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2009 NOV 23 ... factors, that have not been addressable with current small molecule or biologic drug modalities. There are estimated to be more than 1,500 transcription factors in the human ... T-cell acute lymphoblastic leukemia (T-ALL), that Stapled Peptides achieved tight direct binding to the Notch transcription factor complex, preventing the assembly of a functional ... in Nature in October 2008 titled "BAX Activation is Initiated at a Novel Interaction Site," Aileron Therapeutics collaborators at the Dana Farber Cancer Institute demonstrated ...
2009 NOV 23 ... ChemGenex Pharmaceuticals Limited (ASX:CXS) announced that the U.S. Food & Drug Administration (FDA) has accepted the company's New Drug Application (NDA) for ... of hematological malignancies. Omacetaxine has a novel mechanism of action, specifically binding to the ribosomal A-site cleft and inhibiting protein translation of short-lived ...
2009 NOV 23 ... NMDA receptor under the generic name Memantine has been approved by the U.S. Food and Drug Administration for use in moderate and severe cases of Alzheimer's. Memantine is a ... The team obtained structures of the ATD domain with and without zinc binding to it. Zinc is a natural ligand that docks at a spot within the "clamshell" in routine ... receptor. Of much greater interest is the location and nature of a suspected binding site of a small molecule type that is known to bind the ATD and inhibit the action of the ...
2009 NOV 23 ... Disease, Amyloidosis, Biochemistry, Biological Chemistry, Cloning, Diagnostics, Drug Development, Flu, Influenza, Nephrology, Pharmaceuticals, Therapy, Treatment. ... such as primary systemic amyloidosis. Additional experiments showed that amyloid binding activity is an intrinsic feature of a wide variety of isolated clonal (single) and ... of the next generation of scientists and physicians. For more information visit our web site at www.limr.org. Contact: Tava Shanchuk ...
2009 NOV 17 ... Johns Hopkins University, Medical Department. This article was prepared by Drug Law Weekly editors from staff and other reports. Copyright 2009, Drug Law Weekly via ... block. Moreover, F1236C and Q399C significantly decreased the affinity of QX-314 for binding to its channel receptor by 8.5- and 3.3-fold, respectively. Oddly enough, F1236C ... (SS1) of the S5-S6 linkers in channel gating and local anesthetic (LA) block using site-directed cysteine mutagenesis of the rat skeletal muscle (Na(V)1.4) channel." ...
2009 NOV 16 ... of Biological Chemistry, "Malaria remains a major global health burden and current drug therapies are compromised by resistance. Plasmodium falciparum dihydroorotate ... inhibitors. We demonstrate that conformational flexibility results in an unexpected binding mode identifying a new hydrophobic pocket on the enzyme. Importantly this plasticity ... with the enzyme. The importance of delocalization to binding affinity was supported by site-directed mutagenesis and the demonstration that triazolopyrimidine analogs that lack ...
2009 NOV 16 ... regulation by oxysterols." Cook and colleagues published their study in Drug Metabolism and Disposition (24-Hydroxycholesterol Sulfation by Human Cytosolic ... that 24-OHChol-24-sulfate binds in an active configuration in the SULT2A1 substrate bindingsite with high affinity only when the SULT2A1 homodimer structure was used. 24-OHChol is ...
2009 NOV 16 ... approved for the treatment of non-small-cell lung cancer by the State Food and Drug Administration in China, is a derivative of human endostatin that is modified with an ... (MGGSHHHHH) at the N-terminus. This modification contributes to an additional zinc-bindingsite in the endostatin sequence." "In the present study, zinc-binding and ...
2009 NOV 17 ... Molecular Therapies, Molecular Medicine. This article was prepared by Drug Law Weekly editors from staff and other reports. Copyright 2009, Drug Law Weekly via ... negative cooperativity (Hill coefficient = 0.49) and half-of-sites saturation binding stoichiometry (half-reaction order) for the binding of lidocaine to hTREK1. Studies with ... couplet (Tyr352 and Phe355) in the vicinity of the protein kinase A phosphorylation site, Ser348, in the C-terminal domain (CTD) of hTREK1, that is critical for the action of ...
2009 NOV 16 ... is often used as a model system to explain mechanisms of inhibition of DNA synthesis and drug resistance." "However, here we demonstrate that gp43 is similar to ... major determinants for drug activity, we replaced critical regions of the nucleotide-bindingsite of gp43 with equivalent regions of the HCMV enzyme. We show that chimeric gp43-UL54 ...
2009 NOV 16 ... acids caused resistance to T1249, and none caused resistance to T2635. Depending on the drug, we can distinguish four mechanisms of drug resistance: reduced contact, steric ... in Netherlands report. "Resistance to T20 usually maps to the peptide bindingsite in HR1. To better understand fusion inhibitor potency and resistance, we combined ...
2009 NOV 16 ... "The pregnane X receptor (PXR, NR1I2) regulates the expression of genes that encode drug-metabolizing enzymes and drug transporter proteins in liver and intestine. Understanding ... ligand-inducible PXR activity. Mutations in the extreme N terminus and in the PXR ligand-binding domain at positions Ser8, Ser305, Ser350, and Thr408 decrease the ability of PXR to form ... sites within the PXR protein by use of a rational, comprehensive, and systematic site-directed mutagenesis approach to generate phosphomimetic mutations (Ser/Thr -> Asp) ...
2009 NOV 23 ... drugs, so fully understanding their behavior could open up avenues for further drug development, noted Jessica Brown, a doctoral student in the Ohio State Biochemistry ... template DNA strand. The DNA strand must move from what is known as the pocket to allow binding and incorporation of the nucleotide in the correct place. By step five in ... "By moving away from the DNA, the additional space on the enzyme's active site may accommodate a distorted DNA structure," Suo said. "We are investigating that ...
2009 NOV 23 ... (log p=-0.32; polar surface area 3.88) provides prerequisites for a potential use of the drug in the treatment of neural disorders." Soukup and colleagues published ... Ellman's method at 436 nm and commercial enzymes we found that MA inhibits AChE by binding with relatively high potency to the peripheral anionic site (IC(50)=1.68 +/-0.14 1M; ...
2009 NOV 16 ... Keywords: People's Republic of China, Beijing, Antiproliferative Activity, Cancer, Drug Development, Drugs, Enzymes, Molecular Pharmacology, Molecular Therapies, Oncology, ... occurs at its transcription level that is mediated by an estrogenrelated receptor (ERR) bindingsite (-1078 to -1070 base pairs) mapped in the promoter region of UPase gene. Our ...
2009 NOV 16 ... Jolla, Antibacterial, Antibiotic, Antimicrobial Resistance, Biochemical, Biochemistry, Drug Resistance, Enzymes, Gram-Negative Bacterial Infections, Lactamase, Therapy, Treatment, ... Biochemical results show that BLIP is an extremely potent inhibitor of KPC enzymes, binding KPC-2 and KPC-3 with subnanomolar affinity. TO understand the basis of affinity and ... loop is absent, in contrast to homologous structures in which it occupies the active site. This finding and other sources of structural plasticity appear to contribute to BLIP's ...
2009 NOV 16 ... of pharmacology and director of the National Institute of Mental Health Psychoactive Drug Screening Program at UNC. "We may now have a way to predict what side effects are ... compares how similar the structures of all known drugs are to the naturally occurring binding partners -- known as ligands -- of disease targets within the cell. In a study published ... substance dimethyltrytamine (DMT), which had previously been postulated to act through a site known as the sigma-1 receptor. Using the computational approach, Roth and colleagues ...
2009 NOV 16 ... Antimicrobials, Antibiotic, Antibacterial, Therapy, Treatment, Lactamase, Enzymes, Drug Therapy, Chemotherapy, University of Liege. This article was prepared by ... enzymes, subclass B2 enzymes, such as Aeromonas hydrophila CphA, are inhibited by the binding of a second zinc ion. We crystallized A. hydrophila CphA in order to determine the ... a second zinc ion. We crystallized A. hydrophila CphA in order to determine the binding site of the inhibitory zinc ion. X-ray data from zinc-saturated crystals allowed us to solve ...
