Detailed Information

Cited 0 time in webofscience Cited 0 time in scopus
Metadata Downloads

Identification of the Antidepressant Vilazodone as an Inhibitor of Inositol Polyphosphate Multikinase by Structure-Based Drug Repositioning

Authors
Lee, BoahPark, Seung JuLee, SeulgiPark, Seung EunLee, EunhyeSong, Ji-JoonByun, YoungjooKim, Seyun
Issue Date
3월-2020
Publisher
KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
Keywords
drug repositioning; inositol phosphate; IPMK; vilazodone; virtual screening
Citation
MOLECULES AND CELLS, v.43, no.3, pp.222 - 227
Indexed
SCIE
SCOPUS
KCI
Journal Title
MOLECULES AND CELLS
Volume
43
Number
3
Start Page
222
End Page
227
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/57487
DOI
10.14348/molcells.2020.0051
ISSN
1016-8478
Abstract
Inositol polyphosphate multikinase (IPMK) is required for the biosynthesis of inositol phosphates (IPs) through the phosphorylation of multiple IP metabolites such as IP3 and IP4. The biological significance of IPMK's catalytic actions to regulate cellular signaling events such as growth and metabolism has been studied extensively. However, pharmacological reagents that inhibit IPMK have not yet been identified. We employed a structure-based virtual screening of publicly available U.S. Food and Drug Administration-approved drugs and chemicals that identified the antidepressant, vilazodone, as an IPMK inhibitor. Docking simulations and pharmacophore analyses showed that vilazodone has a higher affinity for the ATP-binding catalytic region of IPMK than ATP and we validated that vilazodone inhibits IPMK's IP kinase activities in vitro. The incubation of vilazodone with NIH3T3-L1 fibroblasts reduced cellular levels of IP5 and other highly phosphorylated IPs without influencing IP4 levels. We further found decreased Akt phosphorylation in vilazodone-treated HCT116 cancer cells. These data clearly indicate selective cellular actions of vilazodone against IPMK-dependent catalytic steps in IP metabolism and Akt activation. Collectively, our data demonstrate vilazodone as a method to inhibit cellular IPMK, providing a valuable pharmacological agent to study and target the biological and pathological processes governed by IPMK.
Files in This Item
There are no files associated with this item.
Appears in
Collections
College of Pharmacy > Department of Pharmaceutical Science > 1. Journal Articles

qrcode

Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Researcher Byun, Young joo photo

Byun, Young joo
약학대학 (약학과)
Read more

Altmetrics

Total Views & Downloads

BROWSE