Back to Search
Start Over
Small Molecule Pin1 Inhibitor Blocking NF-κB Signaling in Prostate Cancer Cells.
- Source :
-
Chemistry, an Asian journal [Chem Asian J] 2018 Feb 02; Vol. 13 (3), pp. 275-279. Date of Electronic Publication: 2018 Jan 15. - Publication Year :
- 2018
-
Abstract
- Prolyl-isomerase 1 (Pin1) is a conserved enzyme that regulates cell processes such as cell cycle progression, transcriptional regulation, and apoptosis. However, overexpression of Pin1 is correlated with a higher probability of prostate tumor recurrence. We utilized a molecular docking technique to identify Pin1 inhibitors from a database of natural product and natural product-like compounds. The action of the hit compounds against Pin1 activity was studied using multiple methods, including a fluorometric enzymatic assay, co-immunoprecipitation, western blotting, cell thermal shiftm, and other techniques. We have identified compound 1 as a natural-product-like inhibitor of Pin1 activity via structure-based virtual screening and showed that compound 1 could target Pin1 and disrupt the interaction between Pin1 and the p65 subunit of NF-κB in cells. Furthermore, compound 1 reduced nuclear p65 (Thr254) phosphorylation and attenuated NF-κB activity in cells. Finally, compound 1 induced apoptosis in prostate cancer cells. Compound 1 represents a natural product-like Pin1 inhibitor that acts via targeting the Pin1-NF-κB interaction.<br /> (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Subjects :
- Cell Line
Enzyme Inhibitors chemistry
Humans
Male
Models, Molecular
Molecular Structure
NF-kappa B metabolism
NIMA-Interacting Peptidylprolyl Isomerase metabolism
Prostatic Neoplasms drug therapy
Prostatic Neoplasms genetics
Small Molecule Libraries chemistry
Enzyme Inhibitors pharmacology
NF-kappa B antagonists & inhibitors
NIMA-Interacting Peptidylprolyl Isomerase antagonists & inhibitors
Prostatic Neoplasms metabolism
Prostatic Neoplasms pathology
Signal Transduction drug effects
Small Molecule Libraries pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1861-471X
- Volume :
- 13
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Chemistry, an Asian journal
- Publication Type :
- Academic Journal
- Accession number :
- 29288531
- Full Text :
- https://doi.org/10.1002/asia.201701216