Outline of gelatinase inhibitors as anti-cancer agents: A patent mini-review for 2010-present

Eur J Med Chem. 2021 Mar 5:213:113044. doi: 10.1016/j.ejmech.2020.113044. Epub 2020 Nov 24.

Abstract

Matrix metalloproteinases (MMPs) are involved in several pathological and physiological functions. Gelatinases (MMP-2 and -9) have significant attention as therapeutic targets against cancer. Gelatinase inhibitors have demonstrated their effectiveness in several diseases including cancer. However, it is quite a challenging task to develop inhibitors as a therapeutic agent. This review summarizes the patent dedicated to the medicinal chemistry of gelatinase inhibitor reported over last decades. We examine the patent being pursued for gelatinase inhibitor development to highlight the key issues. The main aim is to provide the scientific community with an overview of the patented gelatinase inhibitors to allow further development. During early 2000s, some MMP inhibitors failed to pass the clinical trials. Hence, the lessons learned from early evidence and recent knowledge in that field will rejuvenate the development of selective inhibitors. Various studies and patents have continued in the recent years to expand knowledge. Continuously, our research team has been involved in the design of potent and selective gelatinase inhibitors for the past few years. This study is a part of our efforts. This study may be beneficial in the design and development of better gelatinase inhibitors in the future.

Keywords: Cancer; Gelatinase inhibitor; Hydroxamate; Matrix metalloproteinase; Medicinal chemistry.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Biphenyl Compounds / pharmacology
  • Diphosphonates / pharmacology
  • Drug Design
  • Humans
  • Hydroxamic Acids / chemistry*
  • Hydroxamic Acids / pharmacology
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / metabolism*
  • Matrix Metalloproteinase Inhibitors / chemistry*
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • Models, Molecular
  • Organic Chemicals / pharmacology
  • Phenylbutyrates / pharmacology
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Biphenyl Compounds
  • Diphosphonates
  • Hydroxamic Acids
  • Matrix Metalloproteinase Inhibitors
  • Organic Chemicals
  • Phenylbutyrates
  • prinomastat
  • Bay 12-9566
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9