Glycyrrhetinic Acid Exhibits Strong Inhibitory Effects Towards UDP-Glucuronosyltransferase (UGT) 1A3 and 2B7.
Glycyrrhetinic Acid Exhibits Strong Inhibitory Effects Towards UDP-Glucuronosyltransferase (UGT) 1A3 and 2B7.
Filed under: Drug and Alcohol Rehabilitation
Phytother Res. 2012 Nov 12;
Huang YP, Cao YF, Fang ZZ, Zhang YY, Hu CM, Sun XY, Yu ZW, Zhu X, Hong M, Yang L, Sun HZ
The aim of the present study is to evaluate the inhibitory effects of liver UDP-glucuronosyltransferases (UGTs) by glycyrrhizic acid and glycyrrhetinic acid, which are the bioactive ingredients isolated from licorice. The results showed that glycyrrhetinic acid exhibited stronger inhibition towards all the tested UGT isoforms, indicating that the deglycosylation process played an important role in the inhibitory potential towards UGT isoforms. Furthermore, the inhibition kinetic type and parameters were determined for the inhibition of glycyrrhetinic acid towards UGT1A3 and UGT2B7. Data fitting using Dixon and Lineweaver-Burk plots demonstrated that the inhibition of UGT1A3 and UGT2B7 by glycyrrhetinic acid was best fit to competitive and noncompetitive type, respectively. The second plot using the slopes from Lineweaver-Burk plots versus glycyrrhetinic acid concentrations was employed to calculate the inhibition kinetic parameters (K(i) ), and the values were calculated to be 0.2 and 1.7??M for UGT1A3 and UGT2B7, respectively. All these results remind us the possibility of UGT inhibition-based herb-drug interaction. However, the explanation of these in vitro parameters should be paid more caution due to complicated factors, including the probe substrate-dependent UGT inhibition behaviour, environmental factors affecting the abundance of herbs’ ingredients, and individual difference of pharmacokinetic factors. Copyright © 2012 John Wiley & Sons, Ltd.
HubMed – drug
Disease modelling using induced pluripotent stem cells: Status and prospects.
Filed under: Drug and Alcohol Rehabilitation
Bioessays. 2012 Nov 13;
Pomp O, Colman A
The ability to convert human somatic cells into induced pluripotent stem cells (iPSCs) is allowing the production of custom-tailored cells for drug discovery and for the study of disease phenotypes at the cellular and molecular level. IPSCs have been derived from patients suffering from a large variety of disorders with different severities. In many cases, disease related phenotypes have been observed in iPSCs or their lineage-specific progeny. Several proof of concept studies have demonstrated that these phenotypes can be reversed in vitro using approved drugs. However, several challenges must be overcome to take full advantage of this technology. Here, we highlight recent advances in the field and discuss the main challenges associated with this technology as it applies to disease modelling.
HubMed – drug
High-throughput identification of putative receptors for cancer-binding peptides using biopanning and microarray analysis.
Filed under: Drug and Alcohol Rehabilitation
Integr Biol (Camb). 2012 Nov 13;
Ferraro DJ, Bhave SR, Kotipatruni RP, Hunn JC, Wildman SA, Hong C, Dadey DY, Muhoro LK, Jaboin JJ, Thotala D, Hallahan DE
Phage-display peptide biopanning has been successfully used to identify cancer-targeting peptides in multiple models. For cancer-binding peptides, identification of the peptide receptor is necessary to demonstrate the mechanism of action and to further optimize specificity and target binding. The process of receptor identification can be slow and some peptides may turn out to bind ubiquitous proteins not suitable for further drug development. In this report, we describe a high-throughput method for screening a large number of peptides in parallel to identify peptide receptors, which we have termed “reverse biopanning.” Peptides can then be selected for further development based on their receptor. To demonstrate this method, we screened a library of 39 peptides previously identified in our laboratory to bind specifically to cancers after irradiation. The reverse biopanning process identified 2 peptides, RKFLMTTRYSRV and KTAKKNVFFCSV, as candidate ligands for the protein tax interacting protein 1 (TIP-1), a protein previously identified in our laboratory to be expressed in tumors and upregulated after exposure to ionizing radiation. We used computational modeling as the initial method for rapid validation of peptide-TIP-1 binding. Pseudo-binding energies were calculated to be -360.645 kcal mol(-1), -487.239 kcal mol(-1), and -595.328 kcal mol(-1) for HVGGSSV, TTRYSRV, and NVFFCSV respectively, suggesting that the peptides would have at least similar, if not stronger, binding to TIP-1 compared to the known TIP-1 binding peptide HVGGSSV. We validated peptide binding in vitro using electrophoretic mobility shift assay, which showed strong binding of RKFLMTTRYSRV and the truncated form TTRYSRV. This method allows for the identification of many peptide receptors and subsequent selection of peptides for further drug development based on the peptide receptor.
HubMed – drug
Nebulized arformoterol: what is its place in the management of COPD?
Filed under: Drug and Alcohol Rehabilitation
Ther Adv Respir Dis. 2012 Nov 12;
Miles MC, Donohue JF, Ohar JA
Chronic obstructive pulmonary disease (COPD) is a serious global health burden. Comprehensive management of COPD includes both pharmacologic and non-pharmacologic interventions aimed at improving disease-related functional capacity, health-related quality of life, and survival. The primary medications used for treatment of COPD are inhaled bronchodilator drugs which are delivered directly to the patient’s airways through a number of different mechanisms. Arformoterol, the (R,R) enantiomer of racemic formoterol, was the first long-acting beta agonist approved by the U.S. Food and Drug Administration (FDA) for nebulized delivery. We discuss the pharmacology, clinical efficacy, and safety of arformoterol, and provide recommendations for its use during longitudinal management of patients with COPD.
HubMed – drug
Kidney cancer: CRM1-a novel drug target for renal cell carcinoma?
Filed under: Drug and Alcohol Rehabilitation
Nat Rev Urol. 2012 Nov 13;
Payton S
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