Discovery of the Hedgehog Pathway Inhibitor Pipinib that Targets PI4KIIIß
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00511324" target="_blank" >RIV/61388963:_____/19:00511324 - isvavai.cz</a>
Result on the web
<a href="https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201907632" target="_blank" >https://onlinelibrary.wiley.com/doi/full/10.1002/anie.201907632</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/anie.201907632" target="_blank" >10.1002/anie.201907632</a>
Alternative languages
Result language
angličtina
Original language name
Discovery of the Hedgehog Pathway Inhibitor Pipinib that Targets PI4KIIIß
Original language description
The Hedgehog (Hh) signaling pathway is crucial for vertebrate embryonic development, tissue homeostasis and regeneration. Hh signaling is upregulated in basal cell carcinoma and medulloblastoma and Hh pathway inhibitors targeting the Smoothened (SMO) protein are in clinical use. However, the signaling cascade is incompletely understood and novel druggable proteins in the pathway are in high demand. We describe the discovery of the Hh‐pathway modulator Pipinib by means of cell‐based screening. Target identification and validation revealed that Pipinib selectively inhibits phosphatidylinositol 4‐kinase IIIβ (PI4KB) and suppresses GLI‐mediated transcription and Hh target gene expression by impairing SMO translocation to the cilium. Therefore, inhibition of PI4KB and, consequently, reduction in phosphatidyl‐4‐phosphate levels may be considered an alternative approach to inhibit SMO function and thus, Hedgehog signaling.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10401 - Organic chemistry
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Angewandte Chemie - International Edition
ISSN
1433-7851
e-ISSN
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Volume of the periodical
58
Issue of the periodical within the volume
46
Country of publishing house
DE - GERMANY
Number of pages
12
Pages from-to
16617-16628
UT code for WoS article
000493890600045
EID of the result in the Scopus database
2-s2.0-85074445164