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Your search keyword '"Wu, Xiao-ai"' showing total 2 results
Start Over Author "Wu, Xiao-ai" Publisher elsevier science ltd
2 results on '"Wu, Xiao-ai"'

1. Discovery of pyrazolo[1,5-a]pyrimidine-3-carbonitrile derivatives as a new class of histone lysine demethylase 4D (KDM4D) inhibitors.

Author

Fang Z, Wang TQ, Li H, Zhang G, Wu XA, Yang L, Peng YL, Zou J, Li LL, Xiang R, and Yang SY

Subjects
Binding Sites, Drug Evaluation, Preclinical, Humans, Inhibitory Concentration 50, Jumonji Domain-Containing Histone Demethylases metabolism, Molecular Docking Simulation, Nitriles chemical synthesis, Nitriles metabolism, Protein Isoforms antagonists & inhibitors, Protein Isoforms metabolism, Protein Structure, Tertiary, Structure-Activity Relationship, Jumonji Domain-Containing Histone Demethylases antagonists & inhibitors, Nitriles chemistry, Pyrazoles chemistry, Pyrimidines chemistry
Abstract

Herein we report the discovery of a series of new small molecule inhibitors of histone lysine demethylase 4D (KDM4D). Molecular docking was first performed to screen for new KDM4D inhibitors from various chemical databases. Two hit compounds were retrieved. Further structural optimization and structure-activity relationship (SAR) analysis were carried out to the more selective one, compound 2, which led to the discovery of several new KDM4D inhibitors. Among them, compound 10r is the most potent one with an IC 50 value of 0.41±0.03μM against KDM4D. Overall, compound 10r could be taken as a good lead compound for further studies., (Copyright © 2017. Published by Elsevier Ltd.)

Published
2017
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2. Discovery and structure-activity analysis of 4-((5-nitropyrimidin-4-yl)amino)benzimidamide derivatives as novel protein arginine methyltransferase 1 (PRMT1) inhibitors.

Author

Yu XR, Tang Y, Wang WJ, Ji S, Ma S, Zhong L, Zhang CH, Yang J, Wu XA, Fu ZY, Li LL, and Yang SY

Subjects
Amides chemistry, Amides pharmacology, Animals, Binding Sites, Blotting, Western, Cell Line, Tumor, Cell Proliferation drug effects, Enzyme Activation drug effects, Humans, Inhibitory Concentration 50, Molecular Structure, Nitro Compounds chemistry, Nitro Compounds pharmacology, Pyrimidines chemistry, Pyrimidines pharmacology, Structure-Activity Relationship, Benzimidazoles chemistry, Benzimidazoles pharmacology, Drug Discovery, Models, Biological, Protein-Arginine N-Methyltransferases antagonists & inhibitors
Abstract

Despite a potential application of PRMT1 inhibitors in cancer treatment, very few of PRMT1 inhibitors have been reported. To obtain novel potent PRMT1 inhibitors, structure optimizations towards a hit compound, 4-((6-chloro-5-nitropyrimidin-4-yl)amino)benzimidamide, were carried out. A series of 4-((5-nitropyrimidin-4-yl)amino)benzimidamide derivatives were synthesized. Structure-activity relationship analysis led to the discovery of a number of PRMT1 inhibitors. The most potent compound corresponds to compound 6d, which showed an IC50 value of 2.0 μM against PRMT1. This compound also displayed a considerable anti-proliferative activity against three tumor cell lines, DLD-1, T24 and SH-SY-5Y, with IC50 values of 4.4 μM, 13.1 μM and 11.4 μM, respectively., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Published
2015
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