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Your search keyword '"Hong Yu"' showing total 15,613 results
Start Over Author "Hong Yu" Publication Type Academic Journals
15,613 results on '"Hong Yu"'

1. Self-improving generative foundation model for synthetic medical image generation and clinical applications

Author

Wang, Jinzhuo, Wang, Kai, Yu, Yunfang, Lu, Yuxing, Xiao, Wenchao, Sun, Zhuo, Liu, Fei, Zou, Zixing, Gao, Yuanxu, Yang, Lei, Zhou, Hong-Yu, Miao, Hanpei, Zhao, Wenting, Huang, Lisha, Zeng, Lingchao, Guo, Rui, Chong, Ieng, Deng, Boyu, Cheng, Linling, Chen, Xiaoniao, Luo, Jing, Zhu, Meng-Hua, Baptista-Hon, Daniel, Monteiro, Olivia, Li, Ming, Ke, Yu, Li, Jiahui, Zeng, Simiao, Guan, Taihua, Zeng, Jin, Xue, Kanmin, Oermann, Eric, Luo, Huiyan, Yin, Yun, Zhang, Kang, and Qu, Jia

Published
2024
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2. Fetal hepatocytes protect the HSPC genome via fetuin-A

Author

Guo, Xiao-Lin, Wang, Yi-Ding, Liu, Yan-Jun, Chu, Lei, Zhu, Hua, Hu, Ye, Wu, Ren-Yan, Xie, Hong-Yu, Yu, Juan, Li, Shui-Ping, Xiong, Zhao-Yang, Li, Ruo-Yan, Ke, Fang, Chen, Lei, Chen, Guo-Qiang, Chen, Liang, Bai, Fan, Enver, Tariq, Li, Guo-Hong, Li, Huai-Fang, and Hong, Deng-Li

Published
2024
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34. N-(3-Methoxyphenyl)-6-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl)pyridin-2-amine is an inhibitor of the FLT3-ITD and BCR-ABL pathways, and potently inhibits FLT3-ITD/D835Y and FLT3-ITD/F691L secondary mutants.

Author

Wang, Xiuqi, DeFilippis, Rosa, Leung, Yuet-Kin, Shah, Neil Pravin, and Li, Hong-Yu

Subjects
AML, BCR-ABL, Cancer, FLT3-ITD, Secondary mutants, Humans, Cell Line, Tumor, Leukemia, Myeloid, Acute, Protein Kinase Inhibitors, Mutation, fms-Like Tyrosine Kinase 3
Abstract

Activating mutations within FLT3 make up 30 % of all newly diagnosed acute myeloid leukemia (AML) cases, with the most common mutation being an internal tandem duplication (FLT3-ITD) in the juxtamembrane region (25 %). Currently, two generations of FLT3 kinase inhibitors have been developed, with three inhibitors clinically approved. However, treatment of FLT3-ITD mutated AML is limited due to the emergence of secondary clinical resistance, caused by multiple mechanism including on-target FLT3 secondary mutations - FLT3-ITD/D835Y and FLT3-ITD/F691L being the most common, as well as the off-target activation of alternative pathways including the BCR-ABL pathway. Through the screening of imidazo[1,2-a]pyridine derivatives, N-(3-methoxyphenyl)-6-(7-(1-methyl-1H-pyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl)pyridin-2-amine (compound 1) was identified as an inhibitor of both the FLT3-ITD and BCR-ABL pathways. Compound 1 potently inhibits clinically related leukemia cell lines driven by FLT3-ITD, FLT3-ITD/D835Y, FLT3-ITD/F691L, or BCR-ABL. Studies indicate that it mediates proapoptotic effects on cells by inhibiting FLT3 and BCR-ABL pathways, and other possible targets. Compound 1 is more potent against FLT3-ITD than BCR-ABL, and it may have other possible targets; however, compound 1 is first step for further optimization for the development of a balanced FLT3-ITD/BCR-ABL dual inhibitor for the treatment of relapsed FLT3-ITD mutated AML with multiple secondary clinical resistant subtypes such as FLT3-ITD/D835Y, FLT3-ITD/F691L, and cells co-expressing FLT3-ITD and BCR-ABL.

Published
2024

35. An imidazo[1,2-a]pyridine-pyridine derivative potently inhibits FLT3-ITD and FLT3-ITD secondary mutants, including gilteritinib-resistant FLT3-ITD/F691L.

Author

Wang, Xiuqi, DeFilippis, Rosa, Weldemichael, Tsigereda, Gunaganti, Naresh, Tran, Phuc, Leung, Yuet-Kin, Shah, Neil Pravin, and Li, Hong-Yu

Subjects
AML, Cancer, FLT3-ITD, Mutation, Humans, Molecular Docking Simulation, Protein Kinase Inhibitors, Mutation, Leukemia, Myeloid, Acute, Pyridines, fms-Like Tyrosine Kinase 3
Abstract

FLT3 activating mutations are detected in approximately 30 % of newly diagnosed acute myeloid leukemia (AML) cases, most commonly consisting of internal tandem duplication (ITD) mutations in the juxtamembrane region. Recently, several FLT3 inhibitors have demonstrated clinical activity and three are currently approved - midostaurin, quizartinib, and gilteritinib. Midostaurin is a first-generation FLT3 inhibitor with minimal activity as monotherapy. Midostaurin lacks selectivity and is only approved by the USFDA for use in combination with other chemotherapy agents. The second-generation inhibitors quizartinib and gilteritinib display improved specificity and selectivity, and have been approved for use as monotherapy. However, their clinical efficacies are limited in part due to the emergence of drug-resistant FLT3 secondary mutations in the tyrosine kinase domain at positions D835 and F691. Therefore, in order to overcome drug resistance and further improve outcomes, new compounds targeting FLT3-ITD with secondary mutants are urgently needed. In this study, through the structural modification of a reported compound Ling-5e, we identified compound 24 as a FLT3 inhibitor that is equally potent against FLT3-ITD and the clinically relevant mutants FLT3-ITD/D835Y, and FLT3-ITD/F691L. Its inhibitory effects were demonstrated in both cell viability assays and western blots analyses. When tested against cell lines lacking activating mutations in FLT3, no non-specific cytotoxicity effect was observed. Interestingly, molecular docking results showed that compound 24 may adopt different binding conformations with FLT3-F691L compared to FLT3, which may explain its retained activity against FLT3-ITD/F691L. In summary, compound 24 has inhibition potency on FLT3 comparable to gilteritinib, but a more balanced inhibition on FLT3 secondary mutations, especially FLT3-ITD/F691L which is gilteritinib resistant. Compound 24 may serve as a promising lead for the drug development of either primary or relapsed AML with FLT3 secondary mutations.

Published
2024

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