- Pyrazolylamine Derivatives Reveal the Conformational Switching between Type i and Type II Binding Modes of Anaplastic Lymphoma Kinase (ALK)
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Most anaplastic lymphoma kinase (ALK) inhibitors adopt a type I binding mode, but only limited type II ALK structural studies are available. Herein, we present the structure of ALK in complex with N1-(3-4-[([5-(tert-butyl)-3-isoxazolyl]aminocarbonyl)amino
- Tu, Chih-Hsiang,Lin, Wen-Hsing,Peng, Yi-Hui,Hsu, Tsu,Wu, Jian-Sung,Chang, Chun-Yu,Lu, Cheng-Tai,Lyu, Ping-Chiang,Shih, Chuan,Jiaang, Weir-Torn,Wu, Su-Ying
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p. 3906 - 3919
(2016/05/24)
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- Discovery of 3-phenyl-1H-5-pyrazolylamine derivatives containing a urea pharmacophore as potent and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3)
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Preclinical investigations and early clinical trials suggest that FLT3 inhibitors are a viable therapy for acute myeloid leukemia. However, early clinical data have been underwhelming due to incomplete inhibition of FLT3. We have developed 3-phenyl-1H-5-p
- Lin, Wen-Hsing,Hsu, John T.-A.,Hsieh, Shu-Yi,Chen, Chiung-Tong,Song, Jen-Shin,Yen, Shih-Chieh,Hsu, Tsu,Lu, Cheng-Tai,Chen, Chun-Hwa,Chou, Ling-Hui,Yang, Yung-Ning,Chiu, Ching-Hui,Chen, Ching-Ping,Tseng, Ya-Ju,Yen, Kuei-Jung,Yeh, Ching-Fang,Chao, Yu-Sheng,Yeh, Teng-Kuang,Jiaang, Weir-Torn
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p. 2856 - 2867
(2013/06/27)
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- 3-Phenyl-1H-5-pyrazolylamine-based derivatives as potent and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3)
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A new class of FLT3 inhibitors has been identified based on the 3-phenyl-1H-5-pyrazolylamine scaffold. The structure-activity relationships led to the discovery of two carbamate series, and some potent compounds within these two series exhibited better gr
- Hsu, John T.-A.,Yeh, Teng-Kuang,Yen, Shih-Chieh,Chen, Chiung-Tong,Hsieh, Shu-Yi,Hsu, Tsu,Lu, Cheng-Tai,Chen, Chun-Hwa,Chou, Ling-Hui,Chiu, Ching-Hui,Chang, Yun-I,Tseng, Ya-Ju,Yen, Kuei-Rong,Chao, Yu-Sheng,Lin, Wen-Hsing,Jiaang, Weir-Torn
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p. 4654 - 4659
(2012/08/07)
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- PYRAZOLE COMPOUNDS AND THIAZOLE COMPOUNDS AS PROTEIN KINASES INHIBITORS
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A compound of formula (I): wherein A, B, D, X, Y, R1, R2, R3, m, p, and q are defined herein. Also disclosed is a method for inhibiting FMS-like tyrosine kinase 3, aurora kinase, or vascular endothelial growth factor receptor.
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Paragraph 0062; 0064
(2013/03/26)
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- Discovery and evaluation of 3-phenyl-1H-5-pyrazolylamine-based derivatives as potent, selective and efficacious inhibitors of FMS-like tyrosine kinase-3 (FLT3)
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Preclinical investigations and early clinical trial studies suggest that FLT3 inhibitors offer a viable therapy for acute myeloid leukemia. However, early clinical data for direct FLT3 inhibitors provided only modest results because of the failure to fully inhibit FLT3. We have designed and synthesized a novel class of 3-phenyl-1H-5-pyrazolylamine-derived compounds as FLT3 inhibitors which exhibit potent FLT3 inhibition and high selectivity toward different receptor tyrosine kinases. The structure-activity relationships led to the discovery of two series of FLT3 inhibitors, and some potent compounds within these two series exhibited comparable potency to FLT3 inhibitors sorafenib (3) and ABT-869 (4) in both wt-FLT3 enzyme inhibition and FLT3-ITD inhibition on cell growth (MOLM-13 and MV4;11 cells). In particular, the selected compound 12a exhibited the ability to regress tumors in mouse xenograft models using MOLM-13 and MV4;11 cells.
- Lin, Wen-Hsing,Hsieh, Shu-Yi,Yen, Shih-Chieh,Chen, Chiung-Tong,Yeh, Teng-Kuang,Hsu, Tsu,Lu, Cheng-Tai,Chen, Ching-Ping,Chen, Chun-Wha,Chou, Ling-Hui,Huang, Yu-Lin,Cheng, An-Huei,Chang, Yun-I,Tseng, Ya-Ju,Yen, Kuei-Rong,Chao, Yu-Sheng,Hsu, John T.-A.,Jiaang, Weir-Torn
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experimental part
p. 4173 - 4182
(2011/08/06)
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