Recent research advances in ATX inhibitors: An overview of primary literature

Zhang, Cheng; Liu, Yue; Zhou, Qing; Fan, Hongze; Liu, Huan; Hu, Jinxing

doi:10.1016/j.bmc.2023.117374

Cited by 7 publications

(6 citation statements)

References 52 publications

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“…ATX substrate binding-pocket targeting inhibitors are currently divided into five different classes [ 83 ]. Class I are lipid-like or orthosteric inhibitors, with the early inhibitor PF-8380 being the prototypical inhibitor of this class [ 84 , 85 ].…”

Section: Summary Of the Current State Of Lpa Pathway Pharmacological ...mentioning

confidence: 99%

“…More modern inhibitors are non-carboxylic and non-lipid in design [ 86 ]. Class II inhibitors target the hydrophobic pocket (including GRI-918013, none of which are in trials), obstructing binding of LPC to ATX [ 83 ]. Class III inhibitors are allosteric tunnel inhibitors, which act non-competitively to deter the release and transport of hydrolyzed LPA, which includes the inhibitor PAT-347 by PharaAkea Inc. [ 87 ].…”

Section: Summary Of the Current State Of Lpa Pathway Pharmacological ...mentioning

confidence: 99%

“…Class III inhibitors are allosteric tunnel inhibitors, which act non-competitively to deter the release and transport of hydrolyzed LPA, which includes the inhibitor PAT-347 by PharaAkea Inc. [ 87 ]. Class IV inhibitors, described as pocket-tunnel hybrids, include ziritaxestat, and essentially represent inhibitors with combined features of both class II and III inhibitors [ 83 ]. Finally, steroid-derived hybrids which function as both orthosteric and allosteric inhibitors that do not form interactions with the catalytic sites have recently been described and represent the latest class (class V) to be proposed [ 88 ].…”

Section: Summary Of the Current State Of Lpa Pathway Pharmacological ...mentioning

confidence: 99%

“…In general, the most potent ATX inhibitors belong to classes II, III, IV, given how closely they interact or block access to the zinc ion-containing active site [86]. The history of ATX inhibition design has been summarized in several good reviews [83,[89][90][91][92][93].…”

Section: Summary Of the Current State Of Lpa Pathway Pharmacological ...mentioning

confidence: 99%

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Autotaxin and Lysophosphatidate Signaling: Prime Targets for Mitigating Therapy Resistance in Breast Cancer

Benesch,

Tang,

Brindley

et al. 2024

World J Oncol

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Overcoming and preventing cancer therapy resistance is the most pressing challenge in modern breast cancer management. Consequently, most modern breast cancer research is aimed at understanding and blocking these therapy resistance mechanisms. One increasingly promising therapeutic target is the autotaxin (ATX)-lysophosphatidate (LPA)-lipid phosphate phosphatase (LPP) axis. Extracellular LPA, produced from albumin-bound lysophosphatidylcholine by ATX and degraded by the ecto-activity of the LPPs, is a potent cell-signaling mediator of tumor growth, invasion, angiogenesis, immune evasion, and resistance to cancer treatment modalities. LPA signaling in the post-natal organism has central roles in physiological wound healing, but these mechanisms are subverted to fuel pathogenesis in diseases that arise from chronic inflammatory processes, including cancer. Over the last 10 years, our understanding of the role of LPA signaling in the breast tumor microenvironment has begun to mature. Tumor-promoting inflammation in breast cancer leads to increased ATX production within the tumor microenvironment. This results in increased local concentrations of LPA that are maintained in part by decreased overall cancer cell LPP expression that would otherwise more rapidly break it down. LPA signaling through six G-protein-coupled LPA receptors expressed by cancer cells can then activate virtually every known tumorigenic pathway. Consequently, to target therapy resistance and tumor growth mediated by LPA signaling, multiple inhibitors against the LPA signaling axis are entering clinical trials. In this review, we summarize recent developments in LPA breast cancer biology, and illustrate how these novel therapeutics against the LPA signaling pathway may be excellent adjuncts to extend the efficacy of evolving breast cancer treatments.

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Section: Summary Of the Current State Of Lpa Pathway Pharmacological ...mentioning

confidence: 99%

Section: Summary Of the Current State Of Lpa Pathway Pharmacological ...mentioning

confidence: 99%

Section: Summary Of the Current State Of Lpa Pathway Pharmacological ...mentioning

confidence: 99%

Section: Summary Of the Current State Of Lpa Pathway Pharmacological ...mentioning

confidence: 99%

See 2 more Smart Citations

Autotaxin and Lysophosphatidate Signaling: Prime Targets for Mitigating Therapy Resistance in Breast Cancer

Benesch,

Tang,

Brindley

et al. 2024

World J Oncol

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“…Several compounds with inhibitory activity against ATX have been investigated in preclinical and clinical studies [90]. These inhibitors can be small molecules or biologics designed to disrupt the enzymatic activity of ATX or its interactions with its substrates [91]. cPA is also a physiological constituent of human serum [92].…”

Section: Overview Of Cyclic Phosphatidic Acidmentioning

confidence: 99%

A Review of Cyclic Phosphatidic Acid and Other Potential Therapeutic Targets for Treating Osteoarthritis

Tsukahara,

Imamura,

Morohoshi

2023

Biomedicines

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Osteoarthritis (OA), a chronic degenerative joint disease, is the most common form of arthritis. OA occurs when the protective cartilage that cushions the ends of bones gradually breaks down. This leads to the rubbing of bones against each other, resulting in pain and stiffness. Cyclic phosphatidic acid (cPA) shows promise as a treatment for OA. In this article, we review the most recent findings regarding the biological functions of cPA signaling in mammalian systems, specifically in relation to OA. cPA is a naturally occurring phospholipid mediator with unique cyclic phosphate rings at the sn-2 and sn-3 positions in the glycerol backbone. cPA promotes various responses, including cell proliferation, migration, and survival. cPA possesses physiological activities that are distinct from those elicited by lysophosphatidic acid; however, its biochemical origin has rarely been studied. Although there is currently no cure for OA, advances in medical research may lead to new therapies or strategies in the future, and cPA has potential therapeutic applications.

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Design, synthesis and evaluation of 3-(2-(substituted benzyloxy)benzylidene) pyrrolidine-2,5-dione derivatives for novel ATX inhibitor

Hyeong Lee,

Jin Park,

Young Lee

et al. 2024

Bioorganic & Medicinal Chemistry Letters

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Recent research advances in ATX inhibitors: An overview of primary literature

Cited by 7 publications

References 52 publications

Autotaxin and Lysophosphatidate Signaling: Prime Targets for Mitigating Therapy Resistance in Breast Cancer

Autotaxin and Lysophosphatidate Signaling: Prime Targets for Mitigating Therapy Resistance in Breast Cancer

A Review of Cyclic Phosphatidic Acid and Other Potential Therapeutic Targets for Treating Osteoarthritis

Design, synthesis and evaluation of 3-(2-(substituted benzyloxy)benzylidene) pyrrolidine-2,5-dione derivatives for novel ATX inhibitor

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