Periaatteesa ADAM17 inhibiittori joko estää ADAM17 sheddaasi finktiota, voisi vähentää esim EBOV indfektiossa EBOV- gp aprtikkeleiden shed muotoa joka kylväytyy. Intestianalsita ADAM17 inhiboi tai ainakin vähentää MUC1- sheddaasi-funktiosta alkoholi, jolla on lääkemerkitystä.
Kuva TACE- funktiosta , millä EBOV gp kylväytyy: Tästä aiheuttaa tavaton sytokiinimyrsky. TACE sinänsä muistuttaa käärmeen myrkyn disintegriiniä, jonka tehtävä on liudentaa uhri nielemiskuntoon.
Curr Drug Targets. 2016;17(16):1908-1927.
Targeting ADAM17 Sheddase Activity in Cancer.
Abstract
A
disintegrin and metalloprotease (ADAM)17 is a sheddase, capable of
releasing the ectodomains of membrane proteins such as growth factors
(e.g. Epidermal Growth Factor Receptor ligands), cytokines and their
receptors, adhesion and signaling molecules. These activities regulate
several physiological and pathological processes including inflammation,
tumor growth and metastatic progression. In this review, we will
summarize ADAM17 biology and focus on its role in cancer and the
possible usage of ADAM17 inhibitors in cancer therapy. Recent achievements in this area include the development of small molecule metalloprotease inhibitors
with enhanced specificity for ADAM17, monoclonal antibodies, and
synthetic short RNA molecules for gene silencing. These approaches
successfully inhibited cancer cell growth and invasiveness or sensitized
them to cytotoxic drugs, ionizing radiations or targeted therapies, in
preclinical studies. These findings suggest the repositioning of ADAM17 inhibitors,
which have yet proven unsuccessful as anti-inflammatory agents, for the
development of new anti-cancer therapies, particularly in EGFR
ligand-dependent cancers. Future studies should address ADAM17 inhibitors as short-term treatments in combination with different anti-cancer therapies.
- PMID:
- 27469341
- [Indexed for MEDLINE]
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