Strategies to Target ADAM17 in Disease: From Its Discovery to the IRhom Revolution

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2021 Feb 13

PMID 33579029

Citations 51

Authors

Matteo Calligaris

Doretta Cuffaro

Simone Bonelli

Donatella Pia Spano

Armando Rossello

Elisa Nuti

Simone Dario Scilabra

Affiliations

Soon will be listed here.

Abstract

For decades, disintegrin and metalloproteinase 17 (ADAM17) has been the object of deep investigation. Since its discovery as the tumor necrosis factor convertase, it has been considered a major drug target, especially in the context of inflammatory diseases and cancer. Nevertheless, the development of drugs targeting ADAM17 has been harder than expected. This has generally been due to its multifunctionality, with over 80 different transmembrane proteins other than tumor necrosis factor α (TNF) being released by ADAM17, and its structural similarity to other metalloproteinases. This review provides an overview of the different roles of ADAM17 in disease and the effects of its ablation in a number of in vivo models of pathological conditions. Furthermore, here, we comprehensively encompass the approaches that have been developed to accomplish ADAM17 selective inhibition, from the newest non-zinc-binding ADAM17 synthetic inhibitors to the exploitation of iRhom2 to specifically target ADAM17 in immune cells.

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