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Protein Tyrosine Phosphatase Inhibitors (protein tyrosine + phosphatase_inhibitor)
Selected AbstractsThe Core Structures of Roseophilin and the Prodigiosin Alkaloids Define a New Class of Protein Tyrosine Phosphatase InhibitorsCHEMBIOCHEM, Issue 11 2004Alois Fürstner Prof. A common core. Protein phosphatases, such as the dual-specificity phosphatase VHR and the tyrosine phosphatase PTP1B, are key regulators of innumerable cellular processes, and new classes of phosphatase inhibitors are in demand. The azafulvene-containing core structures of the roseophilin and prodigiosin alkaloids define such a new class. [source] Biaryls and Heterobiaryls as ,-Glucosidase and Protein Tyrosine Phosphatase Inhibitors.CHEMINFORM, Issue 28 2005Ashoke Sharon Abstract For Abstract see ChemInform Abstract in Full Text. [source] Stimulatory effects of the soy phytoestrogen genistein on noradrenaline transporter and serotonin transporter activityMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 4 2010Yumiko Toyohira Abstract We examined the effects of genistein, one of the major soy phytoestrogens, on the activity of noradrenaline transporter (NAT) and serotonin transporter. Treatment with genistein (10,nM,10,,M) for 20,min stimulated [3H]noradrenaline (NA) uptake by SK-N-SH cells. Genistein also stimulated [3H]NA uptake and [3H]serotonin uptake by NAT and serotonin transporter transiently transfected COS-7 cells, respectively. Kinetics analysis of the effect of genistein on NAT activity in NAT-transfected COS-7 cells revealed that genistein significantly increased the maximal velocity of NA transport with little or no change in the affinity. Scatchard analysis of [3H]nisoxetine binding to NAT-transfected COS-7 cells showed that genistein increased the maximal binding without altering the dissociation constant. Although genistein is also known to be an inhibitor of tyrosine kinases, daidzein, another soy phytoestrogen and an inactive genistein analogue against tyrosine kinases, had little effect on [3H]NA uptake by SK-N-SH cells. The stimulatory effects on NAT activity were observed by treatment of tyrphostin 25, an inhibitor of epidermal growth factor receptor tyrosine kinase, whereas orthovanadate, a protein tyrosine phosphatase inhibitor, suppressed [3H]NA uptake by NAT-transfected COS-7 cells. These findings suggest that genistein up-regulates the activity of neuronal monoamine transporters probably through processes involving protein tyrosine phosphorylation. [source] Therapeutic potential of sulfamides as enzyme inhibitorsMEDICINAL RESEARCH REVIEWS, Issue 6 2006Jean-Yves Winum Abstract Sulfamide, a quite simple molecule incorporating the sulfonamide functionality, widely used by medicinal chemists for the design of a host of biologically active derivatives with pharmacological applications, may give rise to at least five types of derivatives, by substituting one to four hydrogen atoms present in it, which show specific biological activities. Recently, some of these compounds started to be exploited for the design of many types of therapeutic agents. Among the enzymes for which sulfamide-based inhibitors were designed, are the carbonic anhydrases (CAs), a large number of proteases belonging to the aspartic protease (HIV-1 protease, ,-secretase), serine protease (elastase, chymase, tryptase, and thrombin among others), and metalloprotease (carboxypeptidase A (CPA) and matrix metalloproteinases (MMP)) families. Some steroid sulfatase (STS) and protein tyrosine phosphatase inhibitors belonging to the sulfamide class of derivatives have also been reported. In all these compounds, many of which show low nanomolar affinity for the target enzymes for which they have been designed, the free or substituted sulfamide moiety plays important roles for the binding of the inhibitor to the active site cavity, either by directly coordinating to a metal ion found in some metalloenzymes (CAs, CPA, STS), usually by means of one of the nitrogen atoms present in the sulfamide motif, or as in the case of the cyclic sulfamides acting as HIV protease inhibitors, interacting with the catalytically critical aspartic acid residues of the active site by means of an oxygen atom belonging to the HNSO2NH motif, which substitutes a catalytically essential water molecule. In other cases, the sulfamide moiety is important for inducing desired physico-chemical properties to the drug-like compounds incorporating it, such as enhanced water solubility, better bioavailability, etc., because of the intrinsic properties of this highly polarized moiety when attached to an organic scaffold. This interesting motif is thus of great value for the design of pharmacological agents with a lot of applications. © 2006 Wiley Periodicals, Inc. Med Res Rev [source] | ||||||||||