Albiglutide Needs Greater Accuracy from Remaining Shots on Goal

Total Page:16

File Type:pdf, Size:1020Kb

Albiglutide Needs Greater Accuracy from Remaining Shots on Goal November 18, 2011 Albiglutide needs greater accuracy from remaining shots on goal Evaluate Vantage Victoza is looking increasingly bullet-proof. Novo Nordisk’s once-daily GLP-1 agonist proved superior to GlaxoSmithKline’s once-weekly version, albiglutide, in reducing blood glucose while also showing significant weight loss advantages in type II diabetics. This follows a similar win for Victoza against Amylin Pharmaceuticals’ once-weekly challenger in Bydureon (Amylin scores own goal in Bydureon vs Victoza head-to- head study, March 3, 2011). Albiglutide still has a number of shots on goal – data this week from the Harmony 7 trial was the first from eight phase III studies all nearing completion – with a head-to-head against Merck & Co’s DPP-IV inhibitor Januvia probably the most significant in terms of determining albiglutide’s future role and potential in the diabetes market. Although expectations have never been that high, Glaxo’s product had an opportunity to capitalise on the setbacks to Byetta, Bydureon and Roche’s once-weekly taspoglutide – this first trial read out suggests that opportunity will be limited at best or missed altogether. Playing catch up Glaxo’s decision almost three years ago to embark on an extensive phase III programme for albiglutide, branded Syncria at the time, was seen as a bit of a gamble (Glaxo makes brave decision with phase III trials for Syncria, February 17, 2009). Safety concerns about Amylin’s twice-daily Byetta, the only approved GLP-1 agonist at the time, and the fact albiglutide had a lot of ground to make up on Bydureon and taspoglutide, suggested an uphill struggle for Glaxo’s product which was licensed from Human Genome Sciences in 2004. Although Bydureon has struggled to gain FDA approval – the regulator is due to make its latest ruling on the drug in January – and Roche has scrapped taspoglutide, Novo’s Victoza has stepped in and after a cautious start is rapidly gobbling up the GLP-1 market. Global sales of Victoza are expected to exceed $1bn this year compared to $657m for Byetta, despite Byetta’s four-year head start. Meanwhile Sanofi and Zealand Pharma’s once-daily Lyxumia (lixisenatide) has made decent clinical progress. It was recently submitted to the European authorities and should be filed shortly with the FDA. Come up short As such, albiglutide could have done with a positive result in the ‘Harmony 7’ trial, the primary endpoint of which was to show non-inferiority to Victoza. Unfortunately for Glaxo the 0.78% reduction in HbA1c – a marker of the amount of glucose in the blood – in patients receiving albiglutide failed to match the 0.99% reduction with Victoza. Furthermore, on an increasingly important secondary measure of weight loss, albiglutide again came up short, its 0.62kg average reduction in weight significantly lower than the 2.21kg weight loss using Victoza. The case for Novo’s drug to eventually be used as an obesity treatment, in both diabetic and non-diabetic patients, appears to get stronger all the time. The one positive to emerge from the trial was the safety data, with nausea and vomiting rates much lower in patients receiving albiglutide compared to those on Victoza (9.9% vs. 29.2% for nausea; 5% vs. 9.3% for vomiting). Albiglutide’s miss on non-inferiority for efficacy but cleaner safety data is very similar to the outcome of Bydureon’s Duration-6 study against Victoza. What both these agents seem to gain in tolerability they give up in efficacy. Further shots With nausea and vomiting side effects still a major barrier to using GLP-1 agonists for many patients and doctors, albiglutide’s once-weekly dosing and encouraging safety profile suggests a role may yet be found, most likely as a second-line therapy in this class. As such, data from the ensuing seven pivotal trials, details of which are displayed in the table below, need to show albiglutide in a more favourable light. Results from a trial using albiglutide in combination with Sanofi’s market-leading insulin product, Lantus, should be next, followed by the important head-to-head with Januvia. An open-label study directly comparing Glaxo’s product to Lantus should also be interesting, while the remainder of the trials mostly test albiglutide in combination with a range of standard diabetes treatments. With around 4,900 patients involved in the Harmony programme, at an estimated cost of $75m, Glaxo is certainly giving albiglutide plenty of opportunity to prove itself. With initial results from most of these trials due over the next six months, the company will not have long to wait to see if the investment was worth it. GlaxoSmithKline's 'Harmony' Phase III programme for albiglutide Patient Start Completion NCT ID Notes Enrollment Date Date May- NCT01128894 841 Compared to liraglutide (Victoza) - 'Harmony 7' Sep-11 10 Sep- NCT00976391 500 Combination with insulin glargine (Lantus) Oct-11 09 Compared to sitagliptin (Januvia) - in patients with May- NCT01098539 500 Aug-12 renal impairment 10 Jan- NCT00849017 309 Two doses compared to placebo Oct-12 09 Combination with pioglitazone (Actos), with or without Jan- NCT00849056 310 Oct-12 metformin 09 Combination with metformin, compared to sitagliptin Feb- NCT00838903 1000 (Januvia) + metformin / glimepiride + metformin / Dec-12 09 metformin alone Feb- NCT00838916 779 Compared to insulin glargine (Lantus) Dec-12 09 Combination with metformin and glimepiride, Feb- NCT00839527 685 compared to metformin + glimepiride / metformin + Dec-12 09 glimepiride + pioglitazone Total 4,924 More from Evaluate Vantage Evaluate HQ 44-(0)20-7377-0800 Evaluate Americas +1-617-573-9450 Evaluate APAC +81-(0)80-1164-4754 © Copyright 2021 Evaluate Ltd..
Recommended publications
  • Combination Use of Insulin and Incretins in Type 2 Diabetes
    Canadian Agency for Agence canadienne Drugs and Technologies des médicaments et des in Health technologies de la santé CADTH Optimal Use Report Volume 3, Issue 1C Combination Use of Insulin and July 2013 Incretins in Type 2 Diabetes Supporting Informed Decisions This report is prepared by the Canadian Agency for Drugs and Technologies in Health (CADTH). The report contains a comprehensive review of the existing public literature, studies, materials, and other information and documentation (collectively the “source documentation”) available to CADTH at the time of report preparation. The information in this report is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. The information in this report should not be used as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process, nor is it intended to replace professional medical advice. While CADTH has taken care in the preparation of this document to ensure that its contents are accurate, complete, and up to date as of the date of publication, CADTH does not make any guarantee to that effect. CADTH is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in the source documentation. CADTH is not responsible for any errors or omissions or injury, loss, or damage arising from or relating to the use (or misuse) of any information, statements, or conclusions contained in or implied by the information in this document or in any of the source documentation.
    [Show full text]
  • Efficacy and Safety of Taspoglutide Versus Sitagliptin
    Diabetes Ther (2012) 3:13 DOI 10.1007/s13300-012-0013-8 ORIGINAL RESEARCH Efficacy and Safety of Taspoglutide Versus Sitagliptin for Type 2 Diabetes Mellitus (T-Emerge 4 Trial) Richard M. Bergenstal • Adriana Forti • Jean-Louis Chiasson • Michael Woloschak • Mark Boldrin • Raffaella Balena To view enhanced content go to www.diabetestherapy-open.com Received: August 9, 2012 / Published online: November 9, 2012 Ó The Author(s) 2012. This article is published with open access at Springerlink.com ABSTRACT sitagliptin or placebo, as adjunct to metformin, in patients with inadequately Introduction: The efficacy and safety of controlled type 2 diabetes. taspoglutide, a long-acting human glucagon- Methods: In this randomized, double-blind, like peptide-1 analog, were compared with double-dummy, parallel-group trial, patients were randomized to taspoglutide 10 mg once For the T-emerge 4 Study Group. weekly (QW), 20 mg QW, 100 mg sitagliptin Study investigators listed in the Appendix. once daily (QD), or placebo for 24 weeks, ClinicalTrials.gov identifier: NCT00754988. followed by 28-week short-term and 104-week long-term extension periods. The primary R. M. Bergenstal (&) endpoint was change in glycosylated Park Nicollet International Diabetes Center, hemoglobin (HbA ) after 24 weeks. Minneapolis, MN 55416, USA 1c e-mail: [email protected] Results: In this study, 666 patients (baseline HbA , 7.96% [SD, 0.87]; fasting plasma glucose, A. Forti 1c Universidade Federal do Ceara´, Fortaleza, Brazil 9.61 mmol/L [2.56]; body weight, 92.4 kg [19.3]) were randomized to taspoglutide 10 mg J.-L. Chiasson Centre de Recherche, Centre Hospitalier de QW (n = 190), 20 mg QW (n = 198), l’Universite´ de Montre´al, Universite´ de Montre´al, 100 mg sitagliptin QD (n = 185), or placebo Montreal, QC H2Q 1T8, Canada (n = 93) for 24 weeks.
    [Show full text]
  • PYY(3-36) Analogues: Structure
    PYY(3-36) analogues: Structure- activity relationships in energy homeostasis A thesis submitted for the degree of Doctor of Philosophy, Imperial College London 2011 Iain David Pritchard Section of Investigative Medicine Division of Diabetes, Endocrinology and Metabolism Department of Medicine Imperial College London Abstract The developed world is currently in the grip of an obesity epidemic. As a result, there is much ongoing research into the development of an effective anti-obesity agent. Peptide YY (PYY) is a 36 amino acid gastro-intestinal hormone released post- prandially by L-cells in the gastro-intestinal tract in proportion to the calorie content of a meal. The predominant form of the hormone found in circulation is the truncated PYY(3-36). Administration of PYY(3-36) at physiological doses to humans has been shown to reduce food intake. However, due to enzymatic degradation these effects are short lived, reducing the hormone’s utility as an anti-obesity pharmaceutical agent. A series of analogues of PYY(3-36) were designed either with amino acid substitutions in specific parts of the peptide sequence and/or with chemical modifications to the native sequence with the aim of increasing resistance to enzymatic activity whilst retaining or even enhancing the peptide’s bioactivity. The analogues were tested for resistance to degradation by different proteolytic enzymes in comparison to natural PYY(3-36). Their affinity to the Y2 receptor, for which PYY(3-36) is a natural agonist was then investigated. Finally, the effects of peripheral administration of selected analogues on food intake in overnight fasted mice were investigated.
    [Show full text]
  • Sanofi Forced to Defend Lantus' Safety Again
    June 18, 2010 Sanofi forced to defend Lantus' safety again Evaluate Vantage Reports that your most valuable product could increase the risk of cancer would put any company on the back foot. This is the position Sanofi-Aventis found itself in today following fresh allegations that its long-acting insulin, Lantus, the world’s biggest selling single insulin product, increased the risk of cancer in diabetics. Shares in the French healthcare giant fell as much as 7% in early trading today to €47.61 before recovering gradually as the company and multiple analysts tried to downplay the significance of a new Italian study published in the Diabetes Care journal. Those sensing déjà vu will remember similarly damaging studies in Diabetologia exactly 12 months ago (Sanofi brought low by Lantus cancer rumours, June 26, 2009). The Diabetologia studies have since been largely discredited and Lantus prescriptions were not materially affected (see table below). Nevertheless, Sanofi now has another major PR job on its hands to protect Lantus from increasing competition from insulin giant, Novo Nordisk. The American Diabetes Association (ADA) conference next week is warming up nicely. Valuable analysis? A group of Florence-based researchers studied the records of 1,500 diabetics going back six years and focused on the possible reasons why 112 of them developed cancer. A criticism of similar analysis showing Lantus to be perfectly safe has been that patients were only monitored for a short time so this six year period is important, given the time it takes for cancer to develop. Taking into account mitigating factors such as co-morbidity, dose and length of treatment, the results suggest a statistically significant 3.7x increase risk of cancer in patients receiving a high dose of Lantus.
    [Show full text]
  • Hypoglycemia & Hyperglycemia
    A Stepped Approach to Prescribing for Type 2 Diabetes Glycemic Control Faculty Lenora Lorenzo DNP, BC- FNP/GNP/ ADM, CDE, FAANP Primary Care Provider Team Leader Chronic Disease Management Veterans Health Affairs Pacific Island Health Care System, Hawai’i Adjunct Faculty, University of Hawai’i American Association of Nurse Practitioners Region 9 Director Arizona, California, Nevada, Hawai’i & U.S. Pacific Territories (Guam, American Samoa & the Marianna Islands) Faculty Declarations Dr. Lorenzo declares that in the past 12 months she has nothing to disclose. Learning Objectives Discuss relevant principles of physiology, pharmakokinetics and pharmocodynamics for Type 2 Diabetes (T2DM) glycemic control. Give rationale for selecting drugs of choice for T2 DM glycemic control, including evidence based guidelines. Identify the goals of therapy for T2DM glycemic control, desired effects and evaluation of patient response, including management of adverse reactions. By 2020, 1 of every 2 Americans could have Diabetes or Prediabetes United Health Center for Health Reform & Modernization. (2010). The United States of diabetes. Retrieved from http://www.unitedhealthgroup.com/hrm/unh_workingpaper5.pdf We Have an Epidemic of 2010 26mil Diabetes !! 2008 24mil Pathogenesis of Type 2 Diabetes Beta Cell Failure and Insulin Resistance Insulin Resistance + Genes Beta-cell Failure Environment Relative Deficiency in Insulin Type 2 Diabetes Adapted from Kahn CR. Diabetes. 1994;43:1066–1084. Natural History of Type 2 Diabetes Progression: Beta Cell Failure and Insulin Resistance Pre Diabetes 350 Postmeal glucose 250 Glucose Fasting glucose (mg/dL) 150 50 IFG IGT 300 Insulin resistance Relative 200 Function (%) 100 At risk for Insulin level diabetes Beta-cell failure 0 -10 -5 0 5 10 15 20 25 30 Years of diabetes Adapted from Kendall D, Bergenstal R.
    [Show full text]
  • Science Report 2010
    Science Report 2010 Profil Institut für Stoffwechselforschung GmbH Hellersbergstrasse 9 41460 Neuss www.profil.com Summary Scientific Publications Original Articles 11 (ΣIF 2009 : 32,876) Reviews 6 (ΣIF 2009 : 9,880) Letters and Comments 2 (ΣIF 2009 : 13,269) Cumulative Impact Factor 56,025 Habilitation 1 Scientific Congress Presentations Oral Presentations 12 Poster Presentations 24 Advanced Training Courses Science Sessions 9 Trainings with External Participants 6 Scientific Communication Newspaper articles 8 Granted Research Projects 3 Awards & Appointments 3 2 Scientific Publications Original Articles 1. Kapitza C , Zdravkovic M, Zijlstra E , Segel S, Heise T , Flint A Effect of three different injection sites on the pharmacokinetics of the once-daily human GLP-1 analogue liraglutide. J Clin Pharmacol , in press, 2010 IF 2009 : 3,442 2. Bonadonna RC, Heise T , Arbet-Engels C, Kapitza C , Avogaro A, Grimsby J, Zhi J, Grippo JF, Balena R, Piragliatin (RO4389620), a novel glucokinase activator, lowers plasma glucose both in the postabsorptive state and after a glucose challenge in patients with type 2 diabetes mellitus: a mechanistic study. J Clin Endocrinol Metab , 95(11):5028-36, 2010 IF 2009 : 6,202 3. Arnolds S , Rave K , Hövelmann U , Fischer A, Sert-Langeron C, Heise T Insulin glulisine has a faster onset of action compared with insulin aspart in healthy volunteers. Exp Clin Endocrinol Diabetes , 118(9):662-4, 2010 IF 2009 : 1,685 4. Ratner R, Nauck M, Kapitza C , Asnaghi V, Boldrin M, Balena R Safety and tolerability of high doses of taspoglutide: a once weekly human GLP-1 analogue in diabetic patients treated with metformin: a randomized double-blind placebo-controlled study.
    [Show full text]
  • A Meta-Analysis Comparing Clinical Effects of Short
    A meta-analysis comparing clinical effects of short- or long-acting GLP-1 receptor agonists versus insulin treatment from head-to-head studies in type 2 diabetic patients M. S. Abd El Aziz, M. Kahle, J. J. Meier, M. A. Nauck Division of Diabetology, Department of Internal Medicine I, St. Josef-Hospital (Ruhr- University Bochum), Bochum, Germany Correspondence: Prof. Dr. med. Michael Nauck, Division of Diabetology, Department of Internal Medicine I, St. Josef-Hospital, Ruhr-University Bochum Gudrunstraße 56, D-44791 Bochum, Germany Tel. +49-234-509 6332 Fax +49-234-509 2714 E-mail: [email protected] Accepted Article This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/cup.12804 ABSTRACT Aims: To study differences in clinical outcomes between initiating glucagon-like peptide-1 receptor agonist (GLP-1 RAs) vs. insulin treatment in patients with type 2 diabetes treated with oral glucose-lowering medications (OGLM). Methods: Prospective, randomized trials comparing GLP-1 RA and insulin treatment head- to-head as add-on to OGLM were identified (PubMed). Differences from baseline values were compared for HbA1c, fasting plasma glucose, body weight, blood pressure, heart rate and lipoproteins. Proportions of patients reporting hypoglycaemic episodes were compared. Results: Of 712 publications identified, 23 describing 19 clinical trials were included in the meta-analysis. Compared to insulin, GLP-1 RAs reduced HbA1c more effectively (Δ - 0.17 %, p < 0.0001).
    [Show full text]
  • Structure and Dynamics of Semaglutide and Taspoglutide Bound GLP-1R-Gs Complexes Xin Zhang1, Matthew J
    bioRxiv preprint doi: https://doi.org/10.1101/2021.01.12.426449; this version posted January 13, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Structure and dynamics of semaglutide and taspoglutide bound GLP-1R-Gs complexes Xin Zhang1, Matthew J. Belousoff1, Yi-Lynn Liang1^, Radostin Danev2*, Patrick M. Sexton1*, Denise Wootten1,3* 1. Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville 3052, Victoria, Australia 2. Graduate School of Medicine, University of Tokyo, S402, 7-3-1 Hongo, Bunkyo-ku, 113-0033 Tokyo, Japan 3. Lead contact ^Current address: Confo Therapeutics, Technologiepark 94, Ghent (Zwijnaarde) 9052, Belgium. *Address for correspondence: Denise Wootten ([email protected]) Patrick Sexton ([email protected]) Radostin Danev ([email protected]) KEYWORDS Glucagon-like pepetide-1 receptor, cryo-electron microscopy, GPCRs, GPCR dynamics bioRxiv preprint doi: https://doi.org/10.1101/2021.01.12.426449; this version posted January 13, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. SUMMARY The glucagon-like peptide-1 receptor (GLP-1R) regulates insulin secretion, carbohydrate metabolism and appetite, and is an important target for treatment of type II diabetes and obesity. Multiple GLP-1R agonists have entered into clinical trials, such as semaglutide, progressing to approval. Others, including taspoglutide, failed through high incidence of side-effects or insufficient efficacy. GLP-1R agonists have a broad spectrum of signalling profiles.
    [Show full text]
  • The Fate of Taspoglutide, a Weekly GLP-1 Receptor Agonist, Versus Twice-Daily Exenatide for Type 2 Diabetes the T-Emerge 2 Trial
    Clinical Care/Education/Nutrition/Psychosocial Research ORIGINAL ARTICLE The Fate of Taspoglutide, a Weekly GLP-1 Receptor Agonist, Versus Twice-Daily Exenatide for Type 2 Diabetes The T-Emerge 2 Trial 1 5 JULIO ROSENSTOCK, MD MARK BOLDRIN, MS low risk of hypoglycemia (1). The most 2 6 BOGDAN BALAS, MD ROBERT RATNER, MD 3 2 common adverse events with exenatide BERNARD CHARBONNEL, MD RAFFAELLA BALENA, MD 4 and liraglutide are gastrointestinal distur- GEREMIA B. BOLLI, MD FOR THE T-EMERGE 2STUDY GROUP* bances such as nausea (8–44 and 8–35%, respectively) and vomiting (4–13 and 7– 12%, respectively), which have limited OBJECTIVEdTaspoglutide is a long-acting glucagon-like peptide 1 receptor agonist devel- fi their use and adherence in clinical prac- oped for treatment of type 2 diabetes. The ef cacy and safety of once-weekly taspoglutide was – compared with twice-daily exenatide. tice (2 5). The investigational GLP-1 receptor ag- RESEARCH DESIGN AND METHODSdOverweight adults with inadequately con- onist taspoglutide has 93% homology with trolled type 2 diabetes on metformin 6 a thiazolidinedione were randomized to subcutaneous endogenous GLP-1 and was considered to taspoglutide 10 mg weekly (n = 399), taspoglutide 20 mg weekly (n = 398), or exenatide 10 mg have potency equivalent to GLP-1 (6). In twice daily (n = 392) in an open-label, multicenter trial. The primary end point was change in short-term phase 2 clinical studies, once- HbA1c after 24 weeks. weekly taspoglutide demonstrated mean- ingful antihyperglycemic and weight loss RESULTSdMean baseline HbA1c was 8.1%. Both doses of taspoglutide reduced HbA1c sig- nificantly more than exenatide (taspoglutide 10 mg: –1.24% [SE 0.09], difference –0.26, 95% CI effects (7,8).
    [Show full text]
  • Benefits and Harms of Once-Weekly Glucagon-Like Peptide-1
    This online-first version will be replaced with a final version when it is included in the issue. The final version may differ in small ways. Annals of Internal Medicine REVIEW Benefits and Harms of Once-Weekly Glucagon-like Peptide-1 Receptor Agonist Treatments A Systematic Review and Network Meta-analysis Francesco Zaccardi, MD; Zin Zin Htike, MD; David R. Webb, PhD; Kamlesh Khunti, PhD; and Melanie J. Davies, MD Background: Once-weekly glucagon-like peptide-1 receptor exenatide and albiglutide for fasting plasma glucose (–0.7 agonists (GLP-1RAs) are new drugs for the treatment of type 2 mmol/L [CI, –1.1 to –0.2 mmol/L]; –12.6 mg/dL [CI, –19.8 to –3.6 diabetes. mg/dL]), and taspoglutide, 20 mg, and dulaglutide, 0.75 mg, for body weight (–1.5 kg [CI, –2.2 to –0.8]). Clinically marginal or no Purpose: To summarize evidence for the cardiometabolic effi- differences were found for blood pressure, blood lipid levels, cacy and adverse effects of once-weekly GLP-1RAs in adults with and C-reactive protein levels. Once-weekly exenatide increased type 2 diabetes. heart rate compared with albiglutide and dulaglutide (1.4 to 3.2 Data Sources: Electronic databases (PubMed, Web of Science, beats/min). Among once-weekly GLP-1RAs, the risk for hypogly- Cochrane Central Register of Controlled Trials, U.S. Food cemia was similar, whereas taspoglutide, 20 mg, had the great- and Drug Administration, European Medicines Agency, est risk for nausea (odds ratios, 1.9 to 5.9). ClinicalTrials.gov) and congress abstracts from inception Limitation: Data were unavailable for semaglutide, definitions through 26 September 2015.
    [Show full text]
  • Metabolic Disease
    Metabolic Disease Metabolic diseases is defined by a constellation of interconnected physiological, biochemical, clinical, and metabolic factors that directly increases the risk of cardiovascular disease, type 2 diabetes mellitus, and all cause mortality. Associated conditions include hyperuricemia, fatty liver (especially in concurrent obesity) progressing to nonalcoholic fatty liver disease, polycystic ovarian syndrome (in women), erectile dysfunction (in men), and acanthosis nigricans. Metabolic disease modeling is an essential component of biomedical research and a mandatory prerequisite for the treatment of human disease. Somatic genome editing using CRISPR/Cas9 might be used to establish novel metabolic disease models. www.MedChemExpress.com 1 Metabolic Disease Inhibitors & Modulators (-)-(S)-Equol (-)-Fucose Cat. No.: HY-100583 (6-Desoxygalactose; L-(-)-Fucose; L-Galactomethylose) Cat. No.: HY-N1480 Bioactivity: (-)-(S)-Equol is a high affinity ligand for estrogen receptor Bioactivity: (-)-Fucose is classified as a member of the hexoses, plays a role in A and B blood group antigen substructure β with a Ki of 0.73 nM. determination, selectin-mediated leukocyte-endothelial adhesion, and host-microbe interactions. Purity: 99.82% Purity: >98% Clinical Data: No Development Reported Clinical Data: No Development Reported Size: 10mM x 1mL in DMSO, Size: 10mM x 1mL in DMSO, 5 mg, 10 mg, 25 mg, 50 mg 100 mg (-)-PX20606 trans isomer (24R)-MC 976 ((-)-PX-102 trans isomer; (-)-PX-104) Cat. No.: HY-100443B Cat. No.: HY-15267A Bioactivity: (-)-PX20606 trans isomer is a FXR agonist with EC50s of 18 Bioactivity: (24R)-MC 976 is a Vitamin D3 derivative. and 29 nM for FXR in FRET and M1H assay, respectively.
    [Show full text]
  • (INN) for Biological and Biotechnological Substances
    WHO/EMP/RHT/TSN/2019.1 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) 2019 WHO/EMP/RHT/TSN/2019.1 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) 2019 International Nonproprietary Names (INN) Programme Technologies Standards and Norms (TSN) Regulation of Medicines and other Health Technologies (RHT) Essential Medicines and Health Products (EMP) International Nonproprietary Names (INN) for biological and biotechnological substances (a review) FORMER DOCUMENT NUMBER: INN Working Document 05.179 © World Health Organization 2019 All rights reserved. Publications of the World Health Organization are available on the WHO website (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications –whether for sale or for non-commercial distribution– should be addressed to WHO Press through the WHO website (www.who.int/about/licensing/copyright_form/en/index.html). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned.
    [Show full text]