Investigation of the Novel Lead of Melanocortin 1 Receptor for Pigmentary Disorders

Tang, Hsin-Chieh; Chen, Calvin Yu-Chian

doi:10.1155/2014/254678

Cited by 11 publications

(7 citation statements)

References 81 publications

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“…The bioactivity of 61,000 compounds extracted from TCM herbs can be searched through the database portal. The TCM Database@Taiwan application has been investigated for treatments of insomnia, 29 pigmentary disorders, 30 and Parkinson’s disease, 31 as well as epidermal growth factor receptor (EGFR) inhibition, 32 pain relief, 33 and viral infections. 34 – 38 It is helpful to screen TCM compounds via a cloud computing platform.…”

Section: Methodsmentioning

confidence: 99%

Simultaneous targeting of MyD88 and Nur77 as an effective approach for the treatment of inflammatory diseases

Saqib

Baig²

2016

DDDT

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Myeloid differentiation primary response protein 88 (MyD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MyD88 and Nur77 at the same time. Since both MyD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MyD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MyD88 and Nur77 targets.

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Section: Methodsmentioning

confidence: 99%

Simultaneous targeting of MyD88 and Nur77 as an effective approach for the treatment of inflammatory diseases

Saqib

Baig²

2016

DDDT

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“…This database contains 2D chemical structures, 3D chemical structures, bioactivity, and molecular information of 61,000 compounds used in Traditional Chinese Medicine. Since 2011, there have been successful discoveries in novel lead compounds from the TCM Database@Taiwan [ 33 – 35 ], including compounds for the putative treatment of AD [ 36 ], Parkinson's Disease [ 37 ], insomnia [ 38 ], pigmentary disorders [ 39 ], and even antivirals [ 40 – 44 ]. Due to the application system of the website [ 45 ] and cloud computing platforms [ 46 ], the TCM Database@Taiwan is exceptionally helpful for TCM applications and drug design.…”

Section: Introductionmentioning

confidence: 99%

In SilicoInvestigation of Traditional Chinese Medicine Compounds to Inhibit Human Histone Deacetylase 2 for Patients with Alzheimer’s Disease

Hung

Chen

Chan

et al. 2014

BioMed Research International

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Human histone deacetylase 2 (HDAC2) has been identified as being associated with Alzheimer's disease (AD), a neuropathic degenerative disease. In this study, we screen the world's largest Traditional Chinese Medicine (TCM) database for natural compounds that may be useful as lead compounds in the search for inhibitors of HDAC2 function. The technique of molecular docking was employed to select the ten top TCM candidates. We used three prediction models, multiple linear regression (MLR), support vector machine (SVM), and the Bayes network toolbox (BNT), to predict the bioactivity of the TCM candidates. Molecular dynamics simulation provides the protein-ligand interactions of compounds. The bioactivity predictions of pIC50 values suggest that the TCM candidatesm, (−)-Bontl ferulate, monomethylcurcumin, and ningposides C, have a greater effect on HDAC2 inhibition. The structure variation caused by the hydrogen bonds and hydrophobic interactions between protein-ligand interactions indicates that these compounds have an inhibitory effect on the protein.

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“…The TCM Database@Taiwan ( http://tcm.cmu.edu.tw/ ) is the world's largest TCM database [ 13 ]. In this database the molecular structure and bioactivity of 61,000 TCM compounds are available for screening and many applications of TCM have been identified, such as insomnia treatment [ 14 ], pigmentary disorders treatment [ 15 ], Parkinson's disease prevention [ 16 ], EGFR inhibition [ 17 ], inflammation inhibition [ 18 ], pain relief [ 5 ], and antivirals [ 19 – 23 ]. Today, the screening of TCM compounds from the database is possible by cloud-computing web server [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

The Inhibition of Folylpolyglutamate Synthetase (folC) in the Prevention of Drug Resistance inMycobacterium tuberculosisby Traditional Chinese Medicine

Hung

Chen

2014

BioMed Research International

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Tuberculosis (TB) is an infectious disease caused by many strains of mycobacteria, but commonly Mycobacterium tuberculosis. As a possible method of reducing the drug resistance of M. tuberculosis, this research investigates the inhibition of Folylpolyglutamate synthetase, a protein transcript from the resistance association gene folC. After molecular docking to screen the traditional Chinese medicine (TCM) database, the candidate TCM compounds, with Folylpolyglutamate synthetase, were selected by molecular dynamics. The 10,000 ps simulation in association with RMSD analysis and total energy and structural variation defined the protein-ligand interaction. The selected TCM compounds Saussureamine C, methyl 3-O-feruloylquinate, and Labiatic acid have been found to inhibit the activity of bacteria and viruses and to regulate immunity. We also suggest the possible pathway in protein for each ligand. Compared with the control, similar interactions and structural variations indicate that these compounds might have an effect on Folylpolyglutamate synthetase. Finally, we suggest Saussureamine C is the best candidate compound as the complex has a high score, maintains its structural composition, and has a larger variation value than the control, thus inhibiting the drug resistance ability of Mycobacterium tuberculosis.

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Investigation of the Novel Lead of Melanocortin 1 Receptor for Pigmentary Disorders

Cited by 11 publications

References 81 publications

Simultaneous targeting of MyD88 and Nur77 as an effective approach for the treatment of inflammatory diseases

Simultaneous targeting of MyD88 and Nur77 as an effective approach for the treatment of inflammatory diseases

In SilicoInvestigation of Traditional Chinese Medicine Compounds to Inhibit Human Histone Deacetylase 2 for Patients with Alzheimer’s Disease

The Inhibition of Folylpolyglutamate Synthetase (folC) in the Prevention of Drug Resistance inMycobacterium tuberculosisby Traditional Chinese Medicine

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