3篇
您的检索式：作者名="TOSHIHIKO NOGAWA"
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| 1 | QSA-R evaluation of the Ch’an Su and related bufadienolides against the colchicines-resistant primary liver carcinoma cell line PLC/PRF/5显示文摘 | Yoshiaki Kamano Ayano Yamashita Toshihiko Nogawa | 2002 | J Med Chem2002，45，： | 1 |
| 2 | Identification of microbial metabolites that accelerate the ubiquitindependent degradation of c-Myc显示文摘Myc belongs to a family of proto-oncogenes that encode transcription factors.The overexpression of c-Myc causes many types of cancers.Recently,we established a system for screening c-Myc inhibitors and identified antimycin A by screening the RIKEN NPDepo chemical library.The specific mechanism of promoting tumor cell metastasis by high c-Myc expression remains to be explained.In this study,we screened approximately 5,600 microbial extracts using this system and identified a broth prepared from Streptomyces sp.RK19-A0402 strongly inhibits c-Myc transcriptional activity.After purification of the hit broth,we identified compounds closely related to the aglycone of cytovaricin and had a structure similar to that of oligomycin A.Similar to oligomycin A,the hit compounds inhibited mitochondrial complex V.The mitochondria dysfunction caused by the compounds induced the production of reactive oxygen species(ROS),and the ROS activated GSK3α/βthat phosphorylated c-Myc for ubiquitination.This study provides a successful screening strategy for identifying natural products as potential c-Myc inhibitors as potential anticancer agents. | ZIYU LIU AKIKO OKANO EMIKO SANADA YUSHI FUTAMURA TOSHIHIKO NOGAWA KOSUKE ISHIKAWA KENTARO SEMBA JIANG LI XIAOMENG LI HIROYUKI OSADA NOBUMOTO WATANABE | 2023 | Oncology Research2023，31，5： | 0 |
| 3 | Identification of a dihydroorotate dehydrogenase inhibitor thatinhibits cancer cell growth by proteomic profiling显示文摘Dihydroorotate dehydrogenase(DHODH)is a central enzyme of the de novo pyrimidine biosynthesis pathway and is a promising drug target for the treatment of cancer and autoimmune diseases.This study presents the identification of a potent DHODH inhibitor by proteomic profiling.Cell-based screening revealed that NPD723,which is reduced to H-006 in cells,strongly induces myeloid differentiation and inhibits cell growth in HL-60 cells.H-006 also suppressed the growth of various cancer cells.Proteomic profiling of NPD723-treated cells in ChemProteoBase showed that NPD723 was clustered with DHODH inhibitors.H-006 potently inhibited human DHODH activity in vitro,whereas NPD723 was approximately 400 times less active than H-006.H-006-induced cell death was rescued by the addition of the DHODH product orotic acid.Moreover,metabolome analysis revealed that H-006 treatment promotes marked accumulation of the DHODH substrate dihydroorotic acid.These results suggest that NPD723 is reduced in cells to its active metabolite H-006,which then targets DHODH and suppresses cancer cell growth.Thus,H-006-related drugs represent a potentially powerful treatment for cancer and other diseases. | MAKOTO KAWATANI HARUMI AONO SAYOKO HIRANUMA TAKESHI SHIMIZU MAKOTO MUROI TOSHIHIKO NOGAWA TOMOKAZU OHISHI SHUN-ICHI OHBA MANABU KAWADA KANAMI YAMAZAKI SHINGO DAN NAOSHI DOHMAE HIROYUKI OSADA | 2023 | Oncology Research2023，31，6： | 0 |
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