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Review

α4β7 integrin inhibitors: a patent review

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Pages 903-917 | Received 30 Jul 2018, Accepted 13 Nov 2018, Published online: 22 Nov 2018
 

ABSTRACT

Introduction: The α4β7 integrin is heterodimeric cell surface receptors expressed on most leukocytes. Mucosal addressing cell adhesion molecule 1(MAdCAM-1) is an exclusive ligand for α4β7 integrin.

Areas covered: This article will highlight the progress that has been made in the discovery and development of α4β7 integrin inhibitors, and their use in the treatment of inflammatory bowel diseases, multiple sclerosis, asthma, hepatic disorders, human immunodeficiency virus, allergic conjunctivitis and type 1 diabetes.

Expert opinion: α4β7 integrin inhibitors have attracted much interest for their clinical implication. Natalizumab and Vedolizumab are monoclonal antibodies (mAbs) successfully utilized clinically. Natalizumab is a mAbs of α4-subunit blocking both α4β1 and α4β7 integrin. Vedolizumab selectively targets the α4β7 integrin. Several mAbs are still in the process of research and development. Among these mAbs, etrolizumab selectively against the β7-subunit and AMG-181 specifically against the α4β7 integrin are the most promising anti-α4β7 integrin antibodies. Despite the unclear development stage of TR-14035 and R411, several low molecular compounds show bright future of further development, such as AJM300 and CDP323. In addition, results from laboratory data show that peptide inhibitors, such as peptide X, are effective α4β7 integrin inhibitors.

Article highlights

  • α4β7 integrin inhibitors can be used in the treatment of inflammatory bowel diseases (IBD), multiple sclerosis (MS), asthma, hepatic disorders, human immunodeficiency virus (HIV), allergic conjunctivitis, and type 1 diabetes.

  • Etrolizumab and AMG-181 are the most promising anti-α4β7 integrin antibodies.

  • Low molecular compounds of α4β7 integrin inhibitors still have a very attractive prospect, such as AJM300 and CDP323.

  • Peptide X is a potent effective α4β7 integrin inhibitor.

This box summarizes key points contained in the article.

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

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

Additional information

Funding

This project was sponsored by the grants from National Major Scientific, Technological Special Project for ‘Significant New Drugs Development’ [2011ZX09302-003-02]; the Fundamental Research Funds for the Central Universities [17JCYB11].

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