ALK PROTEIN DEGRADATION AGENT AND ANTI-TUMOR APPLICATION THEREOF
作者： Jiang Biao , Kong Ying , Sun Ning , Yang Xiaobao , Qiu Xing
DOI:
关键词: Protein degradation 、 Proteases 、 Anaplastic lymphoma kinase 、 Tyrosine kinase 、 Moiety 、 Chemistry 、 Kinase 、 Linker 、 Ubiquitin 、 Biochemistry
摘要: Disclosed by the present invention are a compound represented formula (I) and an anti-tumor application thereof. The has degrading inhibiting effect on anaplastic lymphoma kinase (ALK)-targeted protein, is mainly composed of four parts: first part, i.e., ALK-tyrosine inhibitors (TKIs), having activity ALK tyrosine kinase; second LIN, different linker; third ubiquitin ligase binding moiety (ULM), small molecule ligand VHL, CRBN or other proteases ubiquitination function; fourth group A, carbonyl default, which covalently binds ALK-TKIs LIN to ULM. series compounds designed synthesized in have wide pharmacological activities, functions proteins activity, may be used for related tumor treatment.
lens.org 参考文章(16)
Axel Wellmann, Victoria Doseeva, Wayne Butscher, Mark Raffeld, Paula Fukushima, Maryalice Stetler‐Stevenson, Kevin Gardner, THE ACTIVATED ANAPLASTIC LYMPHOMA KINASE INCREASES CELLULAR PROLIFERATION AND ONCOGENE UP-REGULATION IN RAT 1A FIBROBLASTS The FASEB Journal. ,vol. 11, pp. 965- 972 ,(1997) , 10.1096/FASEBJ.11.12.9337149
Andrew P. Crew, Craig Crews, Hanqing Dong, Caterina Ferraro, Kam Siu, Jing Wang, Xin Chen, Yimin Qian, Meizhong Jin, Imide-based modulators of proteolysis and associated methods of use ,(2015)
Takashi Fujishita, Massimo Loda, Ross E. Turner, Marinshine Gentler, Tatsuhiko Kashii, Oscar S. Breathnach, Bruce E. Johnson, Sensitivity of Non-Small-Cell Lung Cancer Cell Lines Established from Patients Treated with Prolonged Infusions of Paclitaxel Oncology. ,vol. 64, pp. 399- 406 ,(2003) , 10.1159/000070299
Young Lim Choi, Kengo Takeuchi, Manabu Soda, Kentaro Inamura, Yuki Togashi, Satoko Hatano, Munehiro Enomoto, Toru Hamada, Hidenori Haruta, Hideki Watanabe, Kentaro Kurashina, Hisashi Hatanaka, Toshihide Ueno, Shuji Takada, Yoshihiro Yamashita, Yukihiko Sugiyama, Yuichi Ishikawa, Hiroyuki Mano, Identification of Novel Isoforms of the EML4-ALK Transforming Gene in Non–Small Cell Lung Cancer Cancer Research. ,vol. 68, pp. 4971- 4976 ,(2008) , 10.1158/0008-5472.CAN-07-6158
Manabu Soda, Young Lim Choi, Munehiro Enomoto, Shuji Takada, Yoshihiro Yamashita, Shunpei Ishikawa, Shin-ichiro Fujiwara, Hideki Watanabe, Kentaro Kurashina, Hisashi Hatanaka, Masashi Bando, Shoji Ohno, Yuichi Ishikawa, Hiroyuki Aburatani, Toshiro Niki, Yasunori Sohara, Yukihiko Sugiyama, Hiroyuki Mano, None, Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer Nature. ,vol. 448, pp. 561- 566 ,(2007) , 10.1038/NATURE05945
Y. S. Ju, W.-C. Lee, J.-Y. Shin, S. Lee, T. Bleazard, J.-K. Won, Y. T. Kim, J.-I. Kim, J.-H. Kang, J.-S. Seo, A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing Genome Research. ,vol. 22, pp. 436- 445 ,(2012) , 10.1101/GR.133645.111
Kengo Takeuchi, Young Lim Choi, Yuki Togashi, Manabu Soda, Satoko Hatano, Kentaro Inamura, Shuji Takada, Toshihide Ueno, Yoshihiro Yamashita, Yukitoshi Satoh, Sakae Okumura, Ken Nakagawa, Yuichi Ishikawa, Hiroyuki Mano, KIF5B-ALK, a Novel Fusion Oncokinase Identified by an Immunohistochemistry-based Diagnostic System for ALK-positive Lung Cancer Clinical Cancer Research. ,vol. 15, pp. 3143- 3149 ,(2009) , 10.1158/1078-0432.CCR-08-3248
I. Dagogo-Jack, A.T. Shaw, Crizotinib resistance: implications for therapeutic strategies. Annals of Oncology. ,vol. 27, pp. 50- ,(2016) , 10.1093/ANNONC/MDW305
Yoon Jin Cha, Hye Ryun Kim, Hyo Sup Shim, Clinical outcomes in ALK-rearranged lung adenocarcinomas according to ALK fusion variants Journal of Translational Medicine. ,vol. 14, pp. 296- 296 ,(2016) , 10.1186/S12967-016-1061-Z
Shinsuke Kitahara, Yasushi Goto, Hidehito Horinouchi, Shintaro Kanda, Hiroshi Nokihara, Noboru Yamamoto, Kazuhisa Takahashi, Yuichiro Ohe, Tetsuhiko Asao, Yutaka Fujiwara, Kota Itahashi, Sequential Use of Anaplastic Lymphoma Kinase Inhibitors in Japanese Patients With ALK-Rearranged Non-Small-Cell Lung Cancer: A Retrospective Analysis. Clinical Lung Cancer. ,vol. 18, ,(2017) , 10.1016/J.CLLC.2016.11.015