Discovery of the Hedgehog Pathway Inhibitor Pipinib that Targets PI4KIIIß

to related objects

Abstract: 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.

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Bibliographic citation: Discovery of the Hedgehog Pathway Inhibitor Pipinib that Targets PI4KIIIß ; volume:131 ; number:46 ; year:2019 ; pages:16770-16781 ; extent:12
Angewandte Chemie ; 131, Heft 46 (2019), 16770-16781 (gesamt 12)

Creator: Kremer, Lea
Hennes, Elisabeth
Brause, Alexandra
Ursu, Andrei
Robke, Lucas
Matsubayashi, Hideaki T.
Nihongaki, Yuta
Flegel, Jana
Mejdrová, Ivana
Eickhoff, Jan
Baumann, Matthias
Nencka, Radim
Janning, Petra
Kordes, Susanne
Schöler, Hans R.
Sterneckert, Jared
Inoue, Takanari
Ziegler, Slava
Waldmann, Herbert

DOI: 10.1002/ange.201907632

URN: urn:nbn:de:101:1-2022070712273511727565

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 15.08.2025, 7:35 AM CEST

Data provider

This object is provided by:
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.

Show original at data provider

Associated

Kremer, Lea
Hennes, Elisabeth
Brause, Alexandra
Ursu, Andrei
Robke, Lucas
Matsubayashi, Hideaki T.
Nihongaki, Yuta
Flegel, Jana
Mejdrová, Ivana
Eickhoff, Jan
Baumann, Matthias
Nencka, Radim
Janning, Petra
Kordes, Susanne
Schöler, Hans R.
Sterneckert, Jared
Inoue, Takanari
Ziegler, Slava
Waldmann, Herbert

Other Objects (12)

Discovery of the Hedgehog Pathway Inhibitor Pipinib that Targets PI4KIIIß

Discovery of novel targets in the hedgehog signaling pathway

Using mechanistic Bayesian networks to identify downstream targets of the Sonic Hedgehog pathway

Identification and characterization of novel hedgehog signaling pathway inhibitors and their cellular targets

Hedgehog signaling pathway in ovarian cancer

A highlight on Sonic hedgehog pathway

Hochschulschrift

Histone deacetylase 6 represents a novel drug target in the oncogenic Hedgehog signaling pathway

Drugging Hedgehog: signaling the pathway to translation

The hedgehog pathway and ocular developmental anomalies

Hochschulschrift

Discovery of a novel form of Hedgehog that systemically circulates, and its signaling implications in Drosophila

The BET bromodomain inhibitor ZEN-3365 targets the Hedgehog signaling pathway in acute myeloid leukemia

Hedgehog pathway inhibitors – current status and future prospects

Discovery of the Hedgehog Pathway Inhibitor Pipinib that Targets PI4KIIIß

Discovery of novel targets in the hedgehog signaling pathway

Using mechanistic Bayesian networks to identify downstream targets of the Sonic Hedgehog pathway

Identification and characterization of novel hedgehog signaling pathway inhibitors and their cellular targets

Hedgehog signaling pathway in ovarian cancer

A highlight on Sonic hedgehog pathway

Hochschulschrift

Histone deacetylase 6 represents a novel drug target in the oncogenic Hedgehog signaling pathway

Drugging Hedgehog: signaling the pathway to translation

The hedgehog pathway and ocular developmental anomalies

Hochschulschrift

Discovery of a novel form of Hedgehog that systemically circulates, and its signaling implications in Drosophila

The BET bromodomain inhibitor ZEN-3365 targets the Hedgehog signaling pathway in acute myeloid leukemia

Hedgehog pathway inhibitors – current status and future prospects

Discovery of the Hedgehog Pathway Inhibitor Pipinib that Targets PI4KIIIß

Discovery of novel targets in the hedgehog signaling pathway

Using mechanistic Bayesian networks to identify downstream targets of the Sonic Hedgehog pathway

Identification and characterization of novel hedgehog signaling pathway inhibitors and their cellular targets

Hedgehog signaling pathway in ovarian cancer

A highlight on Sonic hedgehog pathway

Hochschulschrift

Histone deacetylase 6 represents a novel drug target in the oncogenic Hedgehog signaling pathway

Drugging Hedgehog: signaling the pathway to translation

The hedgehog pathway and ocular developmental anomalies

Hochschulschrift

Discovery of a novel form of Hedgehog that systemically circulates, and its signaling implications in Drosophila

The BET bromodomain inhibitor ZEN-3365 targets the Hedgehog signaling pathway in acute myeloid leukemia

Hedgehog pathway inhibitors – current status and future prospects

Cultural heritage institutions wishing to register will find more information here.

Fields marked * need to be filled in.

Username*

Please enter your username

Email*

Please enter your email address

Please do not fill this field

First name

Last name

Password*

Please enter your password

Confirm password*

Please enter the same password

I have read the terms of use and the privacy policy for the collection of personal data and accept them. *

This field is required.

I would like to subscribe to the newsletter of the Deutsche Digitale Bibliothek. See newsletter subscription info.

Account created

Your "My DDB" account has been successfully created. Before you can log in to your account, you must click the confirmation link in the message we just sent to the email address you provided.

Discovery of the Hedgehog Pathway Inhibitor Pipinib that Targets PI4KIIIß

Object Details

References and Relationships

Contributors, Places and Time

Further information

Data provider

Associated

Other Objects (12)

Discovery of the Hedgehog Pathway Inhibitor Pipinib that Targets PI4KIIIß

Discovery of novel targets in the hedgehog signaling pathway

Using mechanistic Bayesian networks to identify downstream targets of the Sonic Hedgehog pathway

Identification and characterization of novel hedgehog signaling pathway inhibitors and their cellular targets

Hedgehog signaling pathway in ovarian cancer

A highlight on Sonic hedgehog pathway

Histone deacetylase 6 represents a novel drug target in the oncogenic Hedgehog signaling pathway

Drugging Hedgehog: signaling the pathway to translation

The hedgehog pathway and ocular developmental anomalies

Discovery of a novel form of Hedgehog that systemically circulates, and its signaling implications in Drosophila

The BET bromodomain inhibitor ZEN-3365 targets the Hedgehog signaling pathway in acute myeloid leukemia

Hedgehog pathway inhibitors – current status and future prospects

Discovery of the Hedgehog Pathway Inhibitor Pipinib that Targets PI4KIIIß

Discovery of novel targets in the hedgehog signaling pathway

Using mechanistic Bayesian networks to identify downstream targets of the Sonic Hedgehog pathway

Identification and characterization of novel hedgehog signaling pathway inhibitors and their cellular targets

Hedgehog signaling pathway in ovarian cancer

A highlight on Sonic hedgehog pathway

Histone deacetylase 6 represents a novel drug target in the oncogenic Hedgehog signaling pathway

Drugging Hedgehog: signaling the pathway to translation

The hedgehog pathway and ocular developmental anomalies

Discovery of a novel form of Hedgehog that systemically circulates, and its signaling implications in Drosophila

The BET bromodomain inhibitor ZEN-3365 targets the Hedgehog signaling pathway in acute myeloid leukemia

Hedgehog pathway inhibitors – current status and future prospects

Discovery of the Hedgehog Pathway Inhibitor Pipinib that Targets PI4KIIIß

Discovery of novel targets in the hedgehog signaling pathway

Using mechanistic Bayesian networks to identify downstream targets of the Sonic Hedgehog pathway

Identification and characterization of novel hedgehog signaling pathway inhibitors and their cellular targets

Hedgehog signaling pathway in ovarian cancer

A highlight on Sonic hedgehog pathway

Histone deacetylase 6 represents a novel drug target in the oncogenic Hedgehog signaling pathway

Drugging Hedgehog: signaling the pathway to translation

The hedgehog pathway and ocular developmental anomalies

Discovery of a novel form of Hedgehog that systemically circulates, and its signaling implications in Drosophila

The BET bromodomain inhibitor ZEN-3365 targets the Hedgehog signaling pathway in acute myeloid leukemia

Hedgehog pathway inhibitors – current status and future prospects

Related objects

Reset password