Targeting the TGF-β signaling pathway: an updated patent review (2021–present)

ABSTRACT

Introduction

The TGF-β signaling pathway is a complex network that plays a crucial role in regulating essential biological functions and is implicated in the onset and progression of multiple diseases. This review highlights the recent advancements in developing inhibitors targeting the TGF-β signaling pathway and their potential therapeutic applications in various diseases.

Area covered

The review discusses patents on active molecules related to the TGF-β signaling pathway, focusing on three strategies: TGF-β activity inhibition, blocking TGF-β receptor binding, and disruption of the signaling pathway using small molecule inhibitors. Combination therapies and the development of fusion proteins targeting multiple pathways are also explored. The literature search was conducted using the Cortellis Drug Discovery Intelligence database, covering patents from 2021 onwards.

Expert opinion

The development of drugs targeting the TGF-β signaling pathway has made significant progress in recent years. However, addressing challenges such as specificity, systemic toxicity, and patient selection is crucial for their successful clinical application. Targeting the TGF-β signaling pathway holds promise as a promising approach for the treatment of various diseases.

KEYWORDS:

• TGF-β signaling pathway
• antitumor agents
• antifibrotic agents
• patent review
• clinical application

Article highlights

• The importance of the TGF-β signaling pathway in regulating various biological processes, including diseases such as cancer, fibrosis, and autoimmune diseases.

• The activation of TGF-β is a complex process involving the participation of various factors, such as integrins, LTBPs, and GARP. The development of drugs targeting the activation of TGF-β has broad prospects for research.

• TGF-β antibodies, TGF-β ligand traps, and inhibitors of TGF-β receptor kinases have shown potential to inhibit TGF-β signaling. Additionally, combination therapies and the development of fusion proteins targeting multiple pathways may enhance therapeutic efficacy.

• Targets of both the Smad-dependent and Smad-independent signaling pathways of TGF-β have been well studied. Several active molecules are currently enrolled in clinical trials, which may compensate for the safety defects of direct TGF-β antagonists.

• The review aims to provide insights into the development of TGF-β inhibitors by discussing the various strategies mentioned above.

Declaration of interest

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

A peer reviewer on this manuscript has received an honorarium for their review work. Peer reviewers on this manuscript have no other 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.