714962-05-7Relevant academic research and scientific papers
ALLOSTERIC BCR-ABL PROTEOLYSIS TARGETING CHIMERIC COMPOUNDS
-
Page/Page column 174; 176-177, (2020/10/18)
The present invention includes novel compounds and methods for preventing or treating diseases associated with and/or caused by overexpression and/or uncontrolled activation of a tyrosine kinase in a subject in need thereof. In certain embodiments, the compounds of the present invention include an allosteric tyrosine kinase inhibitor, a linker, and a ubiquitin ligase binder. The methods of the present invention include administering to the subject an pharmaceutically effective amount of at least one compound of the invention.
Expanding the diversity of allosteric Bcr-Abl inhibitors
Deng, Xianming,Okram, Barun,Ding, Qiang,Zhang, Jianming,Choi, Yongmun,Adrián, Francisco J.,Wojciechowski, Amy,Zhang, Guobao,Che, Jianwei,Bursulaya, Badry,Cowan-Jacob, Sandra W.,Rummel, Gabriele,Sim, Taebo,Gray, Nathanael S.
experimental part, p. 6934 - 6946 (2010/12/25)
Inhibition of Bcr-Abl kinase activity by imatinib for the treatment of chronic myeloid leukemia (CML) currently serves as the paradigm for targeting dominant oncogenes with small molecules. We recently reported the discovery of GNF-2 (1) and GNF-5 (2) as selective non-ATP competitive inhibitors of cellular Bcr-Abl kinase activity that target the myristate binding site. Here, we used cell-based structure-activity relationships to guide the optimization and diversification of ligands that are capable of binding to the myristate binding site and rationalize the findings based upon an Abl-compound 1 cocrystal. We elucidate the structure-activity relationships required to obtain potent antiproliferative activity against Bcr-Abl transformed cells and report the discovery of new compounds (5g, 5h, 6a, 14d, and 21j-I) that display improved potency or pharmacological properties. This work demonstrates that a variety of structures can effectively target the Bcr-Abl myristate binding site and provides new leads for developing drugs that can target this binding site.
Differential tumor cytotoxicity compounds and compositions
-
, (2008/06/13)
The invention is directed to novel biaryl derivatives, to the uses of these compounds in various medicinal applications, including the treatment, prevention and control of proliferative diseases such as tumors, and to pharmaceutical compositions comprisin
