Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The medication use evaluation (MUE) Program at the University of Iowa Hospitals and Clinics (UIHC) is a dynamic program that is constantly changing to meet the needs of this tertiary care institution. This article will provide an overview of the MUE process at UIHC as well as provide an example of a long-standing initiative that has evolved significantly since its inception in 1993. Examples of four other initiatives also will be provided to demonstrate the scope of this program. The examples to be covered in this article include: 5-HT3 receptor antagonists, alteplase, automatic substitution of cefotaxime, proton pump inhibitors, and COX-2 selective agents.
 ...
PMID:Medication use evaluation: a work in progress. 1118 46

A primary goal of 3D similarity searching is to find compounds with similar bioactivity to a reference ligand but with different chemotypes, i.e., "scaffold hopping". However, an adequate description of chemical structures in 3D conformational space is difficult due to the high-dimensionality of the problem. We present an automated method that simplifies flexible 3D chemical descriptions in which clustering techniques traditionally used in data mining are exploited to create "fuzzy" molecular representations called FEPOPS (feature point pharmacophores). The representations can be used for flexible 3D similarity searching given one or more active compounds without a priori knowledge of bioactive conformations or pharmacophores. We demonstrate that similarity searching with FEPOPS significantly enriches for actives taken from in-house high-throughput screening datasets and from MDDR activity classes COX-2, 5-HT3A, and HIV-RT, while also scaffold or ring-system hopping to new chemical frameworks. Further, inhibitors of target proteins (dopamine 2 and retinoic acid receptor) are recalled by FEPOPS by scaffold hopping from their associated endogenous ligands (dopamine and retinoic acid). Importantly, the method excels in comparison to commonly used 2D similarity methods (DAYLIGHT, MACCS, Pipeline Pilot fingerprints) and a commercial 3D method (Pharmacophore Distance Triplets) at finding novel scaffold classes given a single query molecule.
 ...
PMID:A 3D similarity method for scaffold hopping from known drugs or natural ligands to new chemotypes. 1556 86

The use of a recently proposed hydrophobic similarity index for the alignment of molecules and the prediction of their differences in biological activity is described. The hydrophobic similarity index exploits atomic contributions to the octanol/water transfer free energy, which are evaluated by means of the fractional partitioning scheme developed within the framework of the Miertus-Scrocco-Tomasi continuum model. Those contributions are used to define global and local measures of hydrophobic similarity. The suitability of this computational strategy is examined for two series of compounds (ACAT inhibitors and 5-HT3 receptor agonists), which are aligned to maximize the global hydrophobic similarity using a Monte Carlo-simulated protocol. Indeed, the concept of local hydrophobic similarity is used to explore structure-activity relationships in a series of COX-2 inhibitors. Inspection of the 3D distribution of hydrophobic/hydrophilic contributions in the aligned molecules is valuable to identify regions of very similar hydrophobicity, which can define pharmacophoric recognition patterns. Moreover, low similar regions permit to identify structural elements that modulate the differences in activity between molecules. Finally, the quantitative relationships found between the pharmacological activity and the hydrophobic similarity index points out that not only the global hydrophobicity, but its 3D distribution, is important to gain insight into the activity of molecules.
 ...
PMID:Hydrophobic molecular similarity from MST fractional contributions to the octanol/water partition coefficient. 1623 Dec

Cuscuta reflexa Roxb. is traditionally used by the indigenous communities of Bangladesh to treat different diseases, such as pain, edema, tumor, jaundice, and skin infections. This study tested neuro-pharmacological, anti-nociceptive, and antidiarrheal activities by in vivo and in silico experiments for the metabolites extracted (methanol) from the leaves of Cuscuta reflexa (MECR). During the anxiolytic evaluation analyzed by elevated plus maze and hole board tests, MECR (200 and 400 mg/kg) exhibited a significant dose-dependent reduction of anxiety-like behavior in mice. Similarly, mice treated with MECR demonstrated a dose-dependent decrease in the time of immobility in both forced swimming and tail suspension tests. In addition, anti-nociceptive activity was assessed by the chemical-induced (acetic acid and formalin) pain models. In both cases, 400 mg/kg was found to be most effective and significantly (p < 0.001) inhibited acetic acid stimulated writhing and formalin-induced licking (pain response) in mice. Furthermore, antidiarrheal efficacy determined by the castor-oil induced diarrheal model manifested an evident inhibition of diarrheal stool frequency. In parallel, previously isolated bioactive compounds were documented based on the biological activities and subjected to in silico studies to correlate with the current pharmacological outcomes. The selected isolated compounds (15) displayed favorable binding affinities to potassium channels, human serotonin receptor, COX-1, COX-2, M3 muscarinic acetylcholine receptor, and 5-HT3 receptor proteins. Additionally, the ADME/T and toxicological properties were justified to unveil their drug-like properties and toxicity level. Overall, Cuscuta reflexa is bioactive and could be a potential source for the development of alternative medicine.
 ...
PMID:Unveiling Pharmacological Responses and Potential Targets Insights of Identified Bioactive Constituents of Cuscuta reflexa Roxb. Leaves through In Vivo and In Silico Approaches. 3224 31