Insulin-Degrading Enzyme Is a Non Proteasomal Target of Carfilzomib and Affects the 20S Proteasome Inhibition by the Drug.


Journal

Biomolecules
ISSN: 2218-273X
Titre abrégé: Biomolecules
Pays: Switzerland
ID NLM: 101596414

Informations de publication

Date de publication:
16 02 2022
Historique:
received: 10 08 2021
revised: 12 01 2022
accepted: 27 01 2022
entrez: 25 2 2022
pubmed: 26 2 2022
medline: 9 4 2022
Statut: epublish

Résumé

Carfilzomib is a last generation proteasome inhibitor (PI) with proven clinical efficacy in the treatment of relapsed/refractory multiple myeloma. This drug is considered to be extremely specific in inhibiting the chymotrypsin-like activity of the 20S proteasome, encoded by the β5 subunit, overcoming some bortezomib limitations, the first PI approved for multiple myeloma therapy which is however burdened by a significant toxicity profile, due also to its off-target effects. Here, molecular approaches coupled with molecular docking studies have been used to unveil that the Insulin-Degrading Enzyme, a ubiquitous and highly conserved Zn

Identifiants

pubmed: 35204815
pii: biom12020315
doi: 10.3390/biom12020315
pmc: PMC8869475
pii:
doi:

Substances chimiques

Antineoplastic Agents 0
Oligopeptides 0
Pharmaceutical Preparations 0
Proteasome Inhibitors 0
carfilzomib 72X6E3J5AR
Insulysin EC 3.4.24.56
Proteasome Endopeptidase Complex EC 3.4.25.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

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Auteurs

Grazia Raffaella Tundo (GR)

IRCCS-Fondazione BIETTI, 00198 Rome, Italy.

Diego Sbardella (D)

IRCCS-Fondazione BIETTI, 00198 Rome, Italy.

Francesco Oddone (F)

IRCCS-Fondazione BIETTI, 00198 Rome, Italy.

Giuseppe Grasso (G)

Department of Chemical Science, University of Catania, 95125 Catania, Italy.

Stefano Marini (S)

Department of Clinical Sciences and Translational Medicine, University of Roma Tor Vergata, 00133 Rome, Italy.

Maria Grazia Atzori (MG)

Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.

Anna Maria Santoro (AM)

Institute of Crystallography, CNR, 95126 Catania, Italy.

Danilo Milardi (D)

Institute of Crystallography, CNR, 95126 Catania, Italy.

Francesco Bellia (F)

Institute of Crystallography, CNR, 95126 Catania, Italy.

Gabriele Macari (G)

Department of Sciences, Rome Tre University, 00146 Rome, Italy.

Grazia Graziani (G)

Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy.

Fabio Polticelli (F)

Department of Sciences, Rome Tre University, 00146 Rome, Italy.
National Institute of Nuclear Physics, Rome Tre Section, 00146 Rome, Italy.

Paolo Cascio (P)

Department of Veterinary Sciences, University of Turin, 10095 Grugliasco, Italy.

Mariacristina Parravano (M)

IRCCS-Fondazione BIETTI, 00198 Rome, Italy.

Massimo Coletta (M)

IRCCS-Fondazione BIETTI, 00198 Rome, Italy.

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Classifications MeSH