Monoclonal antibodies against metzincin targets

British Journal of Pharmacology
Salvatore Santamaria, Rens de Groot

Abstract

The metzincin clan of metalloproteinases includes the MMP, disintegrin and metalloproteinase (ADAM) and ADAM with thrombospondin motifs families, which cleave extracellular targets in a wide range of (patho)physiological processes. Antibodies constitute a powerful tool to modulate the activity of these enzymes for both therapeutic and research purposes. In this review, we give an overview of monoclonal antibodies (mAbs) that have been tested in preclinical disease models, human trials and important studies of metzincin structure and function. Initial attempts to develop therapeutic small molecule inhibitors against MMPs were hampered by structural similarities between metzincin active sites and, consequently, off-target effects. Therefore, more recently, mAbs have been developed that do not bind to the active site but bind to surface-exposed loops that are poorly conserved in closely related family members. Inhibition of protease activity by these mAbs occurs through a variety of mechanisms, including (i) barring access to the active site, (ii) disruption of exosite binding, and (iii) prevention of protease activation. These different modes of inhibition are discussed in the context of the antibodies' potency, selectivity and, ...Continue Reading

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Citations

Jan 19, 2020·The Journal of Biological Chemistry·Amir S RazaiGuy S Salvesen
Dec 5, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anna M KnapinskaGregg B Fields
Dec 14, 2018·British Journal of Pharmacology·James R WhitefordGiulia De Rossi
May 30, 2019·Pharmaceuticals·Anna M Knapinska, Gregg B Fields
Mar 29, 2020·International Journal of Experimental Pathology·Salvatore Santamaria
Jul 31, 2019·Scientific Reports·Salvatore SantamariaJosefin Ahnström
Sep 10, 2020·MedChemComm·Geetha B KumarDavid B C Martin
Dec 23, 2020·Open Biology·Salvatore Santamaria, Rens de Groot
Jan 15, 2021·Scientific Reports·Salvatore SantamariaJosefin Ahnström
Apr 4, 2021·International Journal of Molecular Sciences·Preston CareyM Sharon Stack
Apr 4, 2021·International Journal of Molecular Sciences·Tania FontanilSantiago Cal
Jun 29, 2021·Circulation Research·Taiji MizoguchiPatrick T Ellinor
Aug 10, 2021·Frontiers in Molecular Biosciences·Stefano PludaAlessandro Angelini
May 28, 2020·Journal of Medicinal Chemistry·Pauline ZipfelPatrick Dallemagne
Aug 27, 2021·Frontiers in Molecular Biosciences·Lejian JiangMao Lin

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