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RESEARCH PRODUCT
Strategies to Target ADAM17 in Disease: From Its Discovery to the iRhom Revolution
Elisa NutiDoretta CuffaroDonatella Pia SpanòArmando RosselloSimone BonelliSimone D. ScilabraMatteo Calligarissubject
TIMPsEGFRiRhomsTNFAnti-Inflammatory AgentsPharmaceutical ScienceInflammationContext (language use)Antineoplastic AgentsDiseaseComputational biologyReviewADAM17 ProteinmetalloproteinasesAnalytical Chemistrylcsh:QD241-44103 medical and health sciences0302 clinical medicineImmune systemlcsh:Organic chemistryIn vivoNeoplasmsDrug DiscoverymedicineDisintegrinTIMPADAM17 ProteinAnimalsHumansPhysical and Theoretical Chemistry030304 developmental biologyInflammation0303 health sciencesADAM17biologyOrganic ChemistryIntracellular Signaling Peptides and ProteinsiRhomChemistry (miscellaneous)030220 oncology & carcinogenesisbiology.proteinADAM17; Ectodomain shedding; EGFR; IRhoms; Metalloproteinases; TIMPs; TNF; ADAM17 Protein; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Humans; Inflammation; Intracellular Signaling Peptides and Proteins; NeoplasmsMolecular MedicineTumor necrosis factor alphametalloproteinaseectodomain sheddingmedicine.symptomdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-02-01 | Molecules |