Design and Development of Autotaxin Inhibitors

Autotaxin (ATX) is the only enzyme of the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP2) family with lysophospholipase D (lysoPLD) activity, which is mainly responsible for the hydrolysis of extracellular lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA). LPA can induce vario...

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Autores principales:	Yi Jia, Yan Li, Xu-Dong Xu, Yu Tian, Hai Shang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	autotaxin inhibitor lysophosphatidic acid structure design development Medicine R Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/e38a230d4a6e432db33b44876d801431
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spelling	oai:doaj.org-article:e38a230d4a6e432db33b44876d8014312021-11-25T18:40:12ZDesign and Development of Autotaxin Inhibitors10.3390/ph141112031424-8247https://doaj.org/article/e38a230d4a6e432db33b44876d8014312021-11-01T00:00:00Zhttps://www.mdpi.com/1424-8247/14/11/1203https://doaj.org/toc/1424-8247Autotaxin (ATX) is the only enzyme of the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP2) family with lysophospholipase D (lysoPLD) activity, which is mainly responsible for the hydrolysis of extracellular lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA). LPA can induce various responses, such as cell proliferation, migration, and cytokine production, through six G protein-coupled receptors (LPA1-6). This signaling pathway is associated with metabolic and inflammatory disorder, and inhibiting this pathway has a positive effect on the treatment of related diseases, while ATX, as an important role in the production of LPA, has been shown to be associated with the occurrence and metastasis of tumors, fibrosis and cardiovascular diseases. From mimics of ATX natural lipid substrates to the rational design of small molecule inhibitors, ATX inhibitors have made rapid progress in structural diversity and design over the past 20 years, and three drugs, GLPG1690, BBT-877, and BLD-0409, have entered clinical trials. In this paper, we will review the structure of ATX inhibitors from the perspective of the transformation of design ideas, discuss the advantages and disadvantages of each inhibitor type, and put forward prospects for the development of ATX inhibitors in the future.Yi JiaYan LiXu-Dong XuYu TianHai ShangMDPI AGarticleautotaxininhibitorlysophosphatidic acidstructure designdevelopmentMedicineRPharmacy and materia medicaRS1-441ENPharmaceuticals, Vol 14, Iss 1203, p 1203 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	autotaxin inhibitor lysophosphatidic acid structure design development Medicine R Pharmacy and materia medica RS1-441
spellingShingle	autotaxin inhibitor lysophosphatidic acid structure design development Medicine R Pharmacy and materia medica RS1-441 Yi Jia Yan Li Xu-Dong Xu Yu Tian Hai Shang Design and Development of Autotaxin Inhibitors
description	Autotaxin (ATX) is the only enzyme of the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP2) family with lysophospholipase D (lysoPLD) activity, which is mainly responsible for the hydrolysis of extracellular lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA). LPA can induce various responses, such as cell proliferation, migration, and cytokine production, through six G protein-coupled receptors (LPA1-6). This signaling pathway is associated with metabolic and inflammatory disorder, and inhibiting this pathway has a positive effect on the treatment of related diseases, while ATX, as an important role in the production of LPA, has been shown to be associated with the occurrence and metastasis of tumors, fibrosis and cardiovascular diseases. From mimics of ATX natural lipid substrates to the rational design of small molecule inhibitors, ATX inhibitors have made rapid progress in structural diversity and design over the past 20 years, and three drugs, GLPG1690, BBT-877, and BLD-0409, have entered clinical trials. In this paper, we will review the structure of ATX inhibitors from the perspective of the transformation of design ideas, discuss the advantages and disadvantages of each inhibitor type, and put forward prospects for the development of ATX inhibitors in the future.
format	article
author	Yi Jia Yan Li Xu-Dong Xu Yu Tian Hai Shang
author_facet	Yi Jia Yan Li Xu-Dong Xu Yu Tian Hai Shang
author_sort	Yi Jia
title	Design and Development of Autotaxin Inhibitors
title_short	Design and Development of Autotaxin Inhibitors
title_full	Design and Development of Autotaxin Inhibitors
title_fullStr	Design and Development of Autotaxin Inhibitors
title_full_unstemmed	Design and Development of Autotaxin Inhibitors
title_sort	design and development of autotaxin inhibitors
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e38a230d4a6e432db33b44876d801431
work_keys_str_mv	AT yijia designanddevelopmentofautotaxininhibitors AT yanli designanddevelopmentofautotaxininhibitors AT xudongxu designanddevelopmentofautotaxininhibitors AT yutian designanddevelopmentofautotaxininhibitors AT haishang designanddevelopmentofautotaxininhibitors
_version_	1718410868175142912

Design and Development of Autotaxin Inhibitors

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