Discovery of Novel Mesangial Cell Proliferation Inhibitors Using a Three-Dimensional Database Searching Method

Kurogi, Yasuhisa; Miyata, Kazuyoshi; Okamura, Takashi; Hashimoto, Kinji; Tsutsumi, Kazuhiko; Nasu, Masahiro; Moriyasu, Matsuko

doi:10.1021/jm010060v

Cited by 34 publications

(23 citation statements)

References 16 publications

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“…Secondly, Ibrolipim has been proved to be highly effective in increasing plasma HDL-C through mediating reverse cholesterol transport from peripheral tissues to the liver to protect against the excessive accumulation of cholesterol [44]. Thirdly, Ibrolipim exhibits the significant inhibitory activity of in vitro mesangial cell proliferation [45]. Further studies are warranted to determine the mechanisms of Ibrolipim in the suppression of renal lipid accumulation and renal disease.…”

Section: Discussionmentioning

confidence: 99%

Preventive effect of Ibrolipim on suppressing lipid accumulation and increasing lipoprotein lipase in the kidneys of diet-induced diabetic minipigs

Liu

Wang

et al. 2011

Lipids Health Dis

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BackgroundThe role of renal lipoprotein lipase (LPL) per se in kidney diseases is still controversial and obscure. The purpose of this study was to observe the preventive effects of Ibrolipim, a LPL activator, on lipid accumulation and LPL expression in the kidneys of minipigs fed a high-sucrose and high-fat diet (HSFD).MethodsMale Chinese Bama minipigs were fed a control diet or HSFD with or without 0.1 g/kg/day Ibrolipim for 5 months. Body weight, plasma glucose, insulin, lipids, LPL activity, and urinary microalbumin were measured. Renal tissue was obtained for detecting LPL activity and contents of triglyceride and cholesterol, observing the renal lipid accumulation by Oil Red O staining, and examining the mRNA and protein expression of LPL by real time PCR, Western Blot and immunohistochemistry.ResultsFeeding HSFD to minipigs caused weight gain, hyperglycemia, hyperinsulinemia, hyperlipidemia and microalbuminuria. HSFD increased plasma LPL activity while it decreased the mRNA and protein expression and activity of LPL in the kidney. The increases in renal triglyceride and cholesterol contents were associated with the decrease in renal LPL activity of HSFD-fed minipigs. In contrast, supplementing Ibrolipim into HSFD lowered body weight, plasma glucose, insulin, triglyceride and urinary albumin concentrations while it increased plasma total cholesterol and HDL-C. Ibrolipim suppressed the renal accumulation of triglyceride and cholesterol, and stimulated the diet-induced down-regulation of LPL expression and activity in the kidney.ConclusionsIbrolipim exerts renoprotective and hypolipidemic effects via the increase in renal LPL activity and expression, and thus the increased expression and activity of renal LPL play a vital role in suppressing renal lipid accumulation and ameliorating proteinuria in diet-induced diabetic minipigs.

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Section: Discussionmentioning

confidence: 99%

Preventive effect of Ibrolipim on suppressing lipid accumulation and increasing lipoprotein lipase in the kidneys of diet-induced diabetic minipigs

Liu

Wang

et al. 2011

Lipids Health Dis

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“…The underlying methodology of pharmacophore model was defined by different researchers [33]. Recently, this model was successfully applied in mesangial cell proliferation inhibitor discovery and virtual screening of potential ligands for many targets such as HIV integrase and CCR5 antagonist [34][35][36][37]. In 3D pharmacophore model, the molecular spatial features and volume constraints represent the intrinsic interactions of small bioactive ligands with protein receptors.…”

Section: Ligand-based Approachmentioning

confidence: 99%

Exploring the Ligand-Protein Networks in Traditional Chinese Medicine: Current Databases, Methods and Applications

Zhao

Wei

2014

Advances in Experimental Medicine and Biology

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The traditional Chinese medicine (TCM), which has thousands of years of clinical application among China and other Asian countries, is the pioneer of the "multicomponent-multitarget" and network pharmacology. Although there is no doubt of the efficacy, it is difficult to elucidate convincing underlying mechanism of TCM due to its complex composition and unclear pharmacology. The use of ligand-protein networks has been gaining significant value in the history of drug discovery while its application in TCM is still in its early stage. This paper firstly surveys TCM databases for virtual screening that have been greatly expanded in size and data diversity in recent years. On that basis, different screening methods and strategies for identifying active ingredients and targets of TCM are outlined based on the amount of network information available, both on sides of ligand bioactivity and the protein structures. Furthermore, applications of successful in silico target identification attempts are discussed in detail along with experiments in exploring the ligand-protein networks of TCM. Finally, it will be concluded that the prospective application of ligand-protein networks can be used not only to predict protein targets of a small molecule, but also to explore the mode of action of TCM.

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“…HyPoGen was builded by three steps: Constructive phase, Subtractive phase, and Optimization phase [15], [16]. The confidence level of 95% was generated from 19 random spreadsheets by CatScramble program in each modeling run [11].…”

Section: B Pharmacophore Hypotheses Generation and Activity Predictionmentioning

confidence: 99%

“…For development potent inhibitors, 18 compounds from Lu's study were employed to build pharmacophore hypotheses [9], [10]. The predictive pharmacophores were generated by hypotheses generation (HypoGen) algorism, which could show common features of the 18 compounds and distances between each feature [11], [12]. The features and distances constructed pharmacophire map for database screening [13], [14].…”

Section: Introductionmentioning

confidence: 99%

Is that Possible to Design the Versatile Inhibitors for H1N1, H5N1, H5N2, and H5N7?

Chen

Bau

Tsai

et al. 2009

2009 2nd International Conference on Biomedical Engineering and Informatics

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In this study, a QSAR model of neuraminidase (NA) type 1 (N1) was elevated. This map contained two hydrogen bond acceptor features, one hydrogen bond donor features, and one positive ionizable feature. In the second step, we created the interaction maps in the active sites on the neuraminidase type2, and type7 (N2 and N7) protein structures. The structure-based pharmacophore map was showed the features on every amino acid in the active site on the protein structure. The third step was pharmacophore comparison, root-mean-squared error (RMSE) was reported for the matching pharmacophore features. The result showed that the maps of N1, N2, and N7 had subtle differences in distances of each features. We created the combined map for N1, N2, and N7 to resolving the difference in the three NA types. The combined map was employed to NCI database screening, then, the potent versatile inhibitors were elevated in the results.

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Discovery of Novel Mesangial Cell Proliferation Inhibitors Using a Three-Dimensional Database Searching Method

Cited by 34 publications

References 16 publications

Preventive effect of Ibrolipim on suppressing lipid accumulation and increasing lipoprotein lipase in the kidneys of diet-induced diabetic minipigs

Preventive effect of Ibrolipim on suppressing lipid accumulation and increasing lipoprotein lipase in the kidneys of diet-induced diabetic minipigs

Exploring the Ligand-Protein Networks in Traditional Chinese Medicine: Current Databases, Methods and Applications

Is that Possible to Design the Versatile Inhibitors for H1N1, H5N1, H5N2, and H5N7?

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