This is the RSS news feed of one of our free news channels on LSIS - The Life Science Infromation Service. Please visit us to find a current view of this one and many more channels via our alerting push services: http://www.lsis.com/channels/?query=9 http://www.lsis.com/goto/r9/rss 2012-02-05T11:10:11+01:00 text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 Aims:? To describe the time to clinical events (death, disability, cognitive impairment and depression) in Parkinson's disease using the time course of disease status and treatment as explanatory variables. Methods:? Disease status based on the Unified Parkinson's Disease Rating Scale (UPDRS) and the time to clinical outcome events were obtained from 800 patients who initially had early Parkinson's disease. Parametric hazard models were used to describe the time to the events of interest. (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 Liquid chromatography-mass spectrometry (LC/MS) has become the method of choice for characterizing complex mixtures. These analyses often involve quantitative comparison of components in multiple samples. To achieve automated sample comparison, the components of interest must be detected and identified, and their retention times aligned and peak areas calculated. This article describes a simple pairwise iterative retention time alignment algorithm, based on the divide-and-conquer approach, for (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 Prefilled syringes and autoinjectors are becoming increasingly common for parenteral drug administration primarily due to the convenience they offer to the patients. Successful commercialization of such delivery systems requires thorough characterization of individual components. Complete understanding of various sources of variability and their ranking is essential for robust device design. In this work, we studied the impact of variability in various primary container and device components (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) Chlorine dioxide fumigation was successfully used to decontaminate a virally contaminated biotech manufacturing facility. Addressing safety, product quality, and corrosion risks were important factors in planning the (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 Animal models of experimentally induced inflammatory bowel disease (IBD) are useful for understanding more about the mechanistic basis of disease, identifying new targets for therapeutic intervention, and testing novel therapeutic agents. This unit provides detailed protocols for four of the most commonly used mouse models of experimentally induced intestinal inflammation: chemical induction of colitis by dextran sodium sulfate (DSS), hapten-induced colitis via 2,4,6-trinitrobenzene sulfonic (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 Inflammatory bowel disease (IBD), a condition that affects millions of individuals, encompasses two distinct conditions: Crohn's disease (CD) and ulcerative colitis (UC). CD is an inflammatory condition affecting any part of the digestive tract between the mouth and anus, but, most commonly, the ileum and colon. It is distinguished by the presence of granulomas in the mucosal tissue and patchy areas of transmural inflammation. UC is restricted to the colon and is manifest as continuous (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). |-| PDA J Pharm Sci Technol. |-| Dehghani H, Lawrence B, Ill RC. |-| Amgen, Cellular Resources and Biosafety Development, 1201 Amgen Court West, Seattle, WA 98119. text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA). |-| PDA J Pharm Sci Technol. |-| Skrine J. |-| Executive Director, North America, Operations Quality, Amgen. text/html http://www.sciencedaily.com ScienceDaily http://www.lsis.com/channels/?query=9 ScienceDaily (Jan. 31, 2012) A study of the cells that respond to crises in the blood system has yielded a few surprises, redrawing the 'map' of how blood cells are made in the body. See Also: Health & Medicine Immune System Anemia Lymphoma Hypertension Blood Clots Brain Tumor Reference Natural killer cell Embryonic stem cell Blood sugar Somatic cell The finding, by researchers from the Walter and Eliza Hall Institute, could have wide-ranging implications for understanding blood diseases such (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 Freeze drying, or lyophilization is widely used for biopharmaceuticals to improve the long term storage stability of labile molecules. This review examines general theory and practice of rational lyophilization of biopharmaceuticals. Formulation development involving the selection of appropriate excipients, their associated physical properties, and mechanism of action in achieving a stable drug product are primary considerations for a successful lyophilization program. There are several (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 Aims:? (1) To describe the progression of the cardinal features of Parkinson's disease (PD); (2) to investigate whether baseline PD subtypes explain disease progression; (3) to quantify the symptomatic and disease modifying effects of anti-parkinsonian treatments. Methods:? Data were available for 795 PD subjects, initially untreated, followed for up to 8 years. Cardinal features (tremor, rigidity, bradykinesia, postural instability and gait disorder (PIGD) were derived from the total (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 The aim of this study is to investigate the capability of an apolipoprotein A-I (apoA-I) mimetic with multiple amphipathic helices to form HDL-like particles in vitro and in vivo. In order to generate multivalent helices and to track the peptide mimetic, we have constructed a peptibody by fusing two tandem repeats of 4F peptide to the C-terminus of a murine IgG Fc fragment. The resultant peptidbody, mFc-2X4F, dose-dependently promoted cholesterol efflux in vitro and the efflux potency was (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 In a study designed to establish the safety of a marketed drug, interim analyses performed to detect harm can protect trial participants and the wider public before the final analysis occurs. Monitoring for harm within a safety study is different from monitoring for benefit, so techniques commonly used in an efficacy study of an experimental drug may not apply. We propose potentially more suitable techniques in this setting, including a novel spending function and conditional power. These (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 Our first generation CRTH2 and DP dual antagonists, represented by AMG 009, are more potent toward the CRTH2 receptor than to the DP receptor. Here we report our efforts in the discovery of CRTH2 and DP dual antagonists with more balanced potencies to both receptors, such as compound 15. |-| Bioorg Med Chem Lett. |-| Liu JJ, Wang Y, Johnson MG, Li AR, Shen W, Wang X, Su Y, Brown M, Van Lengerich B, Rickel E, Martin T, Budelsky A, Seitz L, Danao J, Tang HL, Collins T, Medina JC. |-| Amgen Inc., (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 Nearly 30% of currently approved recombinant therapeutic proteins are produced in Escherichia coli. Due to its well-characterized genetics, rapid growth and high-yield production, E. coli has been a preferred choice and a workhorse for expression of non-glycosylated proteins in the biotech industry. There is a wealth of knowledge and comprehensive tools for E. coli systems, such as expression vectors, production strains, protein folding and fermentation technologies, that are well tailored for (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 In anemic patients receiving myelosuppressive chemotherapy, erythropoiesis-stimulating agents (ESAs) raise hemoglobin levels and reduce transfusion requirements, but ESA-related safety concerns exist. To evaluate ESA benefits and risks in lung cancer, we conducted meta-analyses of data from controlled ESA trials conducted in lung cancer patients. Study-level analyses included controlled ESA trials reporting lung cancer mortality, identified from the 2006 Cochrane ESA report and from a (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 Replacement of the azetidine carboxylate of an S1P(1) agonist development candidate, AMG 369, with a range of acyclic head-groups led to the identification of a novel, S1P(3)-sparing S1P(1) agonist, (-)-2-amino-4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)-2-methylbutanoic acid (8c), which possessed good in vivo efficacy and pharmacokinetic properties. A 0.3mg/kg oral dose of 8c produced a statistically significant reduction in blood lymphocyte counts 24h (…) text/html http://www.biospace.com BioSpace http://www.lsis.com/channels/?query=9 (SAN DIEGO, CA) - CONVENTUS BIOMEDICAL SOLUTIONS, INC., a regulatory affairs consulting firm in Sorrento Valley, has entered its eighth year of operation in the biotech corridor of San Diego and recently added key personnel to its team. President and Principal Regulatory Consultant, Steven A. Kradjian, RAC, founded the company in 2004 after twenty-five years of experience in biotech regulatory affairs at positions including Executive Director of Regulatory and Quality Assurance at Vical, Inc., (…) text/html http://www.biospace.com BioSpace http://www.lsis.com/channels/?query=9 SOUTH SAN FRANCISCO, CA-(Marketwire - January 26, 2012) - Highlighted Links CYTK Website Cytokinetics, Incorporated (NASDAQ: CYTK) announced today that it is scheduled to report fourth quarter and year end results on Thursday, February 2, 2012 at 4:00 PM Eastern Time. Following the announcement, Cytokinetics' senior management will host a conference call at 4:30 PM Eastern Time to discuss operational and financial results and the company's outlook for the future. The conference call will be (…) text/html http://www.sciencedaily.com ScienceDaily http://www.lsis.com/channels/?query=9 ScienceDaily (Jan. 12, 2012) A team of researchers at the California Institute of Technology (Caltech) has devised a new method for making complex molecules. The reaction they have come up with should enable chemists to synthesize new varieties of a whole subclass of organic compounds called nitrogen-containing heterocycles, thus opening up new avenues for the development of novel pharmaceuticals and natural products ranging from chemotherapeutic compounds to bioactive plant materials such as (…) text/html http://www.uspto.gov/ USPTO http://www.lsis.com/channels/?query=9 United States Patent: 8101178 |-| Title: Antibodies directed to tumor necrosis factor and uses thereof |-| Inventors: Babcook; John S. (Vancouver, CA), Kang; Jaspal S. (Surrey, CA), Foord; Orit (Foster-City, CA), Green; Larry (San Francisco, CA), Feng; Xiao (Union City, CA), Klakamp; Scott (Fremont, CA), Haak-Frendscho; Mary (Newark, CA), Rathanaswami; Palaniswami (Vancouver, CA), Pigott; Craig (Cambridge, GB), Liang; Meina (Danville, CA), Lee; Yen-Wah (Newark, CA), Manchulenko; Kathy (Port (…) text/html http://www.uspto.gov/ USPTO http://www.lsis.com/channels/?query=9 United States Patent: 8101184 |-| Title: Treatment methods using Dkk-1 antibodies |-| Inventors: Li; Ji (Thousand Oaks, CA), Shen; Wenyan (Wayne, PA), Lu; Hsieng Sen (Westlake Village, CA), Richards; William Gleason (Thousand Oaks, CA) |-| Assignee: Amgen Inc. (Thousand Oaks, CA) |-| The present invention provides antibodies and immunologically functional fragments thereof that specifically bind Dkk-1 polypeptides. The subject antibodies and fragments bind with high affinity to a (…) text/html http://www.uspto.gov/ USPTO http://www.lsis.com/channels/?query=9 United States Patent: 8101612 |-| Title: Phthalazine compounds and methods of use |-| Inventors: Tasker; Andrew (Simi Valley, CA), Zhang; Dawei (Thousand Oaks, CA), Pettus; Liping H. (Thousand Oaks, CA), Rzasa; Rob M. (Ventura, CA), Sham; Kelvin K. C. (Thousand Oaks, CA), Xu; Shimin (Newbury Park, CA), Chakrabarti; Partha (Nagpur, IN) |-| Assignee: Amgen Inc. (Thousand Oaks, CA) |-| The present invention comprises a new class of compounds useful for the prophylaxis and treatment of p38 kinase (…) text/html http://www.uspto.gov/ USPTO http://www.lsis.com/channels/?query=9 United States Patent: 8101617 |-| Title: Disubstituted ureas and uses thereof in treating heart failure |-| Inventors: Morgan; Bradley Paul (South San Francisco, CA), Muci; Alex (South San Francisco, CA), Lu; Pu-Ping (South San Francisco, CA), Kraynack; Erica Anne (South San Francisco, CA), Tochimoto; Todd (South San Francisco, CA), Morgans, Jr.; David J. (South San Francisco, CA) |-| Assignee: Amgen, Inc. (Thousand Oaks, CA) |-| Certain substituted urea derivatives selectively modulate the (…) text/html http://www.biospace.com BioSpace http://www.lsis.com/channels/?query=9 Sandoz announced today that it has initiated two milestone Phase III clinical trials - one for biosimilar filgrastim (Amgen's Neupogen(R) in the US market, the other for its global pegfilgrastim development program (Amgen's Neulasta(R). The filgrastim study is to evaluate the efficacy and safety of Sandoz's biosimilar filgrastim versus Neupogen(R) in breast cancer patients eligible for myelosuppressive chemotherapy treatment. It is expected to support extension of commercialization to the (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 The endocrine FGF21 requires both FGFR and ?-Klotho for signaling. In this study, we sought to understand the inter-molecular physical interactions in the FGF21/FGFR/?-Klotho complex by deleting key regions in FGFR1c or FGF21. Deletion of the D1 and the D1-D2 linker (the D1/linker region) from FGFR1c led to ?-Klotho-independent receptor activation by FGF21, suggesting that there may be a direct interaction between FGF21 and the D1/linker region-deficient FGFR1c. Consistent with this, the (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 The in vitro binding stoichiometry of denosumab, an IgG2 fully human monoclonal therapeutic antibody, to RANK ligand was determined by multiple complementary size separation techniques with mass measuring detectors, including two solution-based techniques (size-exclusion chromatography with static light scattering detection and sedimentation velocity analytical ultracentrifugation) and a gas-phase analysis by electrospray ionization time-of-flight mass spectrometry from aqueous nondenaturing (…) text/html http://www.uspto.gov/ USPTO http://www.lsis.com/channels/?query=9 United States Patent: 8097620 |-| Title: Diazaquinolones that inhibit prolyl hydroxylase activity |-| Inventors: Allen; Jennifer R. (Newbury Park, CA), Biswas; Kaustav (Pasadena, CA), Burli; Roland (Bishop's Shortford, GB), Golden; Jennifer E. (Simi Valley, CA), Mercede; Stephanie (Thousand Oaks, CA), Tegley; Christopher M. (Thousand Oaks, CA) |-| Assignee: Amgen Inc. (Thousand Oaks, CA) |-| Compounds of Formula I are useful inhibitors of HIF prolyl hydroxylases. Compounds of Formula I have (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 BACKGROUND: Conatumumab is a fully human monoclonal agonist antibody that binds to death receptor 5 and induces apoptosis in sensitive cells. This study evaluated the safety and efficacy of doxorubicin±conatumumab as first-line systemic therapy for metastatic or locally advanced/unresectable soft-tissue sarcoma. METHODS: In Phase I, six patients received doxorubicin (75mg/m(2) with conatumumab (15mg/kg) every 3weeks. In Phase II, patients were randomised (2:1) to receive doxorubicin with (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 Osteoporosis is the most common clinical disorder of bone metabolism, and is characterised by low bone mass and deterioration of the microarchitecture of bone tissue that results in increased bone fragility and susceptibility to bone fracture.1 In the UK, it is estimated that osteoporosis affects over 3 million people and leads to 230,000 fractures per year.2 It occurs most commonly in postmenopausal women and prevalence increases markedly with age, from 2% in women at 50 years to more than (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 We report that the loop diuretic drugs bumetanide and furosemide used in the treatment of hypertension are GPR35 agonists. We utilized calcium flux, inositol phosphate accumulation, and dynamic redistribution assays to examine the pharmacology of these compounds on the human, mouse and rat GPR35. While potent on human GPR35, neither bumetanide nor furosemide were active against mouse or rat GPR35. Furthermore, the Na(+)-Cl(-) cotransporter inhibi- tors chlorothiazide and hydrochlorothiazide (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 Glass particles generated by glass dissolution and delamination of the glass container for pharmaceutical products have become a major issue in the pharmaceutical industry. The observation of glass particles in certain injectable drugs, including several protein therapeutics, has recently resulted in a number of product recalls. Glass vial surface properties have been suggested to play a critical role in glass dissolution and delamination. Surface characterization of glass container, (…) text/html http://www.biospace.com BioSpace http://www.lsis.com/channels/?query=9 Watson Pharmaceuticals Inc. (WPI) Chief Executive Officer Paul Bisaro said the company is interested in buying either a generic or brand-name drugmaker. œOur appetite for a larger transaction, it s there,  Bisaro said today at the J.P. Morgan Healthcare Conference in San Francisco. Watson, the maker of the authorized copy of Pfizer Inc. s cholesterol pill Lipitor, is looking to expand its international reach as well as the company s portfolio of brand-name drugs. Acquisitions and (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 In this report, we examine the performance of a mass spectrometry (MS)-based method for quantification of protein posttranslational modifications (PTMs) using stable isotope-labeled internal standards. Uniform labeling of proteins and highly similar behavior of the labeled vs nonlabeled analyte pairs during chromatographic separation and electrospray ionization (ESI) provide the means to directly quantify a wide range of PTMs. In the companion report (Jiang et al., Anal. Biochem., 2011), we (…) text/html http://www.biospace.com BioSpace http://www.lsis.com/channels/?query=9 CAMARILLO, Calif.-(BUSINESS WIRE)-PBS Biotech, Inc., the leading supplier of novel single-use bioreactors for the biopharmaceutical industry, announced today that George J. Morrow, former Executive Vice President, Global Commercial Operations, Amgen Inc., joined its Advisory Board. text/html http://www.biospace.com BioSpace http://www.lsis.com/channels/?query=9 Dako, a world leading independent cancer diagnostic supplier with 45 years of experience in pathology, announced today that it has entered into a development and collaboration agreement with Amgen Inc. (Nasdaq: AMGN) to develop a diagnostic test for an Amgen cancer drug candidate targeted for a rare and deadly cancer. "I am proud to announce that Dako and Amgen have succeeded in putting together a business model that supports the concurrent development of drug and diagnostics for a low (…) text/html http://www.uspto.gov/ USPTO http://www.lsis.com/channels/?query=9 United States Patent: 8093299 |-| Title: Methods of treating bowel disorders |-| Inventors: Geibel; John Peter (Branford, CT), Hebert; Steven Charles (Woodbridge, CT), Hebert, legal representative; Patricia (Woodbridge, CT), Martin; David (Camarillo, CA), Russell; Deborah A. (Newbury Park, CA) |-| Assignee: Amgen Inc. (Thousand Oaks, CA) Yale University (New Haven, CT) |-| The present invention relates to methods for treating bowel disorders using calcimimetics. text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 Metabolite identification is an important part of the drug discovery and development process. High sensitivity is necessary to identify metabolic products in vitro and in vivo. The most common method utilizes standard high-performance liquid chromatography (4.6?mm i.d. column and 1?mL/min flow rate) coupled to tandem mass spectrometry (HPLC/MS/MS). We have developed a method that utilizes a nano-LC system coupled to a high-resolution tandem mass spectrometer to identify metabolites from in (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 The discovery that certain long chain fatty acids potentiate glucose stimulated insulin secretion through the previously orphan receptor GPR40 sparked interest in GPR40 agonists as potential antidiabetic agents. Optimization of a series of ?-substituted phenylpropanoic acids led to the identification of (S)-3-(4-(4'-(trifluoromethyl)biphenyl-3-yl)methoxy)phenyl)hex-4-ynoic acid (AMG 837) as a potent GPR40 agonist with a superior pharmacokinetic profile and robust glucose-dependent (…) text/html http://www.biospace.com BioSpace http://www.lsis.com/channels/?query=9 Amgen Inc. and Celgene Corp. may dive into deal-making this year as the biggest biotechnology companies seek to return to the industry s high-growth roots. Amgen and Celgene are trying to boost investor returns that have lagged behind peers and may have to compete with traditional acquirers from the pharmaceutical industry, such as New York-based Pfizer Inc. and Bristol-Myers Squibb Co. In the past five years, the Nasdaq Biotechnology Index has increased 36 percent while Amgen, the world s (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 PURPOSE: To characterize exposure-response relationships of AMG 386 in a phase 2 study in advanced ovarian cancer for the facilitation of dose selection in future studies. METHODS: A population pharmacokinetic model of AMG 386 (N = 141) was developed and applied in an exposure-response analysis using data from patients (N = 160) with recurrent ovarian cancer who received paclitaxel plus AMG 386 (3 or (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 Clinical genetic data have shown that the product of the SCN9A gene, voltage-gated sodium ion channel Nav1.7, is a key control point for pain perception and a possible target for a next generation of analgesics. Sodium channels, however, historically have been difficult drug targets, and many of the existing structure-activity relationships (SAR) have been defined on pharmacologically modified channels with indirect reporter assays. Herein we describe the discovery, optimization, and SAR of (…) text/html http://www.uspto.gov/ USPTO http://www.lsis.com/channels/?query=9 United States Patent: 8088794 |-| Title: Substituted amide derivatives and methods of use |-| Inventors: Kim; Tae-Seong (Thousand Oaks, CA), Bauer; David (Sudbury, MA), Bellon; Steven (Wellesley, MA), Boezio; Alessandro (Somerville, MA), Booker; Shon (Thousand Oaks, CA), Choquette; Deborah (Medford, MA), D'Amico; Derin C. (Newbury Park, CA), D'Angelo; Noel (Thousand Oaks, CA), Dominguez; Celia (Los Angeles, CA), Fellows; Ingrid M. (Fresno, CA), Germain; Julie (Medford, CA), Graceffa; Russell (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 With the increased attention to quality by design (QbD) for biopharmaceutical products, there is a demand for accurate and precise quantification methods to monitor critical quality attributes (CQAs). To address this need we have developed a mass spectrometry (MS) based method to quantify a wide range of posttranslational modifications (PTMs) in recombinant proteins using stable isotope-labeled internal standard (SILIS). The SILIS was produced through metabolic labeling where (15)N was (…) text/html http://www.biospace.com BioSpace http://www.lsis.com/channels/?query=9 Among the ranks of large pharmaceutical companies this year, there was a clear standout: Bristol-Myers Squibb. Pfizer, Abbott Laboratories, and Eli Lilly all managed to notch share price increases of greater than 15%. So did Amgen, which continued to define the border between the biotechnology companies and big pharma, which it looks a bit more like every single year. text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 In a series of bradykinin B1 antagonists, we discovered that replacement of oxopiperazine acetamides with dehydro-oxopiperazine acetamides provided compounds with enhanced activity against the B1 receptor. The synthesis and SAR leading to potent analogs with reduced molecular weight will be discussed. |-| Bioorg Med Chem Lett. |-| Qian W, Chen JJ, Human J, Aya T, Zhu J, Biswas K, Peterkin T, Hungate RW, Arik L, Johnson E, Kumar G, Joseph S, Jona J, Guo HX, Wu Z. |-| Department of Chemistry (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 Structure-activity relationship (SAR) investigations of a novel class of triazolopyridazinone p38? mitogen activated protein kinase (MAPK) inhibitors are disclosed. From these studies, increased in vitro potency was observed for 2,6-disubstituted phenyl moieties and N-ethyl triazolopyridazinone cores due to key contacts with Leu108, Ala157 and Val38. Further investigation led to the identification of three compounds, 3g, 3j and 3m that are highly potent inhibitors of LPS-induced MAPKAP kinase (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 BACKGROUND: Cardiovascular events are inconclusively associated with duloxetine use in clinical trials and spontaneous reports. This analysis of cardiovascular events in relation to duloxetine use within a large health insurance database provides further data on the association. METHODS: This cohort study was conducted within a population with commercial health insurance. Adults with depression who initiated duloxetine were matched to separate cohorts of initiators of venlafaxine, selective (…) text/html http://www.ncbi.nlm.nih.gov NCBI PubMed http://www.lsis.com/channels/?query=9 p38 MAP kinase is a key enzyme in the proinflammatory response and a large number of compounds have been studied as potential therapeutic drugs. This review summarizes the bioanalytical methods used for the analysis of p38 MAP kinase inhibitors, with a special focus on sample preparation and chromatographic analysis. Biological sample extraction techniques utilized included protein precipitation, liquid-liquid extraction and SPE. Applications include determinations of compounds in a variety of (…) text/html http://www.uspto.gov/ USPTO http://www.lsis.com/channels/?query=9 United States Patent: 8084479 |-| Title: Thiazole compounds and methods of use |-| Inventors: Zeng; Qingping (Thousand Oaks, CA), Allen; John G. (Newbury Park, CA), Bourbeau; Matthew P. (Woodland Hills, CA), Dominguez; Celia (Los Angeles, CA), Fotsch; Christopher H. (Thousand Oaks, CA), Han; Nianhe (Thousand Oaks, CA), Hong; Fang-Tsao (Thousand Oaks, CA), Huang; Xin (Roslindale, MA), Lee; Matthew R. (Calabasas, CA), Li; Aiwen (Westlake Village, CA), Liu; Qingyian (Camarillo, CA), Rider; James (…)