Substitution pattern reverses the fluorescence response of coumarin glycoligands upon coordination with silver (I).

Development of sugar-based fluorescence (FL) chemo-probes is of much interest since sugars are biocompatible, water-soluble and structurally rigid natural starting materials. We report here that fluorescent glycoligands with two triazolyl coumarin moieties installed onto the different positions of an identical glucosyl nucleus exert completely reversed optical response to a metal ion. C3,4-, C2,3- and C4,6-di-substituted coumarin glucosides synthesized by a click reaction similarly showed a selective FL variation in the presence of silver (I) among a range of metal cations in an aqueous solution.

Structure-based ensemble-QSAR model: a novel approach to the study of the EGFR tyrosine kinase and its inhibitors.

Aim: To develop a novel 3D-QSAR approach for study of the epidermal growth factor receptor tyrosine kinase (EGFR TK) and its inhibitors.

Methods: One hundred thirty nine EGFR TK inhibitors were classified into 3 clusters. Ensemble docking of these inhibitors with 19 EGFR TK crystal structures was performed.

[Development of full-quantified HPLC fingerprint for quality evaluation of ophiopogonis radix of sichuan].

Objective: To establish HPLC fingerprint of Ophiopogonis Radix of Sichuan and simultaneously determine two homoisoflavonoids (methylophiopogonanones A and B).

Methods: Full-quantified HPLC fingerprint was used to establish the HPLC fingerprint and determine the active ingredients of the daodi medicinal material Ophiopogonis Radix of Sichuan in Shengmai injection. Chromatographic condition was as follows: The analytical column was Waters symmetry shield RP 18 (4.

Prognostic significance of KAI1/CD82 in human melanoma and its role in cell migration and invasion through the regulation of ING4.

KAI1/CD82 is a member of the transmembrane 4 superfamily, which was first identified as a metastasis suppressor for prostate cancer. The expression of KAI1 was found to be reduced in many types of cancers, including prostate, breast, ovarian, cervical and endometrial cancer. However, the role of KAI1 in melanoma pathogenesis is not known.

JWA inhibits melanoma angiogenesis by suppressing ILK signaling and is an independent prognostic biomarker for melanoma.

Melanoma is the deadliest cutaneous malignancy because of its high incidence of metastasis. Melanoma growth and metastasis relies on sustained angiogenesis; therefore, inhibiting angiogenesis is a promising approach to treat metastatic melanoma. JWA is a novel microtubule-associated protein and our previous work revealed that JWA inhibited melanoma cell invasion and metastasis.

[Simultaneous determination of five flavonoids and specific chromatograms analysis of huangkui capsule].

Objective: To Set up a method for determining the contents of the five flavonoids simultaneously in the HuangKui capsule and analyze their specific chromatograms.

Methods: HPLC method was used. The analytical column was Thermo scientific Hypersil GOLD (250 mm x 4.

In silico ADMET prediction: recent advances, current challenges and future trends.

There are numerous small molecular compounds around us to affect our health, such as drugs, pesticides, food additives, industrial chemicals, and environmental pollutants. Over decades, properties related to absorption, distribution, metabolism, excretion, and toxicity (ADMET) have become one of the most important issues to assess the effects or risks of these compounds on human body. Recent high-rate drug withdrawals increase the pressure on regulators and pharmaceutical industry to improve preclinical safety testing.

Computational insights into the binding modes of Sr-Rex with cofactor NADH/NAD+ and operator DNA.

The transcriptional repressor Rex plays key roles in modulating respiratory gene expression. It senses the redox poise of the NAD(H) pool. Rex from Streptomyces rimosus (Sr-Rex) is a newly identified protein.

Prediction of polypharmacological profiles of drugs by the integration of chemical, side effect, and therapeutic space.

Prediction of polypharmacological profiles of drugs enables us to investigate drug side effects and further find their new indications, i.e. drug repositioning, which could reduce the costs while increase the productivity of drug discovery.

Adverse drug events: database construction and in silico prediction.

Adverse drug events (ADEs) are the harms associated with uses of given medications at normal dosages, which are crucial for a drug to be approved in clinical use or continue to stay on the market. Many ADEs are not identified in trials until the drug is approved for clinical use, which results in adverse morbidity and mortality. To date, millions of ADEs have been reported around the world.

Prediction of human genes and diseases targeted by xenobiotics using predictive toxicogenomic-derived models (PTDMs).

New technologies for systems-level determinants of human exposure to drugs, industrial chemicals, pesticides, and other environmental agents provide an invaluable opportunity to extend the understanding of human health and potential environmental hazards. We report here the development of a new computational-systems toxicology framework, called predictive toxicogenomics-derived models (PTDMs). PTDMs integrate three networks of chemical-gene interactions (CGIs), chemical-disease associations (CDAs) and gene-disease associations (GDAs) to infer chemical hazard profiles, identify exposure data gaps and to incorporate genes and disease networks into chemical safety evaluations.

The oncogenic role of microRNA-130a/301a/454 in human colorectal cancer via targeting Smad4 expression.

Transforming growth factor (TGF)-β/Smad signaling plays an important role in colon cancer development, progression and metastasis. In this study we demonstrated that the microRNA-130a/301a/454 family is up-regulated in colon cancer tissues compared to paired adjacent normal mucosa, which share the same 3'-untranslational region (3'-UTR) binding seed sequence and are predicated to target Smad4. In colorectal cancer HCT116 and SW480 cells, overexpression of miRNA-130a/301a/454 mimics enhances cell proliferation and migration, while inhibitors of these miRNAs affect cell survival.

What should be the data sharing policy of cognitive science?

There is a growing chorus of voices in the scientific community calling for greater openness in the sharing of raw data that lead to a publication. In this commentary, we discuss the merits of sharing, common concerns that are raised, and practical issues that arise in developing a sharing policy. We suggest that the cognitive science community discuss the topic and establish a data-sharing policy.

Pharmacophore, 3D-QSAR, and Bayesian model analysis for ligands binding at the benzodiazepine site of GABAA receptors: the key roles of amino group and hydrophobic sites.

Ligands binding at the benzodiazepine site of GABAA receptor play important pharmacological roles in clinical application. In this study, ligand-based pharmacophore modeling, 3D-QSAR analysis, and Bayesian model studies have been performed on a set of 84 diverse ligands binding at the benzodiazepine site. The results showed the best pharmacophore hypothesis AADHR.

Design, synthesis and biological evaluation of organophosphorous-homodimers as dual binding site acetylcholinesterase inhibitors.

The cluster effect is an effective strategy to explore new lead compounds, and has been successfully applied in rational drug design and screening. A series of novel organophosphorous-homodimers were designed and synthesized based on the dual-site structure characteristics of acetylcholinesterase (AChE). The compounds were evaluated in vitro for their inhibitory activity to AChE extracted from Drosophila melanogaster and Musca domestic.

Unbinding pathways of GW4064 from human farnesoid X receptor as revealed by molecular dynamics simulations.

Farnesoid X receptor (FXR, NR1H4) is a member of a nuclear receptor superfamily, which plays important roles in bile acid homeostasis, lipoprotein and glucose metabolism, and hepatic regeneration. GW4064 is a potent and selective FXR agonist and has become a tool compound to probe the physiological functions of FXR. Until now, the mechanism of GW4064 entering and leaving the FXR pocket is still poorly understood.

admetSAR: a comprehensive source and free tool for assessment of chemical ADMET properties.

Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties play key roles in the discovery/development of drugs, pesticides, food additives, consumer products, and industrial chemicals. This information is especially useful when to conduct environmental and human hazard assessment. The most critical rate limiting step in the chemical safety assessment workflow is the availability of high quality data.

Discovery of inhibitors to block interactions of HIV-1 integrase with human LEDGF/p75 via structure-based virtual screening and bioassays.

This study aims to identify inhibitors that bind at the interface of HIV-1 integrase (IN) and human LEDGF/p75, which represents a novel target for anti-HIV therapy. To date, only a few such inhibitors have been reported. Here structure-based virtual screening was performed to search for the inhibitors from an in-house library of natural products and their derivatives.

Discovery of new non-steroidal FXR ligands via a virtual screening workflow based on Phase shape and induced fit docking.

Farnesol X receptor (FXR) is a member of the metabolic nuclear receptor (NR) superfamily of regulatory proteins. FXR was recognized to be a transcriptional sensor for bile acids, and now it has been shown that activating FXR has important roles in controlling bile acid homeostasis, lipoprotein and glucose metabolism, and hepatic regeneration. For the sake of discovering new, potent non-steroidal FXR ligands, we have established a virtual screening workflow by using Phase Shape and induced fit docking (IFD).

In silico prediction of chemical Ames mutagenicity.

Mutagenicity is one of the most important end points of toxicity. Due to high cost and laboriousness in experimental tests, it is necessary to develop robust in silico methods to predict chemical mutagenicity. In this paper, a comprehensive database containing 7617 diverse compounds, including 4252 mutagens and 3365 nonmutagens, was constructed.

[Progress in the ligands and their complex structures of farnesoid X receptor].

Farnesoid X receptor (FXR) belongs to the nuclear receptor superfamily. It is highly related to the formation of metabolic syndrome and the glucose homeostasis, and therefore represents an important drug target against metabolic diseases and diabetes. In recent years, great progress has been made in the agonists, antagonists, and crystal structures of FXR.

Prediction of chemical-protein interactions network with weighted network-based inference method.

Chemical-protein interaction (CPI) is the central topic of target identification and drug discovery. However, large scale determination of CPI is a big challenge for in vitro or in vivo experiments, while in silico prediction shows great advantages due to low cost and high accuracy. On the basis of our previous drug-target interaction prediction via network-based inference (NBI) method, we further developed node- and edge-weighted NBI methods for CPI prediction here.

Long-lived charge-separated states in ligand-stabilized silver clusters.

Recently developed synthesis methods allow for the production of atomically monodisperse clusters of silver atoms stabilized in solution by aromatic thiol ligands, which exhibit intense absorption peaks throughout the visible and near-IR spectral regions. Here we investigated the time-dependent optical properties of these clusters. We observed two kinetic processes following ultrafast laser excitation of any of the absorption peaks: a rapid decay, with a time constant of 1 ps or less, and a slow decay, with a time constant that can be longer than 300 ns.

Prediction of chemical-protein interactions: multitarget-QSAR versus computational chemogenomic methods.

Elucidation of chemical-protein interactions (CPI) is the basis of target identification and drug discovery. It is time-consuming and costly to determine CPI experimentally, and computational methods will facilitate the determination of CPI. In this study, two methods, multitarget quantitative structure-activity relationship (mt-QSAR) and computational chemogenomics, were developed for CPI prediction.

Identification of old drugs as potential inhibitors of HIV-1 integrase - human LEDGF/p75 interaction via molecular docking.

Integration of viral-DNA into host chromosome mediated by the viral protein HIV-1 integrase (IN) is an essential step in the HIV-1 life cycle. In this process, human protein Lens epithelium-derived growth factor (LEDGF/p75) is discovered to function as a cellular co-factor for integration. LEDGF/p75-HIV-1 IN interaction represents an attractive target for anti-HIV therapy.