40718-14-7Relevant academic research and scientific papers
Structural development of N-(4-phenoxyphenyl)benzamide derivatives as novel SPAK inhibitors blocking WNK kinase signaling
Fujii, Shinya,Ishigami-Yuasa, Mari,Isobe, Kiyoshi,Kagechika, Hiroyuki,Kikuchi, Eriko,Mori, Takayasu,Suzuyama, Honoka,Uchida, Shinichi,Watanabe, Yuko
supporting information, (2020/07/21)
We report here structural development of N-(4-phenoxyphenyl)benzamide derivatives as novel SPAK (STE20/SPS1-related proline/alanine-rich kinase) inhibitors. Abnormal activation of the signal cascade of with-no-lysine kinase (WNK) with OSR1 (oxidative stress-responsive kinase 1)/SPAK and NCC (NaCl cotransporter) results in characteristic salt-sensitive hypertension, and therefore inhibitors of the WNK-OSR1/SPAK-NCC cascade are candidates for antihypertensive drugs. Based on the structure of lead compound 2, we examined the SAR of N-(4-phenoxyphenyl)benzamide derivatives, and developed compound 20l as a potent SPAK inhibitor. Compounds 20l is a promising candidate for a new class of antihypertensive drugs.
HER2 Kinase-Targeted Breast Cancer Therapy: Design, Synthesis, and in Vitro and in Vivo Evaluation of Novel Lapatinib Congeners as Selective and Potent HER2 Inhibitors with Favorable Metabolic Stability
Elwaie, Tamer A.,Abbas, Safinaz E.,Aly, Enayat I.,George, Riham F.,Ali, Hamdy,Kraiouchkine, Nikolai,Abdelwahed, Khaldoun S.,Fandy, Tamer E.,El Sayed, Khalid A.,Abd Elmageed, Zakaria Y.,Ali, Hamed I.
, p. 15906 - 15945 (2021/01/09)
HER2 kinase as a well-established target for breast cancer (BC) therapy is associated with aggressive clinical outcomes; thus, herein we present structural optimization for HER2-selective targeting. HER2 profiling of the developed derivatives demonstrated
Surmounting the resistance against EGFR inhibitors through the development of thieno[2,3-d]pyrimidine-based dual EGFR/HER2 inhibitors
Milik, Sandra N.,Abdel-Aziz, Amal Kamal,Lasheen, Deena S.,Serya, Rabah A.T.,Minucci, Saverio,Abouzid, Khaled A.M.
supporting information, p. 316 - 336 (2018/06/14)
In light of the emergence of resistance against the currently available EGFR inhibitors, our study focuses on tackling this problem through the development of dual EGFR/HER2 inhibitors with improved enzymatic affinities. Guided by the binding mode of the
Navigating into the binding pockets of the HER family protein kinases: Discovery of novel EGFR inhibitor as antitumor agent
Liu, Wei,Ning, Jin-Feng,Meng, Qing-Wei,Hu, Jing,Zhao, Yan-Bin,Liu, Chao,Cai, Li
, p. 3837 - 3851 (2015/08/06)
The epidermal growth factor receptor (EGFR) family has been validated as a successful antitumor drug target for decades. Known EGFR inhibitors were exposed to distinct drug resistance against the various EGFR mutants within non-small-cell lung cancer (NSC
Targeting EGFR/HER2 tyrosine kinases with a new potent series of 6-substituted 4-anilinoquinazoline hybrids: Design, synthesis, kinase assay, cell-based assay, and molecular docking
Elkamhawy, Ahmed,Farag, Ahmed Karam,Viswanath, Ambily Nath Indu,Bedair, Tarek M.,Leem, Dong Gyu,Lee, Kyung-Tae,Pae, Ae Nim,Roh, Eun Joo
supporting information, p. 5147 - 5154 (2015/11/09)
Coexpression of EGFR and HER2 has been found in many tumors such as breast, ovarian, colon and prostate cancers, with poor prognosis of the patients. Herein, our team has designed and synthesized new eighteen compounds with 6-substituted 4-anilinoquinazol
Design and synthesis of novel human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) dual inhibitors bearing a pyrrolo[3,2-d]pyrimidine scaffold
Ishikawa, Tomoyasu,Seto, Masaki,Banno, Hiroshi,Kawakita, Youichi,Oorui, Mami,Taniguchi, Takahiko,Ohta, Yoshikazu,Tamura, Toshiya,Nakayama, Akiko,Miki, Hiroshi,Kamiguchi, Hidenori,Tanaka, Toshimasa,Habuka, Noriyuki,Sogabe, Satoshi,Yano, Jason,Aertgeerts, Kathleen,Kamiyama, Keiji
experimental part, p. 8030 - 8050 (2012/01/14)
Dual inhibitors of human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) have been investigated for breast, lung, gastric, prostate, and other cancers; one, lapatinib, is currently approved for breast cancer. To develop novel HER2/EGFR dual kinase inhibitors, we designed and synthesized pyrrolo[3,2-d]pyrimidine derivatives capable of fitting into the receptors' ATP binding site. Among the prepared compounds, 34e showed potent HER2 and EGFR (HER1) inhibitory activities as well as tumor growth inhibitory activity. The X-ray cocrystal structures of 34e with both HER2 and EGFR demonstrated that 34e interacts with the expected residues in their respective ATP pockets. Furthermore, reflecting its good oral bioavailability, 34e exhibited potent in vivo efficacy in HER2-overexpressing tumor xenograft models. On the basis of these findings, we report 34e (TAK-285) as a promising candidate for clinical development as a novel HER2/EGFR dual kinase inhibitor.
