913297-15-1Relevant articles and documents
Discovery of a Potent FLT3 Inhibitor (LT-850-166) with the Capacity of Overcoming a Variety of FLT3 Mutations
Cai, Jiongheng,Chen, Yadong,Chen, Yun,Cheng, Jie,Cheng, Zitian,Heng, Hao,Huang, Fei,Jia, Kun,Li, Hongmei,Lu, Shuai,Lu, Tao,Ren, Jiwei,Sheng, Tiancheng,Song, Shiyu,Tang, Weifang,Wang, Zhijie,Wu, Yingli,Zhu, Yifan
, p. 14664 - 14701 (2021/10/12)
Secondary mutations of FLT3 have become the main mechanism of FLT3 inhibitor resistance that presents a significant clinical challenge. Herein, a series of pyrazole-3-amine derivatives were synthesized and optimized to overcome the common secondary resistance mutations of FLT3. The structure-activity relationship and molecular dynamics simulation studies illustrated that the ribose region of FLT3 could be occupied to help address the obstacle of secondary mutations. Among those derivatives, compound 67 exhibited potent and selective inhibitory activities against FLT3-ITD-positive acute myeloid leukemia (AML) cells and possessed equivalent potency against transformed BaF3 cells with a variety of secondary mutations. Besides, cellular mechanism assays demonstrated that 67 strongly inhibited phosphorylation of FLT3 and its downstream signaling factors, as well as induced cell cycle arrest and apoptosis in MV4-11 cells. In the MV4-11 xenograft models, 67 exhibited potent antitumor potency without obvious toxicity. Taken together, these results demonstrated that 67 might be a drug candidate for the treatment of FLT3-ITD-positive AML.
BENZIMIDAZOLE DERIVATIVES AS BROMODOMAIN INHIBITORS
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Paragraph 1102; 1103, (2014/11/27)
This application relates to chemical compounds which may act as inhibitors of; or which may otherwise modulate the activity of, a bromodomain-containing protein, including bromodomain-containing protein 4 (BRD4), and to compositions and formulations containing such compounds, and methods of using and making such compounds. Compounds include compounds of Formula (I) wherein R1a, R1b, R2, R2b, R3, R4a, R4b, and R5 are described herein.
THIAZOLE DERIVATIVES AS PROTEIN KINASE INHIBITORS
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Page/Page column 86, (2009/06/27)
The present invention relates to novel Thiazole Derivatives, compositions comprising the Thiazole Derivatives, and methods for using the Thiazole Derivatives for treating or preventing a proliferative disorder, an anti-proliferative disorder, inflammation, arthritis, a central nervous system disorder, a cardiovascular disease, alopecia, a neuronal disease, an ischemic injury, a viral infection, a fungal infection, or a disorder related to the activity of a protein kinase.