Bioorganic and Medicinal Chemistry Letters p. 5956 - 5959 (2016)
Update date:2022-08-29
Topics:
Yasuda, Daisuke
Nakajima, Mao
Yuasa, Akihiro
Obata, Rika
Takahashi, Kyoko
Ohe, Tomoyuki
Ichimura, Yoshinobu
Komatsu, Masaaki
Yamamoto, Masayuki
Imamura, Riyo
Kojima, Hirotatsu
Okabe, Takayoshi
Nagano, Tetsuo
Mashino, Tadahiko
The Keap1-Nrf2 system is involved not only in biological defense but also in malignancy progression and chemoresistance. The ubiquitin-binding protein p62/Sqstm1 (p62), which is highly expressed in several cancers, competes with Nrf2 for Keap1 binding, leading to activation of Nrf2-mediated gene expression and survival of cancer cells. We had previously identified an inhibitor for the Keap1-phosphorylated-p62 (p-p62) protein-protein interaction (PPI), the acetonyl naphthalene derivative K67. In this study, we established facile synthetic routes for K67 and derivatives with various side chains on the C-2 position of naphthalene ring. K67 possessed high selectivity in the inhibition of Keap1-p-p62. Other derivatives showed potent Keap1-Nrf2 and Keap1-p-p62 PPI inhibitory activities, though the selectivity between the two activities was lower than K67.
View MoreQINGDAO HONG JIN CHEMICAL CO.,LTD.
website:http://www.hongjinchem.com
Contact:+86-532-83657313
Address:2ND Building, 8 Shangqing Road, Qingdao, Shandong Province, China.
ChangZhou XiaQing Chemical Co., Ltd.
Contact:+86-519-88721665
Address:3# Hengluo Road, Henglin Town, Changzhou City, Jiangsu Province,China
guide(suzhou) fine materials co. ltd
Contact:0512-80972173
Address:21st Building, No.369 Lushan Rd, New District Suzhou China 215129
Xiamen Kaijia Imp & Exp Co., Ltd.
Contact:86-592-5101177
Address:Room406 Luhui Building No. 65 Haitian Road Huli Xiamen,China.
Hangzhou Showland Technology Co., Ltd.
Contact:86-571-88920516
Address:ROOM2118,NO.553,WENSAN ROAD,HANGZHOU,CHINA
Doi:10.1021/jo01065a028
(1961)Doi:10.1139/v96-014
(1996)Doi:10.1021/jo01105a053
(1958)Doi:10.1016/j.bmcl.2009.01.070
(2009)Doi:10.1016/S0040-4039(00)99929-5
(1984)Doi:10.1080/10426507.2017.1416615
(2018)