Eli Lilly and Company

About: Eli Lilly and Company is a company organization based out in Indianapolis, Indiana, United States. It is known for research contribution in the topics: Population & Receptor. The organization has 17826 authors who have published 22835 publications receiving 946714 citations. The organization is also known as: Eli Lily.

Use of glp-1 analogs and derivatives administered peripherally in regulation of obesity

Abstract: This invention relates the use of glucagon-like peptides such as GLP-1, a GLP-1 analog, or a GLP-1 derivative in methods and compositions for reducing body weight.

Anxiolytic and Side-Effect Profile of LY354740: A Potent, Highly Selective, Orally Active Agonist for Group II Metabotropic Glutamate Receptors

Abstract: LY354740 is a conformationally constrained analog of glutamate which is a potent agonist for group II cAMP coupled metabotropic glutamate receptors (mGluRs). The discovery of this novel pharmacological agent has allowed the exploration of the functional consequences of activating group II mGluRs in vivo . In an effort to evaluate the clinical utility of LY354740 as an anxiolytic, we examined its effects in the fear potentiated startle and elevated plus maze models of anxiety and compared the results with the clinically prescribed anxiolytic diazepam. In the fear potentiated startle and elevated plus maze models, both LY354740 and diazepam produced significant anxiolytic activity (ED 50 values of 0.3 and 0.4 mg/kg p.o. for fear potentiated startle and 0.2 and 0.5 mg/kg for the elevated plus maze, respectively). The duration of pharmacological effect for LY354740 in the efficacy models was 4 to 8 hr. In contrast to diazepam, acute administration of LY354740 did not produce sedation, cause deficits in neuromuscular coordination, interact with central nervous system depressants, produce memory impairment or change convulsive thresholds at doses 100- to 1000-fold the efficacious doses in animal models of anxiety. Thus, LY354740 has anxiolytic activity in animal models that are sensitive to benzodiazepines such as diazepam. However, at anxiolytic doses in these models, LY354740 produced none of the unwanted secondary pharmacology associated with diazepam. These data indicate a functional role for group II mGluRs in fear/anxiety responses in animals and suggest that compounds in this class may be beneficial in the treatment of anxiety-related disorders in humans without the side effects seen with currently prescribed medications.

Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2−, Node-Positive, High-Risk, Early Breast Cancer (monarchE)

Abstract: PURPOSEMany patients with HR+, HER2− early breast cancer (EBC) will not experience recurrence or have distant recurrence with currently available standard therapies. However, up to 30% of patients ...

Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans

Abstract: Aggregation of amyloid-β (Aβ) as toxic oligomers and amyloid plaques within the brain appears to be the pathogenic event that initiates Alzheimer's disease (AD) lesions. One therapeutic strategy has been to reduce Aβ levels to limit its accumulation. Activation of certain neurotransmitter receptors can regulate Aβ metabolism. We assessed the ability of serotonin signaling to alter brain Aβ levels and plaques in a mouse model of AD and in humans. In mice, brain interstitial fluid (ISF) Aβ levels were decreased by 25% following administration of several selective serotonin reuptake inhibitor (SSRI) antidepressant drugs. Similarly, direct infusion of serotonin into the hippocampus reduced ISF Aβ levels. Serotonin-dependent reductions in Aβ were reversed if mice were pretreated with inhibitors of the extracellular regulated kinase (ERK) signaling cascade. Chronic treatment with an SSRI, citalopram, caused a 50% reduction in brain plaque load in mice. To test whether serotonin signaling could impact Aβ plaques in humans, we retrospectively compared brain amyloid load in cognitively normal elderly participants who were exposed to antidepressant drugs within the past 5 y to participants who were not. Antidepressant-treated participants had significantly less amyloid load as quantified by positron emission tomography (PET) imaging with Pittsburgh Compound B (PIB). Cumulative time of antidepressant use within the 5-y period preceding the scan correlated with less plaque load. These data suggest that serotonin signaling was associated with less Aβ accumulation in cognitively normal individuals.

Hplc For Pharmaceutical Scientists

Abstract: PREFACE CONTRIBUTORS PART I HPLC THEORY AND PRACTICE 1 Introduction (Yuri Kazakevich and Rosario LoBrutto) 11 Chromatography in the Pharmaceutical World 12 Chromatographic Process 13 Classification 14 History of Discovery and Early Development (1903-1933) 15 General Separation Process 16 Types of HPLC 17 HPLC Descriptors (Vr, k, N, etc) 2 HPLC Theory (Yuri Kazakevich) 21 Introduction 22 Basic Chromatographic Descriptors 23 Efficiency 24 Resolution 25 HPLC Retention 26 Retention Mechanism 27 General Column Mass Balance 28 Partitioning Model 29 Adsorption Model 210 Total and Excess Adsorption 211 Mass Balance in Adsorption Model 212 Adsorption of the Eluent Components 213 Void Volume Considerations 214 Thermodynamic Relationships 215 Adsorption-Partitioning Retention Mechanism 216 Secondary Equilibria 217 Gradient Elution Principles 218 Types of Analyte Interactions with the Stationary Phase 219 Conclusion 3 Stationary Phases (Yuri Kazakevich and Rosario LoBrutto) 31 Introduction 32 Type of Packing Material (Porous, Nonporous, Monolithic) 33 Base Material (Silica, Zirconia, Alumina, Polymers) 34 Geometry 35 Adsorbent Surface Chemistry 36 Surface of Chemically Modified Material 37 Polymer-Based Adsorbents 38 Stationary Phases for Chiral Separations 39 Columns 4 Reversed-Phase HPLC (Rosario LoBrutto and Yuri Kazakevich) 41 Introduction 42 Retention in Reversed-Phase HPLC 43 Stationary Phases for RPLC 44 Mobile Phases for RPLC 45 pH Effect on HPLC Separations 46 Effect of Organic Eluent Composition on Analyte Ionization 47 Synergistic Effect of pH, Organic Eluent, and Temperature on Ionizable Analyte Retention and Selectivity 48 Examples of Applying pH Shift and Analyte pKa Shift Rules 49 Effect of Temperature on Analyte Ionization 410 Ion-Interaction Chromatography 411 Concluding Remarks 5 Normal-Phase HPLC (Yong Liu and Anant Vailaya) 51 Introduction 52 Theory of Retention in Normal-Phase Chromatography 53 Effect of Mobile Phase on Retention 54 Selectivity 55 Applications 56 Conclusions 6 Size-Exclusion Chromatography (Yuri Kazakevich and Rosario LoBrutto) 61 Separation of the Analyte Molecules by Their Size 62 Molecular Size and Molecular Weight 63 Separation Mechanism 64 Calibration 65 Columns 66 Molecular Weight Distribution 67 Effect of Eluent 68 Effect of Temperature 69 Detectors 610 Solving Mass Balance Issues 611 Aqueous SEC Applications 7 LC/MS: Theory, Instrumentation, and Applications to Small Molecules (Guodong Chen, Li-Kang Zhang, and Birendra N Pramanik) 71 Introduction 72 Ionization Methods and LC/MS Interfaces 73 Mass Analyzers 74 Role of Instrumental Parameters on Ionization Efficiency in LC/MS 75 Effect of Mobile-Phase Composition on Ionization Efficiency in LC/MS 76 MS Interpretation 77 Practical Applications 78 Conclusions 8 Method Development (Rosario LoBrutto) 81 Introduction 82 Types of Methods 83 Defining the Method 84 Method Development Considerations 85 Method Development Approaches 86 Effect of pH on UV Absorbance 87 Analyte pKa-From an Analytical Chemist's Perspective 88 Reversed-Phase Versus Normal-Phase Separations 89 Instrument/System Considerations 810 Column Testing (Stability and Selectivity) 811 Concluding Remarks 9 Method Validation (Rosario LoBrutto and Tarun Patel) 91 Introduction 92 Validation Report 93 Revalidation 94 Assignment of Validation Parameters 95 Distinguishing Drug-Related and Non-Drug-Related Degradation Products 96 Concluding Remarks 10 Computer-Assisted HPLC and Knowledge Management (Yuri Kazakevich, Michael McBrien, and Rosario LoBrutto) 101 Introduction 102 Prediction of Retention and Simulation of Profiles 103 Optimization of HPLC Methods 104 Structure-Based Tools 105 Conclusion PART II HPLC IN THE PHARMACEUTICAL INDUSTRY 11 The Expanding Role of HPLC in Drug Discovery (Daniel B Kassel) 111 Introduction 112 Applications of HPLC/MS for Protein Identification and Characterization 113 Applications of HPLC/MS/MS in Support of Protein Chemistry 114 Applications of HPLC/MS/MS in Support of Assay Development and Screening 115 Sources of Compounds for Biological Screening 116 HPLC/MS Analysis to Support Compound Characterization 118 Higher-Throughput Purification Strategies 119 ADME Applications 1110 Fast Serial ADME Analyses Incorporating LC-MS and LC-MS/MS 1111 Parallel Approaches to Speeding ADME Analyses 1112 Automated "Intelligent" Metabolic Stability and Metabolite ID 1113 Conclusions 12 Role of HPLC in Preformulation (Irina Kazakevich) 121 Introduction 122 Initial Physicochemical Characterization (Discovery Support) 123 Chemical Stability 124 Salt Selection 125 Polymorphism 126 Preformulation Late Stage (Development Support) 127 Conclusions 13 The Role of Liquid Chromatography-Mass Spectrometry in Pharmacokinetics and Drug Metabolism (Ray Bakhtiar, Tapan K Majumdar, and Francis L S Tse) 131 Introduction 133 Tandem-Mass Spectrometry (MS/MS) 134 Sample Preparation Using an Off-Line Approach 135 Automated Sample Transfer 136 Sample Processing Using an On-Line Approach 137 Matrix Effect and Ion Suppression 138 Regulatory Requirements for LC/MS Method Validation 139 Ritalin(r): An Application of Enantioselective LC-MS/MS 1310 GleevecTM (STI571) 1311 Biomarkers 1312 Conclusions 14 Role of HPLC in Process Development (Richard Thompson and Rosario LoBrutto) 141 Responsibilities of the Analytical Chemist During Process Development 142 HPLC Separation Modes 143 Sample Preparation 144 HPLC Detectors 145 Method Development 146 In-Process Monitoring 147 Impurity Identification 148 Establishment of HPLC Selectivity by Stress Studies 149 HPLC Method Validation 1410 Technology Transfer 1411 Concluding Remarks 15 Role of HPLC During Formulation Development (Tarun S Patel and Rosario LoBrutto) 151 Introduction 152 Prerequisite for Analytical Chemists During Formulation Development 153 Properties of Drug Substance 154 Properties of Excipients 155 Impact of Excipients on Degradation of API(s) 156 Test Methods for Most Common Dosage Forms in which HPLC Is the Primary Technique 157 Forced Decomposition 158 Compatibility of Excipients with API(s) (Type and Ratio) 159 Mass Balance 1510 Summary of Assay and Related Substances 1511 Uniformity of Dosage Units 1512 Blend Uniformity (BU) 1513 Cleaning Verification 1514 Extractables/Leachables 1515 Dissolution 1516 Method Development 1517 Method Validation 1518 Testing of Samples 1519 Automation Opportunities 1520 Implementation of Alternative Technologies 1521 Challenges and Future Trends A151 Addendum (Common Functional Groups) A1511 Carbonyls A1512 Nitrogen Functional Groups A1513 Ethers, Thioethers A1514 Alkyl/Aryl Halides A1515 Hydroxyls A1516 Thiols A1517 Phenols A1518 Olefins A1519 Dimerization A15110 Ring Transformations 16 The Role of HPLC in Technical Transfer and Manufacturing (Joseph Etse) 161 Introduction 162 Prerequisites for Transfer of HPLC Methods 163 Types of Technical Transfer 164 Different Approaches for Technical Transfer and Manufacturing 165 Potential Pitfalls During Technical Transfer and Manufacturing 166 Conclusion PART III HYPHENATED TECHNIQUES AND SPECIALIZED HPLC SEPARATIONS 17 Development of Fast HPLC Methods (Anton D Jerkovich and Richard V Vivilecchia) 171 Introduction 172 Basic Theory 173 Monolithic Columns 174 Ultra-High-Pressure Liquid Chromatography 175 Separations on Chips 176 Optimizing Gradient Separations for Speed 177 Instrumental Requirements for Operating High-Efficiency Columns 178 Conclusions 18 Temperature as a Variable in Pharmaceutical Applications (Roger M Smith) 181 The Influence of Temperature on Chromatography 182 Effects on Method Transferability and Reproducibility 183 Elevated Temperature and Pharmaceutical Separations 184 Superheated Water Chromatography 186 Subambient Separations 187 Conclusion 19 LC/MS Analysis of Proteins and Peptides in Drug Discovery (Guodong Chen, Yan-Hui Liu, and Birendra N Pramanik) 191 Introduction 192 General Strategies for Analysis of Proteins/Peptides 193 Applications for Biotechnology Products and Drug Targets 194 Conclusions 20 LC-NMR Overview and Pharmaceutical Applications (Maria Victoria Silva Elipe) 201 Introduction 202 Historical Background of NMR 203 LC-NMR 204 LC-MS-NMR (or LC-NMR-MS or LC-NMR/MS) 205 Conclusions 21 Trends in Preparative HPLC (Ernst Kuesters) 211 Introduction 212 Method Development in Preparative HPLC 213 Columns and Stationary Phases 214 Choice of Preparative LC Technology 215 Detection Tools 216 Conclusion 22 Chiral Separations (Nelu Grinberg, Thomas Burakowski, and Apryll M Stalcup) 221 Introduction 222 Separation of Enantiomers Through the Formation of Diastereomers 223 Molecular Interactions 2235 Charge Transfer 224 Mixed Types of Interaction 225 Ligand Exchange 226 Chiral Mobile Phases 227 Method Development for Chiral Separation 228 Concluding Remarks CHEMICAL AND DRUG COMPOUND INDEX SUBJECT INDEX