α4β7 integrin inhibitors: a patent review

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.