-deoxy, 2'-hydroxy, 2'-methoxy, 2'-ribo-fluoro, 2'-arabino-fluoro well novel thio-phosphoramidates. The demonstrated sequence specific dose dependent activity with IC50 values in sub-nM to pM concentration range.