A5059170589- Cancer-related gene regulation
- Wnt/β-catenin signaling in development and cancer
- Crystallization and Solubility Studies
- Chemical Synthesis and Analysis
- HER2/EGFR in Cancer Research
- X-ray Diffraction in Crystallography
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Microbial Natural Products and Biosynthesis
- Monoclonal and Polyclonal Antibodies Research
- 14-3-3 protein interactions
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Asthma and respiratory diseases
- Weed Control and Herbicide Applications
- Pesticide and Herbicide Environmental Studies
- Pancreatic and Hepatic Oncology Research
- Chronic Myeloid Leukemia Treatments
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Epigenetics and DNA Methylation
- Apelin-related biomedical research
- Genetics and Neurodevelopmental Disorders
- Regulation of Appetite and Obesity
- Dermatology and Skin Diseases
- Bioinformatics and Genomic Networks
Prism Biolab Corporation (Japan)
2009-2022
Oita University
2017-2022
Prism Clinical Research
2009
Protéomique, Réponse Inflammatoire et Spectrométrie de Masse
2009
Proteogenomics Research Institute for Systems Medicine
2009
Asahi Kasei (Japan)
2006-2007
Asahi Kasei (United States)
2004
University of Washington
2004
Kumiai Chemical Industry (Japan)
1990
Kobe University
1988-1989
2501 Background: PRI-724 is a first-in-class modulator of Wnt signaling that inhibits the CREB binding protein and β-catenin interaction. In pre-clinical models, (active metabolite C82) increases p300/β-catenin promotes stem cell differentiation thereby eliminating tumor initiating cells increasing sensitivity to cytotoxic or targeted drugs. Methods: was given as continuous infusion X 7 days q 2 wks. There an initial accelerated dose escalation with one pt per level plan revert 3+3 after 640...
e15721 Background: PRI-724 is a first-in-class small molecule antagonist that inhibits the interaction between β-catenin and its transcriptional coactivator CBP (CREB-binding protein). Preclinical studies of in pancreatic cancer suggest this agent can promote differentiation chemotherapy-insensitive stem cells tumor-initiating cells, inhibit stroma formation, decrease metastatic potential. Methods: Pts with APC, ECOG PS 0-2, measurable disease by RECIST, progression following 1st-line rx...
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...
e15270 Background: PRI-724 is a first-in-class cAMP-response element-binding protein (CBP)/β-catenin modulator that induces stem cell differentiation. In pre-clinical models, increases p300/β-catenin binding and promotes differentiation, eliminating tumor initiating cells increasing sensitivity to cytotoxic drugs. Methods: Patients with APC who progressed following first-line therapy FFX or FX were enrolled. A 3+3 dose escalation design was applied, GEM (1000 mg/m2 of d1,8,15, 28 d cycle),...
Purpose/Aim of the Study: Wnt/β-catenin signaling was reported to be activated in pulmonary fibrosis, and focused on as a target for antifibrotic therapy. However, mechanism how inhibition ameliorate fibrosis has not been fully elucidated. The purpose this study is explore cells examine effect novel inhibitor PRI-724 specifically disrupting interaction β-catenin CBP. Materials Methods: C-82, an active metabolite PRI-724, expression TGF-β1 α-smooth muscle actin (SMA) examined fibroblasts...
Background/Aim: CBP is a transcriptional coactivator in the Wnt/β-catenin pathway that related to cell kinetics and differentiation. This study aimed characterize β-catenin-activated hepatocellular carcinoma (HCC) evaluate direct effects of PRI-724 (a selective inhibitor Wnt/β-catenin/CBP signaling) on HCC. Materials Methods: Immunohistochemistry for β-catenin was performed 199 HCC resected samples. Moreover, using cultured lines, its proteins were analyzed after treatment cells with C-82...
Abstract Endometriosis exhibits unique characteristics, such as fibrosis, resistance to apoptosis, and promotion of cell proliferation; however, its pathophysiology is not fully understood. Recurrence rates after treatment are high, the progression risk continues until menopause; hence, more effective therapy for endometriosis needed. CREB-binding protein (CBP)/β-catenin signaling inhibitors have demonstrated antifibrogenetic effects in liver, lung, skin diseases. The present study evaluated...
Acifluorfen-methyl (AFM) 1μMを暗所で処理したタバコ培養細胞磨砕液は, 光照射下で酸素消費を大きく増加させた. 酸素消費増加と平行して磨砕液中には過酸化脂質が蓄積していた. この酸素消費の増加は, 他のジフェニルエーテルや環状イミド系除草剤にも観察され, 増加量は除草活性と相関が認められた. この現象を解析した結果, 磨砕液中に protoporphyrin IX の蓄積が認められた. そこで tetrapyrrole 合成促進効果を持つ 2,2′-dipyridyl で細胞を処理したところ, 光照射下でAFMと同様の酸素消費増加が観察された. 一方, の蓄積から予想された ferrochelatase の阻害は実験された範囲のジフェニルエーテル系除草剤 (DPE) には認められなかった. これらの事実から 5-amino levulinic acid (ALA) 合成系の促進が疑われ, ALA合成活性の測定を行なった. その結果, AFM処理した細胞は無処理に比べ, ALA合成活性が高く, ALA合成が促進されているものと考えられた. したがって,...
Two molecules with known growth hormone secretagogue (GHS) agonist activity were used as templates to computationally screen approximately 80000 compounds. A total of 108 candidate compounds selected, and five them found be active in the low-micromolar range both cell-based direct binding assays. These structurally diverse significantly differed from GHS agonists. The most compound was subjected SAR evaluation, which slightly increased its potency identified molecular regions important for...
<ns4:p>In a previous Method Article, we have presented the ‘Structure-Activity Relationship (SAR) Matrix’ (SARM) approach. The SARM methodology is designed to systematically extract structurally related compound series from screening or chemical optimization data and organize these associated SAR information in matrices reminiscent of R-group tables. calculations also yield many virtual candidate compounds that form “chemical space envelope” around series. To further extend approach,...
Abstract A novel sp 3 carbon‐rich tricyclic 3D scaffold‐based peptide mimetic compound library was constructed to target protein‐protein interactions. Tricyclic framework 7 synthesized from 9‐azabicyclo[3,3,1]nonan‐3‐one ( 11) via a gold(I)‐catalyzed Conia‐ene reaction. The electron‐donating group on the pendant alkyne of cyclization precursor 12 b – e key forming 6‐ endo ‐ dig cyclized product with complete regioselectivity. Using synthetic strategy for regioselective construction bridged ,...
In a previous Method Article, we have presented the 'Structure-Activity Relationship (SAR) Matrix' (SARM) approach. The SARM methodology is designed to systematically extract structurally related compound series from screening or chemical optimization data and organize these associated SAR information in matrices reminiscent of R-group tables. calculations also yield many virtual candidate compounds that form "chemical space envelope" around series. To further extend approach, different...
Previous studies have shown that intermittent cold stress (ICS) induces depression-like behaviors in mammals. Tupaia belangeri (the tree shrew) is the only experimental animal other than chimpanzee has been to be susceptible infection by hepatitis B and C viruses. Moreover, full genome sequence analysis revealed strong homology between host proteins humans primates. neuromodulator receptor are also known a high degree of with their corresponding primate proteins. Based on these similarities,...
A total of 42 trisubstituted carboranes categorised into five scaffolds were systematically designed and synthesized by exploiting the different reactivities twelve vertices o-, m-, p-carboranes to cover all directions in chemical space. Significant inhibitors hypoxia inducible factor transcriptional activitay mainly observed among scaffold V compounds (e.g., Vi-m, Vo), whereas anti-rabies virus activity was (Va-h), II (IIb-g), IV (IVb) compounds. The pharmacophore model predicted from with...
Mimicking bioactive conformations of peptide segments involved in the formation protein-protein interfaces with small molecules is thought to represent a promising strategy for design interaction (PPI) inhibitors. For compound design, use three-dimensional (3D) scaffolds rich sp3-centers makes it possible precisely mimic conformations. Herein, we introduce DeepCubist, molecular generator designing peptidomimetics based on 3D scaffolds. Firstly, enumerated are superposed target conformation...
The binding of lymphocyte function-associated antigen-1 (LFA-1) to its ligand on endothelial cells, intercellular adhesion molecule-1 (ICAM-1), is a crucial step in the migration leukocytes during early stages inflammation and also involved T-cell activation. In this paper, we report identification series novel antagonists LFA-1/ICAM-1 interaction using ligand-based virtual screening (VS), analogue design, structure-activity relationship (SAR) analysis. Candidate compounds were evaluated...
Krüppel-like factor 5 (KLF5) is a potential target for anticancer drugs. However, as an intrinsically disordered protein (IDP) whose tertiary structure cannot be solved, innovative strategies are needed. We focused on its hydrophobic α-helix structure, defined induced helical motif (IHM), which possible interface protein–protein interaction. Using mathematical analyses predicting the α-helix's and hydrophobicity, 4-amino-acid site (V-A-I-F) was identified IHM. Low-molecular-weight compounds...
The deprotection of the indole (N(ind))-formyl (For) group on Trp was achieved in a 95% yield using N,N'-dimethylethylendiamine (DMEDA) (1.5, 2.0, 3.0 eq) water at room temperature. A new reagent successfully applied to model peptide, H-Phe-Trp(N(ind)-For)-Lys-Tyr-OH, give H-Phe-Trp-Lys-Tyr-OH 91% yield.
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...