| Item type |
デフォルトアイテムタイプ_（フル）(1) |
| 公開日 |
2023-03-18 |
| タイトル |
|
|
タイトル |
Novel Oral Derivative UD-017, a Highly Selective CDK7 Inhibitor, Exhibits Anticancer Activity by Inducing Cell-Cycle Arrest and Apoptosis in Human Colorectal Cancer |
|
言語 |
en |
| 作成者 |
Aga, Yasuhiro
Matsushita, Takashi
Ogi, Sayaka
Onuma, Kazuhiro
Sunamoto, Hidetoshi
Ogawa, Ayumi
Kono, Shigeyuki
Iwase, Noriaki
Tokunaga, Yasunori
Ushiyama, Shigeru
Nara, Futoshi
Konno, Yasushi
Yoshizumi, Masao
Kokubo, Hiroki
Yoneda, Kenji
|
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 権利情報 |
|
|
権利情報 |
Copyright (c) 2020 Hiroshima University Medical Press |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
UD-017 |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
CDK7 inhibitor |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
colorectal cancer |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
HCT-116 |
| 内容記述 |
|
|
内容記述 |
Objective: This study aimed to investigate the anticancer profile of a new cyclin-dependent kinase 7 (CDK7) inhibitor, UD-017, by examining its mechanism of action using HCT-116 colorectal cancer cells. Methods: The anticancer properties of UD-017 were assessed using several assays, including in vitro kinase, proliferation, and apoptosis assays, western blot analysis, and an in vivo xenograft mouse model. Results: UD-017 significantly inhibited CDK7 activity (IC50 = 16 nM) with high selectivity in an in vitro kinase assay testing a panel of over 300 proteins and lipid kinases. UD-017 also inhibited the growth of HCT-116 cells (GI50 = 19 nM) and inhibited the phosphorylation of various downstream mediators of CDK7 signaling. In cell cycle and apoptosis assays using HCT-116 cells, UD-017 increased the number of cells in both G1 and G2/M phases and induced apoptosis. In vivo, UD-017 inhibited tumor growth in an HCT-116 xenograft mouse model by 33%, 64%, and 88% at doses of 25, 50, and 100 mg/kg, respectively, with clear dose-dependency. Co-administration of 5-FU and 50 mg/kg UD-017 had a strong synergistic effect, as reflected in the complete inhibition of tumor growth. Conclusion: CDK7 may play a major role in colorectal cancer growth by regulating the cell cycle and apoptosis. UD-017 is a promising candidate therapeutic agent for the treatment of cancer involving CDK7 signaling. |
|
言語 |
en |
| 出版者 |
|
|
出版者 |
Hiroshima University Medical Press |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
departmental bulletin paper |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 関連情報 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
10.24811/hjms.69.1_23 |
| 関連情報 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.24811/hjms.69.1_23 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
0018-2052 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
2433-7668 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA00664312 |
| 開始ページ |
|
|
開始ページ |
23 |
| 書誌情報 |
Hiroshima Journal of Medical Sciences
Hiroshima Journal of Medical Sciences
巻 69,
号 1,
p. 23-31,
発行日 2020-03
|
| 旧ID |
49106 |
HiroshimaJMedSci_69_23.pdf (1.1 MB)
