Epigenomic Networking in Drug Development: From Pathogenic Mechanisms to Pharmacogenomics
Abstract
Different epigenetic alterations (DNA methylation, histone modifications, chromatin remodeling, noncoding RNA dysregulation) are associated with the phenotypic expression of complex disorders in which genomic, epigenomic, proteomic, and metabolomic changes, in conjunction with environmental factors, are involved. As epigenetic modifications are reversible and can be potentially targeted by pharmacological and dietary interventions, a series of epigenetic drugs have been developed, including DNA methyltransferase inhibitors (nucleoside analogs, small molecules, bioproducts, antisense oligonucleotides, miRNAs...
Source: Drug Development Research - September 4, 2014 Category: Drugs & Pharmacology Authors: Ramón Cacabelos Tags: Research Overview Source Type: research
Correcting Transcription Factor Gene Sets for Copy Number and Promoter Methylation Variations
Abstract
Gene set analysis provides a method to generate statistical inferences across sets of linked genes, primarily using high‐throughput expression data. Common gene sets include biological pathways, operons, and targets of transcriptional regulators. In higher eukaryotes, especially when dealing with diseases with strong genetic and epigenetic components such as cancer, copy number loss and gene silencing through promoter methylation can eliminate the possibility that a gene is transcribed. This, in turn, can adversely affect the estimation of transcription factor or pathway activity from a set of target gene...
Source: Drug Development Research - September 4, 2014 Category: Drugs & Pharmacology Authors: Komal S. Rathi, Daria A. Gaykalova, Patrick Hennessey, Joseph A. Califano, Michael F. Ochs Tags: Research Article Source Type: research
Coadministration of Tramadol and Tizanidine in an Experimental Acute Pain Model in Rat
Abstract
The use of drug combinations to achieve a desired effect is a common practice in pharmacological reaserch and in clinical practice. The present study was designed to evaluate the potential synergistic antinociceptive interactions between tizanidine, an α‐2‐adrenoceptor agonist and tramadol on formalin‐induced nociception in rat using isobolographic analyses. Tramadol (0.1–100 μg/paw) and tizanidine (0.01–10 μg/paw) were injected into the paw prior to formalin injection (1%). Both drugs produced a dose‐dependent antinociceptive effect. The EC50 values were estimated for individual drugs, a...
Source: Drug Development Research - September 1, 2014 Category: Drugs & Pharmacology Authors: Karla Lizet Beltrán‐Villalobos, Pamela Monserrat Ramírez‐Marín, Carlos Alberto Zúñiga Cruz, Myrna Déciga‐Campos Tags: Research Article Source Type: research
Visualization of Plasma and Tissue Binding Using Dose Fractions Parameter
Abstract
A novel concept of dose fractions, based on the distribution of total bioavailable dose between the six combinations of location and binding state in Øie–Tozer's model is suggested as a way to visualize the distribution pharmacokinetics of a drug. The concept of dose fractions provides a sharper terminology in discussions of drug distribution allowing for a more precise description of the state and location of a drug within a system. In medicinal chemistry literature, the free fraction of a drug in plasma is a commonly discussed factor affecting the exposure to free drug while tissue binding is less well addres...
Source: Drug Development Research - September 1, 2014 Category: Drugs & Pharmacology Authors: Andreas Svennebring Tags: Research Article Source Type: research
The Organic Chemistry of Drug Design and Drug Action 3rd ed. by Richard B. Silverman and Mark W. Holladay, San Diego,CA: Academic Press, 2014, ISBN—print 978‐0‐12–382030‐3, e‐book 978‐0‐12–382031‐0; xviii + 517 pp. Print $99.95, e‐book $99.95.
(Source: Drug Development Research)
Source: Drug Development Research - September 1, 2014 Category: Drugs & Pharmacology Authors: Michael Williams Tags: Book Review Source Type: research
