Target inhibition of galectin-3 by inhaled TD139 in patients with idiopathic pulmonary fibrosis.

The European Respiratory Journal
Nikhil HiraniToby M Maher

Abstract

Galectin (Gal)-3 is a profibrotic β-galactoside-binding lectin that plays a key role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and IPF exacerbations. TD139 is a novel and potent small-molecule inhibitor of Gal-3.A randomised, double-blind, multicentre, placebo-controlled, phase 1/2a study was conducted to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of inhaled TD139 in 36 healthy subjects and 24 patients with IPF. Six dose cohorts of six healthy subjects were evaluated (4:2 TD139:placebo ratio) with single doses of TD139 (0.15-50 mg) and three dose cohorts of eight patients with IPF (5:3 TD139:placebo ratio) with once-daily doses of TD139 (0.3-10 mg) for 14 days.Inhaled TD139 was well tolerated with no significant treatment-related side-effects. TD139 was rapidly absorbed, with mean time taken to reach maximum plasma concentration (C max) values ranging from 0.6 to 3 h and a plasma half-life (T 1/2) of 8 h. The concentration of TD139 in the lung was >567-fold higher than in the blood, with systemic exposure predicting exposure in the target compartment. Gal-3 expression on alveolar macrophages was reduced in the 3 and 10 mg dose groups compared with placebo, with a concentration-depend...Continue Reading

References

Dec 6, 2000·The Journal of Clinical Investigation·N HattoriA F Drew
Jun 23, 2004·Cytokine & Growth Factor Reviews·James C Bonner
Oct 2, 2004·Science·Emily A PartridgeJames W Dennis
Jan 18, 2006·American Journal of Respiratory and Critical Care Medicine·Antje PrasseGernot Zissel
Mar 22, 2006·Proceedings of the National Academy of Sciences of the United States of America·Neil C HendersonTariq Sethi
Jan 30, 2007·Allergology International : Official Journal of the Japanese Society of Allergology·Yumiko NishiKoji Shirai
Jan 19, 2008·The American Journal of Pathology·Neil C HendersonTariq Sethi
Feb 6, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alison C MacKinnonTariq Sethi
Aug 3, 2010·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Dmitri V PechkovskyGernot Zissel
Oct 5, 2010·Respiratory Medicine·Nicoline M KorthagenJan C Grutters
Apr 8, 2011·American Journal of Respiratory and Critical Care Medicine·Ganesh RaghuUNKNOWN ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis
Jul 2, 2011·Lancet·Talmadge E KingMoisés Selman
Nov 19, 2011·American Journal of Respiratory and Critical Care Medicine·Alison C MackinnonTariq Sethi
Dec 6, 2011·Respiratory Medicine·Koji SakamotoYoshinori Hasegawa
Feb 22, 2013·Glycobiology·Alison C MacKinnonTariq Sethi
Nov 6, 2013·Antimicrobial Agents and Chemotherapy·Odin J NadererEtienne Dumont
May 20, 2014·The New England Journal of Medicine·Luca RicheldiUNKNOWN INPULSIS Trial Investigators
May 20, 2014·The New England Journal of Medicine·Talmadge E KingUNKNOWN ASCEND Study Group
Oct 3, 2014·Lung·Nicoline M KorthagenJan C Grutters
Jun 30, 2016·Chembiochem : a European Journal of Chemical Biology·Tamara DelaineUlf J Nilsson
Aug 25, 2016·Seminars in Thrombosis and Hemostasis·Panagiotis Flevaris, Douglas Vaughan
Dec 17, 2016·Journal of Cell Science·Kamil JastrzębskiMarta Miaczynska
Jan 6, 2017·Investigative Ophthalmology & Visual Science·Wei-Sheng ChenNoorjahan Panjwani
Mar 9, 2018·Matrix Biology : Journal of the International Society for Matrix Biology·Awen MenouBruno Crestani
May 29, 2018·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Hua ShenZhi-Nong Wang
Feb 16, 2019·The European Respiratory Journal·Pauline T LukeyToby M Maher
Aug 29, 2020·American Journal of Respiratory and Critical Care Medicine·Philip L MolyneauxToby M Maher

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Citations

Nov 13, 2020·The International Journal of Biochemistry & Cell Biology·R J SlackA C Mackinnon
Mar 24, 2021·Immunology Letters·Ivan M Srejovic, Miodrag L Lukic
Apr 13, 2021·Frontiers in Pharmacology·Pamela Velázquez-DíazYang Zhou
Apr 22, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Moez GhummanJyothi U Menon
May 29, 2021·The European Respiratory Journal·Mark G Jones, Martin Kolb
May 27, 2021·International Journal of Endocrinology·Jie-Jen LeeShih-Ping Cheng
May 18, 2021·Frontiers in Immunology·Chiel van GeffenSaeed Kolahian
Jun 4, 2021·Frontiers in Pharmacology·Bruna CaridiPatric Turowski
Aug 5, 2021·The FEBS Journal·Hans H WandallIeva Bagdonaite
Sep 17, 2021·Frontiers in Pharmacology·Duncan C HumphriesAlison C Mackinnon
Jun 16, 2021·American Journal of Respiratory Cell and Molecular Biology·Victoria A PtasinskiLynne A Murray

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