Gelatinase inhibitors: a patent review (2011-2017)

ABSTRACT

Introduction: Gelatinase represents a promising biotarget in new drug development as it is closely related to various pathological events, including but not limited to neoplasm, aging, respiratory and neurological disorders. Gelatinase inhibitors are thereby designated as chemotherapeutics or as mechanistic probe to figure out the unrecognized functions of MMP members.

Areas covered: The focus of this article is to highlight recently issued patents concerning the naturally available or synthetic gelatinase inhibitors (2011–2017), where the chemical structures, SAR investigation, biological application. Besides, the binding modes of representative inhibitors with gelatinase are also briefly described.

Expert opinion: The access of crystallographic structure of inhibitor complexed with gelatinase, the availability of pharmacophoric features of gelatinase inhibitors, together with the proper use of drug design protocols, have paved the way for developing more selective and potent modulators. Moreover, considering typical bio-assessment was primarily concentrated on the antitumor effect, the other bioactivity outcomes should also be concerned to look for new application of gelatinase inhibitors.

KEYWORDS:

• MMP
• gelatinase inhibitor
• isoform selectivity
• binding mode
• drug design strategy

Article highlights

• This article covers recently issued patents on gelatinase inhibitors, including synthetic and naturally available compounds.

• Chemical structures, biological activity, and binding patterns of representative inhibitors with gelatinase are summarized in detail.

• The deep understanding the crystallographic structure of inhibitor complexed with gelatinase enables further structure-based design of new inhibitors for selectivity purpose.

• The possible strategies to achieve novel gelatinase inhibitors with more potent and high selectivity are comprehensively discussed.

This box summarizes key points contained in this article.

Declaration of interest

The authors have no other 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 apart from those disclosed.

Additional information

Funding

The paper received financial support from the Science and Technology Major Projects of Shandong Province (No 2016GSF201175 to X. Li; No. 2015ZDJS04001 to F.S. Wang), and also the Rolling program of ‘ChangJiang Scholars and Innovative Research Team in University’ (No. IRT_17R68 to Y.M. Shen)