Third generation of matrix metalloprotease inhibitors: Gain in selectivity by targeting the depth of the S1′ cavity

Devel, Laurent; Czarny, Bertrand; Beau, Fabrice; Georgiadis, Dimitris; Stura, E.A.; Dive, Vincent

doi:10.1016/j.biochi.2010.07.017

Cited by 78 publications

(69 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…One such strategy focused on designing smallmolecule inhibitors that fit in size and shape with the variable S1′ deep cavity of the catalytic domain as an alternative approach to disrupting the strong catalytic zinc-binding activity using MMP12-inhibition models. 147,148 Pseudopeptides with the general formula X-l-Glu-NH 2 that affected zinc ion binding were recognized as MMP12 inhibitors. 149 More recently, two monoclonal antibodies have been designed to inhibit substrate activation by binding to the catalytic domain without affecting the catalytic zinc region.…”

mentioning

confidence: 99%

Matrix metalloproteinases in head and neck cancer: current perspectives

Gkouveris¹,

Nikitakis²,

Aseervatham³

et al. 2017

MNM

View full text Add to dashboard Cite

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases encoded by 24 distinct genes. Their functions have been implicated in numerous normal and pathologic processes, including uterine involution and organogenesis, inflammation and wound healing, vascular and autoimmune disease progression. Pertinent to this review, the role of MMPs in cancer biology is fairly well researched and documented, and remains a subject of continuing intense investigation. Not only are several MMPs overexpressed in head and neck squamous cell carcinomas (HNSCCs), expression has been correlated with salient tumorigenic hallmarks, such as cell proliferation, angiogenesis, invasion, and metastasis. The utility of changes in the expression profile, as well as various MMP polymorphisms as potential prognostic markers in oral cancers and oral premalignant lesions, have been investigated. Furthermore, the potential therapeutic utility of targeting MMPs in cancer remains attractive, although outcomes in this respect appear so far to be less encouraging with respect to HNSCCs. Because of the disappointing results observed in clinical trials where MMP-targeting regimens for HNSCCs utilized broad-spectrum small MMP catalytic site inhibitors, investigators now envision new strategies for MMP-specific targeting based on the recognition of new noncatalytic MMP domains with distinct functions. This review provides an overview of MMP activities in general and in cancers, and an update of their activities in HNSCC. Specifically, their role in the development and progression of HNSCC and their function as signaling molecules is discussed. Finally, their role as potential prognostic biomarkers and therapeutic targets in HNSCC is revisited.

show abstract

mentioning

confidence: 99%

Matrix metalloproteinases in head and neck cancer: current perspectives

Gkouveris¹,

Nikitakis²,

Aseervatham³

et al. 2017

MNM

View full text Add to dashboard Cite

show abstract

“…Because MMPs have not only disease promoting but also inhibiting functions (53, 54), a major challenge in current MMP inhibitor design is selectivity toward target MMPs (55,56). Our refined specificity profile discriminates MMP10 e.g.…”

Section: Discussionmentioning

confidence: 99%