385
Views
2
CrossRef citations to date
0
Altmetric
Review

Targeting the LPA1 signaling pathway for fibrosis therapy: a patent review (2010-present)

, , , & ORCID Icon
Pages 1097-1122 | Received 05 Jan 2022, Accepted 27 Sep 2022, Published online: 14 Oct 2022
 

ABSTRACT

Introduction

Fibrosis is a disease that damages organs and even causes death. Because of the complicated pathogenesis, the development of drugs for fibrosis is challenging. In the lysophosphatidic acid receptor type 1 (LPA1) signaling pathway, LPA1 and its downstream Rho-associated coiled-coil forming protein kinase (ROCK) are related to the process of fibrosis. Targeting LPA1 signaling pathway is a potential strategy for the treatment of fibrosis.

Area covered

This review describes the process of fibrosis mediated by the LPA1 signaling pathway and then summarizes LPA1 antagonist patents reported since 2010 and ROCK inhibitor patents since 2017 according to their scaffolds based on the Cortellis Drug Discovery Intelligence database. Information on LPA1 antagonists entering clinical trials is integrated.

Expert opinion

Over the past decade, a large number of antagonists targeting the LPA1 signaling pathway have been patented for fibrosis therapy. A limited number of compounds have entered clinical trials. Different companies and research groups have used different scaffolds when designing compounds for fibrosis therapy. Therefore, LPA1 and ROCK are competitive targets for the development of new therapies for fibrosis to provide a potential treatment method for fibrosis in the future.

Article highlights

  • LPA1 is expressed at high levels in the process of fibrosis, and the degree of fibrosis may be alleviated by knocking out or antagonizing LPA1.

  • The LPA1 signaling pathway is closely related to the process of fibrosis. Antagonists of LPA1 with various scaffolds exert antifibrotic effects.

  • ROCK downstream of LPA1 causes cytoskeletal reorganization, regulates downstream fibrosis-related targets, such as CTGF, MMP and NF-κB, and then affects the process of fibrosis. Therefore, inhibitors targeting ROCK also treat fibrosis.

  • Patents disclose LPA1 antagonists and ROCK inhibitors. Some leads have also entered clinical trials.

  • Due to the wide distribution of LPA1 and ROCK, off-target effects cause adverse reactions. Drug structures were modified to reduce adverse reactions and improve physical and chemical properties.

This box summarizes key points contained in the article.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study was supported by Projects 81903439 of the National Natural Science Foundation of China, the Natural Science Foundation of Jiangsu Province of China (no. BK20190562).

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 99.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 1,757.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.