Experimental autotaxin inhibitors for the treatment of idiopathic pulmonary fibrosis

References

• Richeldi L, Collard HR, Jones MG. Idiopathic pulmonary fibrosis. Lancet (London, England). 2017;389:1941–1952. doi: 10.1016/S0140-6736(17)30866-8
   PubMed Web of Science ®Google Scholar
• Moss BJ, Ryter SW, Rosas IO. Pathogenic mechanisms underlying idiopathic pulmonary fibrosis. Annu Rev Pathol. 2022;17(1):515–546. doi: 10.1146/annurev-pathol-042320-030240
   PubMedGoogle Scholar
• Collard HR, Ryerson CJ, Corte TJ, et al. Acute exacerbation of idiopathic pulmonary fibrosis. An international working group report. Am J Respir Crit Care Med. 2016;194(3):265–275. doi: 10.1164/rccm.201604-0801CI
   PubMed Web of Science ®Google Scholar
• Raghu G, Rochwerg B, Zhang Y, et al. An official ATS/ERS/JRS/ALAT clinical practice guideline: Treatment of idiopathic pulmonary fibrosis: An update of the 2011 clinical practice guideline. Am J Respir Crit Care Med. 2015;192(2):e3–e19. doi: 10.1164/rccm.201506-1063ST
   PubMed Web of Science ®Google Scholar
• King TE, Bradford WZ, Castro-Bernardini S, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2083–2092. doi: 10.1056/NEJMoa1402582
   PubMed Web of Science ®Google Scholar
• Richeldi L, du Bois RM, Raghu G, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2071–2082. doi: 10.1056/NEJMoa1402584
   PubMed Web of Science ®Google Scholar
• Ogura T, Kitamura H. Tolerability of treatment with pirfenidone or nintedanib for pulmonary fibrosis in the real world. Respirology. 2017;22(6):1051–1052. doi: 10.1111/resp.13059
   PubMed Web of Science ®Google Scholar
• Fernandez IE, Eickelberg O. New cellular and molecular mechanisms of lung injury and fibrosis in idiopathic pulmonary fibrosis. Lancet (London, England). 2012;380:680–688. doi: 10.1016/S0140-6736(12)61144-1
   PubMed Web of Science ®Google Scholar
• Masuda A, Fujii T, Iwasawa Y, et al. Serum autotaxin measurements in pregnant women: application for the differentiation of normal pregnancy and pregnancy-induced hypertension. Clin Chim Acta. 2011;412(21–22):1944–1950. doi: 10.1016/j.cca.2011.06.039
   PubMed Web of Science ®Google Scholar
• Tokumura A, Majima E, Kariya Y, et al. Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase. J Biol Chem. 2002;277(42):39436–39442. doi: 10.1074/jbc.M205623200
   PubMed Web of Science ®Google Scholar
• Kanda H, Newton R, Klein R, et al. Autotaxin, a lysophosphatidic acid-producing ectoenzyme, promotes lymphocyte entry into secondary lymphoid organs. Nat Immunol. 2008;9(4):415. doi: 10.1038/ni1573
   PubMed Web of Science ®Google Scholar
• Matas-Rico E, Frijlink E, van der Haar Àvila I, et al. Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8+ T cells. Cell Rep. 2021;37(7):110013. doi: 10.1016/j.celrep.2021.110013
   PubMed Web of Science ®Google Scholar
• Umezu-Goto M, Kishi Y, Taira A, et al. Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. J Cell Bio. 2002;158(2):227–233. doi: 10.1083/jcb.200204026
   PubMed Web of Science ®Google Scholar
• Hoelzinger DB, Mariani L, Wies J, et al. Gene expression profile of glioblastoma multiforme invasive phenotype points to new therapeutic targets. Neoplasia. 2005;7(1):7. doi: 10.1593/neo.04535
   PubMed Web of Science ®Google Scholar
• Brindley DN, Tang X, Meng G, et al. Role of adipose tissue-derived autotaxin, Lysophosphatidate signaling, and inflammation in the progression and treatment of breast cancer. Int J Mol Sci. 2020;21(16):1–22. doi: 10.3390/ijms21165938
   Web of Science ®Google Scholar
• Umezu-Goto M, Tanyi J, Lahad J, et al. Lysophosphatidic acid production and action: validated targets in cancer? J Cell Biochem. 2004;92(6):1115–1140. doi: 10.1002/jcb.20113
   PubMed Web of Science ®Google Scholar
• Kaffe E, Katsifa A, Xylourgidis N, et al. Hepatocyte autotaxin expression promotes liver fibrosis and cancer. Hepatology. 2017;65(4):1369–1383. doi: 10.1002/hep.28973
   PubMed Web of Science ®Google Scholar
• Deken MA, Niewola-Staszkowska K, Peyruchaud O, et al. Characterization and translational development of IOA-289, a novel autotaxin inhibitor for the treatment of solid tumors. Immuno-Oncology Technol. 2023;18:18. doi: 10.1016/j.iotech.2023.100384
   Google Scholar
• Houben AJS, Moolenaar WH. Autotaxin and LPA receptor signaling in cancer. Cancer Metastasis Rev. 2011;30(3–4):557–565. doi: 10.1007/s10555-011-9319-7
   PubMed Web of Science ®Google Scholar
• Nam SW, Clair T, Campo CK, et al. Autotaxin (ATX), a potent tumor motogen, augments invasive and metastatic potential of ras-transformed cells. Oncogene. 2000;19(2):241–247. doi: 10.1038/sj.onc.1203263
   PubMed Web of Science ®Google Scholar
• Tager AM, LaCamera P, Shea BS, et al. The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak. Nat Med. 2008;14(1):45–54. doi: 10.1038/nm1685
   PubMed Web of Science ®Google Scholar
• Oikonomou N, Mouratis MA, Tzouvelekis A, et al. Pulmonary autotaxin expression contributes to the pathogenesis of pulmonary fibrosis. Am J Respir Cell Mol Biol. 2012;47:566–574
   PubMed Web of Science ®Google Scholar
• Kremer AE, Martens JJWW, Kulik W, et al. Lysophosphatidic acid is a potential mediator of cholestatic pruritus. Gastroenterology. 2010;139(3):1008–1018.e1. doi: 10.1053/j.gastro.2010.05.009
   PubMed Web of Science ®Google Scholar
• Sevastou I, Kaffe E, Mouratis MA, et al. Lysoglycerophospholipids in chronic inflammatory disorders: the PLA(2)/LPC and ATX/LPA axes. Biochim Biophys Acta. 2013;1831(1):42–60. doi: 10.1016/j.bbalip.2012.07.019
   PubMed Web of Science ®Google Scholar
• Barbayianni E, Kaffe E, Aidinis V, et al. Autotaxin, a secreted lysophospholipase D, as a promising therapeutic target in chronic inflammation and cancer. Prog Lipid Res. 2015;58:76–96. doi: 10.1016/j.plipres.2015.02.001
   PubMed Web of Science ®Google Scholar
• Zhang C, Liu Y, Zhou Q, et al. Recent research advances in ATX inhibitors: an overview of primary literature. Bioorg Med Chem. 2023;90:90. doi: 10.1016/j.bmc.2023.117374
   Web of Science ®Google Scholar
• Stracke ML, Krutzsch HC, Unsworth EJ, et al. Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. J Biol Chem. 1992;267(4):2524–2529. doi: 10.1016/S0021-9258(18)45911-X
   PubMed Web of Science ®Google Scholar
• Perrakis A, Moolenaar WH. Autotaxin: structure-function and signaling. J Lipid Res. 2014;55(6):1010–1018. doi: 10.1194/jlr.R046391
   PubMed Web of Science ®Google Scholar
• Castagna D, Budd DC, MacDonald SJF, et al. Development of autotaxin inhibitors: an overview of the patent and primary literature. J Med Chem. 2016;59(12):5604–5621. doi: 10.1021/acs.jmedchem.5b01599
   PubMed Web of Science ®Google Scholar
• Giganti A, Rodriguez M, Fould B, et al. Murine and Human Autotaxin α, β, and γ Isoforms. J Biol Chem. 2008;283(12):7776–7789. doi: 10.1074/jbc.M708705200
   PubMed Web of Science ®Google Scholar
• Houben AJS, Van Wijk XMR, Van Meeteren LA, et al. The polybasic insertion in autotaxin α confers specific binding to heparin and cell surface heparan sulfate proteoglycans. J Biol Chem. 2013;288(1):510–519. doi: 10.1074/jbc.M112.358416
   PubMed Web of Science ®Google Scholar
• Hashimoto T, Okudaira S, Igarashi K, et al. Identification and biochemical characterization of a novel autotaxin isoform, ATX , with a four-amino acid deletion. J Biochem. 2012;151(1):89–97. doi: 10.1093/jb/mvr126
   PubMed Web of Science ®Google Scholar
• Liu S, Murph M, Panupinthu N, et al. ATX-LPA receptor axis in inflammation and cancer. Cell Cycle. 2009;8(22):3695. doi: 10.4161/cc.8.22.9937
   PubMed Web of Science ®Google Scholar
• Aikawa S, Hashimoto T, Kano K, et al. Lysophosphatidic acid as a lipid mediator with multiple biological actions. J Biochem. 2015;157(2):81–89. doi: 10.1093/jb/mvu077
   PubMed Web of Science ®Google Scholar
• Geraldo LHM, Spohr TDS, Amaral RD, et al. Role of lysophosphatidic acid and its receptors in health and disease: novel therapeutic strategies. Signal Transduct Target Ther. 2021;6(1):1–18. doi: 10.1038/s41392-020-00367-5
   PubMed Web of Science ®Google Scholar
• Tager AM. Autotaxin emerges as a therapeutic target for idiopathic pulmonary fibrosis: limiting fibrosis by limiting lysophosphatidic acid synthesis. Am J Respir Cell Mol Biol. 2012;47(5):563–565. doi: 10.1165/rcmb.2012-0235ED
   PubMed Web of Science ®Google Scholar
• Huang LS, Fu P, Patel P, et al. Lysophosphatidic acid receptor–2 deficiency confers protection against bleomycin-induced lung injury and fibrosis in mice. Am J Respir Cell Mol Biol. 2013;49(6):912–922. doi: 10.1165/rcmb.2013-0070OC
   PubMed Web of Science ®Google Scholar
• Swaney JS, Chapman C, Correa LD, et al. A novel, orally active LPA 1 receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. Br J Pharmacol. 2010;160(7):1699–1713. doi: 10.1111/j.1476-5381.2010.00828.x
   PubMed Web of Science ®Google Scholar
• Yin Z, Watsky MA. Chloride channel activity in human lung fibroblasts and myofibroblasts. Am J Physiol Lung Cell Mol Physiol. 2005;288(6):L1110–L1116. doi: 10.1152/ajplung.00344.2004
   PubMed Web of Science ®Google Scholar
• Funke M, Zhao Z, Xu Y, et al. The lysophosphatidic acid receptor LPA1 promotes epithelial Cell apoptosis after lung injury. Am J Respir Cell Mol Biol. 2012;46(3):355. doi: 10.1165/rcmb.2010-0155OC
   PubMed Web of Science ®Google Scholar
• Ninou I, Magkrioti C, Aidinis V. Autotaxin in pathophysiology and pulmonary fibrosis. Front Med. 2018;5:358630. doi: 10.3389/fmed.2018.00180
   Web of Science ®Google Scholar
• Xu MY, Porte J, Knox AJ, et al. Lysophosphatidic acid induces αvβ6 integrin-mediated TGF-β activation via the LPA2 receptor and the small G Protein Gαq. Am J Pathol. 2009;174(4):1264. doi: 10.2353/ajpath.2009.080160
   PubMed Web of Science ®Google Scholar
• Magkrioti C, Aidinis V. Autotaxin and lysophosphatidic acid signalling in lung pathophysiology. World J Respirol. 2013;3(3):77. http://www.wjgnet.com/
   Google Scholar
• Mulholland S, Adamali H, Barratt SL. Inhibitors of the autotaxin-lysophosphatidic acid axis and their potential in the treatment of interstitial lung disease: Current perspectives. Clin Pharmacol. 2020;12:97. doi: 10.2147/CPAA.S228362
   PubMedGoogle Scholar
• Albers HMHG, Hendrickx LJD, Van Tol RJP, et al. Structure-based design of novel boronic acid-based inhibitors of autotaxin. J Med Chem. 2011;54(13):4619–4626. doi: 10.1021/jm200310q
   PubMed Web of Science ®Google Scholar
• Hausmann J, Kamtekar S, Christodoulou E, et al. Structural basis of substrate discrimination and integrin binding by autotaxin. Nat Struct Mol Biol. 2011;18(2):198–204. doi: 10.1038/nsmb.1980
   PubMed Web of Science ®Google Scholar
• Ninou I, Kaffe E, Müller S, et al. Pharmacologic targeting of the ATX/LPA axis attenuates bleomycin-induced pulmonary fibrosis. Pulm Pharmacol Ther. 2018;52:32–40. doi: 10.1016/j.pupt.2018.08.003
   PubMed Web of Science ®Google Scholar
• Lei H, Jia F, Guo M, et al. The classified progression in binding modes ofAutotaxin (atx) inhibitors. Biomed J Sci Tech Res. 2018;7(3):001–003. doi: 10.26717/BJSTR.2018.07.001496
   Google Scholar
• Salgado-Polo F, Fish A, Matsoukas MT, et al. Lysophosphatidic acid produced by autotaxin acts as an allosteric modulator of its catalytic efficiency. J Biol Chem. 2018;293(37):14312–14327. doi: 10.1074/jbc.RA118.004450
   PubMed Web of Science ®Google Scholar
• Clark JM, Salgado-Polo F, Macdonald SJF, et al. Structure-based design of a novel class of autotaxin inhibitors based on endogenous allosteric modulators. J Med Chem. 2022;65(8):6338–6351. doi: 10.1021/acs.jmedchem.2c00368
   PubMed Web of Science ®Google Scholar
• Salgado-Polo F, Borza R, Matsoukas MT, et al. Autotaxin facilitates selective LPA receptor signaling. Cell Chem Biol. 2023;30(1):69–84.e14. doi: 10.1016/j.chembiol.2022.12.006
   PubMed Web of Science ®Google Scholar
• Tanaka M, Okudaira S, Kishi Y, et al. Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid. J Biol Chem. 2006;281(35):25822–25830. doi: 10.1074/jbc.M605142200
   PubMed Web of Science ®Google Scholar
• Ongenaert M, Dupont S, Blanqué R, et al. Strong reversal of the lung fibrosis disease signature by autotaxin inhibitor GLPG1690 in a mouse model for IPF. Eur Respir J. 2016;48:OA4540.
   Web of Science ®Google Scholar
• van der Aar E, Desrivot J, Dupont S, et al. Safety, pharmacokinetics, and pharmacodynamics of the autotaxin Inhibitor GLPG1690 in healthy subjects: phase 1 randomized trials. J Clin Pharmacol. 2019;59(10):1366–1378. doi: 10.1002/jcph.1424
   PubMed Web of Science ®Google Scholar
• Maher TM, van der Aar EM, Van de Steen O, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of GLPG1690, a novel autotaxin inhibitor, to treat idiopathic pulmonary fibrosis (FLORA): a phase 2a randomised placebo-controlled trial. Lancet Respir Med. 2018;6(8):627–635. doi: 10.1016/S2213-2600(18)30181-4
   PubMed Web of Science ®Google Scholar
• Maher TM, Kreuter M, Lederer DJ, et al. Rationale, design and objectives of two phase III, randomised, placebo-controlled studies of GLPG1690, a novel autotaxin inhibitor, in idiopathic pulmonary fibrosis (ISABELA 1 and 2). BMJ Open Respir Res. 2019;6(1):6. doi: 10.1136/bmjresp-2019-000422
   Web of Science ®Google Scholar
• Maher TM, Ford P, Brown KK, et al. Ziritaxestat, a novel autotaxin inhibitor, and lung function in idiopathic pulmonary fibrosis: the ISABELA 1 and 2 randomized clinical trials. JAMA. 2023;329(18):1567–1578. doi: 10.1001/jama.2023.5355
   PubMed Web of Science ®Google Scholar
• Lee G, Kang S-U, Ryou J-H, et al. BBT-877, a potent autotaxin inhibitor in clinical development to treat idiopathic pulmonary fibrosis. Eur Respir J. 2019;54:PA1293.
   Web of Science ®Google Scholar
• Mody D, Yu W, Lin J, et al. Clinical evaluation of cudetaxestat for safety,Tolerability, pharmacokinetics, pharmacodynamics, and potential drug-drug interactions. Am Thorac Soc Int Conf Meet Abstr. 2022;A2438–A2438. doi: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2438
   Google Scholar
• Yang L, Shu P, Wu N, et al. Pharmacokinetics, pharmacodynamics, safety and tolerability of FTP-198, a novel, selective autotaxin inhibitor, in healthy subjects: a phase I randomized placebo-controlled trial. Eur J Pharm Sci. 2023;189:189. doi: 10.1016/j.ejps.2023.106552
   Web of Science ®Google Scholar
• Armani E, Rizzi A, Iotti N, et al. Discovery of a potent, selective, and orally bioavailable tool compound for probing the role of lysophosphatidic acid type 2 receptor antagonists in fibrotic disorders. J Med Chem. 2023;66(8):5622–5656. doi: 10.1021/acs.jmedchem.2c02087
   PubMed Web of Science ®Google Scholar
• Palmer SM, Snyder L, Todd JL, et al. Randomized, double-blind, placebo-controlled, phase 2 trial of BMS-986020, a lysophosphatidic acid receptor antagonist for the treatment of idiopathic pulmonary fibrosis. Chest. 2018;154(5):1061–1069. doi: 10.1016/j.chest.2018.08.1058
   PubMed Web of Science ®Google Scholar
• Sivaraman L, Gill M, Nelson DM, et al. Structure dependence and species sensitivity of in vivo hepatobiliary toxicity with lysophosphatidic acid receptor 1 (LPA1) antagonists. Toxicol Appl Pharmacol. 2022;438:438. doi: 10.1016/j.taap.2021.115846
   Web of Science ®Google Scholar
• Cheng PTW, Kaltenbach RF, Zhang H, et al. Discovery of an oxycyclohexyl acid lysophosphatidic acid receptor 1 (LPA1) antagonist BMS-986278 for the treatment of pulmonary fibrotic diseases. J Med Chem. 2021;64(21):15549–15581. doi: 10.1021/acs.jmedchem.1c01256
   PubMed Web of Science ®Google Scholar
• Tirucherai GS, Yu D, Revankar R, et al. BMS-986278, a lysophosphatidic acid 1 (LPA 1) receptor antagonist, in healthy participants: a single/multiple ascending dose (SAD/MAD) and Japanese MAD (JMAD) phase 1 study. 2020; A1492–A1492.
   Google Scholar
• Gill MW, Murphy BJ, Cheng PTW, et al. Mechanism of hepatobiliary toxicity of the LPA1 antagonist BMS-986020 developed to treat idiopathic pulmonary fibrosis: contrasts with BMS-986234 and BMS-986278. Toxicol Appl Pharmacol. 2022;438:438. doi: 10.1016/j.taap.2022.115885
   Web of Science ®Google Scholar
• Corte TJ, Lancaster L, Swigris JJ, et al. Phase 2 trial design of BMS-986278, a lysophosphatidic acid receptor 1 (LPA1) antagonist, in patients with idiopathic pulmonary fibrosis (IPF) or progressive fibrotic interstitial lung disease (PF-ILD). BMJ Open Respir Res. 2021;8(1):e001026. doi: 10.1136/bmjresp-2021-001026
   PubMed Web of Science ®Google Scholar
• Corte TJ, Cottin V, Glassberg MK, et al. BMS-986278, an oral lysophosphatidic acid receptor 1 (LPA1) antagonist, for patients with idiopathic pulmonary fibrosis: results from a phase 2 randomized trial. 2023; A2785–A2785.
   Google Scholar