Author
Yehua Zhu
Bio: Yehua Zhu is an academic researcher from Nanjing University of Chinese Medicine. The author has contributed to research in topics: Pharmacophore & Virtual screening. The author has an hindex of 3, co-authored 4 publications receiving 59 citations.
Papers
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TL;DR: A series of hybrids bearing 1H-indazol-3-amine and benzohydroxamic acids scaffold with scaffold hopping and molecular hybridization strategies are designed and compound 7j showed the most potent inhibitory activity against HDAC6 with IC50 of 34 nM and exhibited the great inhibitory activities against a human breast cancer cell line MCF-7 withIC50 of 9 μM in vitro.
47 citations
TL;DR: The protocol of virtual screening in identification of novel potential HDAC inhibitors through pharmacophore modeling, 3D-QSAR, molecular docking and molecular dynamics simulation, and results indicated the hit DB03889 with high in silico inhibitory potency was suitable for further experimental analysis.
Abstract: Histone deacetylases (HDACs), a critical family of epigenetic enzymes, has emerged as a promising target for antitumor drugs. Here, we describe our protocol of virtual screening in identification o...
22 citations
TL;DR: Novel scaffolds discovered in the present study can be used for rational design of PP1 inhibitors with high affinity, and were performed to examine the stability of ligand binding modes.
Abstract: Protein phosphatase 1 (PP1) is a critical regulator of several processes, such as muscle contraction, neuronal signaling, glycogen synthesis, and cell proliferation. Dysregulation of PP1 has recent...
7 citations
TL;DR: The annulation of 4-aminoquinolines with acrylates through two consecutive C-H activations catalyzed by Rh(III) is described, and this protocol will provide appealing strategies for the synthesis of fused quinoline heterocycles.
4 citations
TL;DR: In this article , the effectiveness and safety of the mix of levamlodipine besylate and dihydropyridine combined treatment for essential hypertension was investigated in randomized controlled clinical trials.
1 citations
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01 Jan 2010
TL;DR: This work shows that the ensemble-average pairwise backbone RMSD for a microscopic ensemble underlying a typical protein x-ray structure is approximately 1.1 A, under the assumption that the principal contribution to experimental B-factors is conformational variability.
Abstract: Root mean-square deviation (RMSD) after roto-translational least-squares fitting is a measure of global structural similarity of macromolecules used commonly. On the other hand, experimental x-ray B-factors are used frequently to study local structural heterogeneity and dynamics in macromolecules by providing direct information about root mean-square fluctuations (RMSF) that can also be calculated from molecular dynamics simulations. We provide a mathematical derivation showing that, given a set of conservative assumptions, a root mean-square ensemble-average of an all-against-all distribution of pairwise RMSD for a single molecular species, (1/2), is directly related to average B-factors () and (1/2). We show this relationship and explore its limits of validity on a heterogeneous ensemble of structures taken from molecular dynamics simulations of villin headpiece generated using distributed-computing techniques and the Folding@Home cluster. Our results provide a basis for quantifying global structural diversity of macromolecules in crystals directly from x-ray experiments, and we show this on a large set of structures taken from the Protein Data Bank. In particular, we show that the ensemble-average pairwise backbone RMSD for a microscopic ensemble underlying a typical protein x-ray structure is approximately 1.1 A, under the assumption that the principal contribution to experimental B-factors is conformational variability.
146 citations
TL;DR: This review describes potential applications of chimeric HDAC inhibitors, which simultaneously modulate not only HDAC but also multiple targets, in treatment of relapsing and drug‐resistant cancers.
Abstract: Recently, molecular hybridization paradigm became an interesting and smart way to defeat the multifaceted cancer disease by a single molecular entity that acts via several mechanisms just like a magic bullet. Also, HDAC is an important epigenetic target in drug discovery, and the HDAC inhibitors showed successful pattern as cytotoxic agents. Because of their flexible structure activity relationship, it was easy to link them to other anticancer scaffolds. So, many dual action HDAC inhibitors have been developed and most of these hybrids have higher potency than the constituting parents in fighting of the cancer cells. This review describes potential applications of chimeric HDAC inhibitors, which simultaneously modulate not only HDAC but also multiple targets, in treatment of relapsing and drug-resistant cancers. We have nearly collected most of the reported dual action HDAC inhibitors yet to provide a comprehensive guide for the drug discovery process for developing more efficient anticancer agents.
100 citations
TL;DR: Interestingly, the selectivity to form the fused or spiro compounds could be switched by resorting to different additives, and the notable features of this protocol include simple substrates and excellent atom economy and regioselectivity.
88 citations
TL;DR: The current method utilizes the radical acceptability of 2 H-indazoles, discovering an ambient temperature reaction to provide facile access to a diverse array of 3-acyl-2 H-Indazoles with three points of structural diversification in 25%-83% yields.
86 citations
10 Oct 2019
TL;DR: This paper examined whether standard theories of differences between Canada and the United States (U.S.) can explain disparities in critical social and political outcomes in the two countries, and found that the U.S. results in the northern tier of states usually resemble those in neighboring Canada more closely than they do in the rest of the country.
Abstract: This chapter asks whether standard theories of differences between Canada and the United States (U.S.) can explain disparities in critical social and political outcomes in the two countries. On six measures of system performance (homicides, infant mortality, poverty, economic inequality, voter turnout, and women legislators) Canada consistently delivers far better outcomes than the U.S., but examination of subnational variation reveals a more complex pattern. Most indicators differ more among U.S. states than among Canadian provinces. Within the U.S., outcomes in the northern tier of states usually resemble those in neighboring Canada more closely than they do the rest of the U.S., especially the South, which performs worst by every measure. Standard institutional and cultural theories of differences between the countries cannot explain regional variation within the U.S. nor the similarity of Northern Border states to Canada. Although obvious differences between Canadian and U.S. political institutions help account for greater homogeneity among provinces, explaining the overall pattern may require invoking such causes as climate, ethnic diversity, size of political units, and subnational political cultures.
78 citations