Phenotyping Reveals Targets of a Pseudo‐Natural‐Product Autophagy Inhibitor

to related objects

Abstract: Pseudo‐natural‐product (NP) design combines natural product fragments to provide unprecedented NP‐inspired compounds not accessible by biosynthesis, but endowed with biological relevance. Since the bioactivity of pseudo‐NPs may be unprecedented or unexpected, they are best evaluated in target agnostic cell‐based assays monitoring entire cellular programs or complex phenotypes. Here, the Cinchona alkaloid scaffold was merged with the indole ring system to synthesize indocinchona alkaloids by Pd‐catalyzed annulation. Exploration of indocinchona alkaloid bioactivities in phenotypic assays revealed a novel class of azaindole‐containing autophagy inhibitors, the azaquindoles. Subsequent characterization of the most potent compound, azaquindole‐1, in the morphological cell painting assay, guided target identification efforts. In contrast to the parent Cinchona alkaloids, azaquindoles selectively inhibit starvation‐ and rapamycin‐induced autophagy by targeting the lipid kinase VPS34.

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Bibliographic citation: Phenotyping Reveals Targets of a Pseudo‐Natural‐Product Autophagy Inhibitor ; volume:59 ; number:30 ; year:2020 ; pages:12470-12476 ; extent:7
Angewandte Chemie / International edition. International edition ; 59, Heft 30 (2020), 12470-12476 (gesamt 7)

Creator: Foley, Daniel J.
Zinken, Sarah
Corkery, Dale
Laraia, Luca
Pahl, Axel
Wu, Yaowen
Waldmann, Herbert

DOI: 10.1002/anie.202000364

URN: urn:nbn:de:101:1-2022062006382198746957

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

Last update: 15.08.2025, 7:23 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

Foley, Daniel J.
Zinken, Sarah
Corkery, Dale
Laraia, Luca
Pahl, Axel
Wu, Yaowen
Waldmann, Herbert

Other Objects (12)

Phenotyping Reveals Targets of a Pseudo‐Natural‐Product Autophagy Inhibitor

Phenotyping Reveals Targets of a Pseudo‐Natural‐Product Autophagy Inhibitor

Deep phenotyping reveals movement phenotypes in mouse neurodevelopmental models

Deep phenotyping reveals movement phenotypes in mouse neurodevelopmental models

Spectral phenotyping of embryonic development reveals integrative thermodynamic responses

Spectral phenotyping of embryonic development reveals integrative thermodynamic responses

PSEUDO-SEMIDIRECT PRODUCT OF THE ABSTRACT OBJECTS

PSEUDO-SEMIDIRECT PRODUCT OF THE ABSTRACT OBJECTS

The Pseudo‐Natural Product Rhonin Targets RHOGDI

The Pseudo‐Natural Product Rhonin Targets RHOGDI

The Pseudo‐Natural Product Rhonin Targets RHOGDI

The Pseudo‐Natural Product Rhonin Targets RHOGDI

TEST SPACES, PSEUDO-EFFECT ALGEBRAS, AND TENSOR PRODUCT OF PSEUDO-EFFECT ALGEBRAS

TEST SPACES, PSEUDO-EFFECT ALGEBRAS, AND TENSOR PRODUCT OF PSEUDO-EFFECT ALGEBRAS

Combination of Pseudo‐Natural Product Design and Formal Natural Product Ring Distortion Yields Stereochemically and Biologically Diverse Pseudo‐Sesquiterpenoid Alkaloids

Combination of Pseudo‐Natural Product Design and Formal Natural Product Ring Distortion Yields Stereochemically and Biologically Diverse Pseudo‐Sesquiterpenoid Alkaloids

Combination of Pseudo‐Natural Product Design and Formal Natural Product Ring Distortion Yields Stereochemically and Biologically Diverse Pseudo‐Sesquiterpenoid Alkaloids

Combination of Pseudo‐Natural Product Design and Formal Natural Product Ring Distortion Yields Stereochemically and Biologically Diverse Pseudo‐Sesquiterpenoid Alkaloids

Lipidomic Phenotyping Reveals Extensive Lipid Remodeling during Adipogenesis in Human Adipocytes

Lipidomic Phenotyping Reveals Extensive Lipid Remodeling during Adipogenesis in Human Adipocytes

Combinatorial CRISPR screening reveals functional buffering in autophagy

Combinatorial CRISPR screening reveals functional buffering in autophagy

Pseudo Natural Products—Chemical Evolution of Natural Product Structure

Pseudo Natural Products—Chemical Evolution of Natural Product Structure

Phenotyping Reveals Targets of a Pseudo‐Natural‐Product Autophagy Inhibitor

Phenotyping Reveals Targets of a Pseudo‐Natural‐Product Autophagy Inhibitor

Deep phenotyping reveals movement phenotypes in mouse neurodevelopmental models

Deep phenotyping reveals movement phenotypes in mouse neurodevelopmental models

Spectral phenotyping of embryonic development reveals integrative thermodynamic responses

Spectral phenotyping of embryonic development reveals integrative thermodynamic responses

PSEUDO-SEMIDIRECT PRODUCT OF THE ABSTRACT OBJECTS

PSEUDO-SEMIDIRECT PRODUCT OF THE ABSTRACT OBJECTS

The Pseudo‐Natural Product Rhonin Targets RHOGDI

The Pseudo‐Natural Product Rhonin Targets RHOGDI

The Pseudo‐Natural Product Rhonin Targets RHOGDI

The Pseudo‐Natural Product Rhonin Targets RHOGDI

TEST SPACES, PSEUDO-EFFECT ALGEBRAS, AND TENSOR PRODUCT OF PSEUDO-EFFECT ALGEBRAS

TEST SPACES, PSEUDO-EFFECT ALGEBRAS, AND TENSOR PRODUCT OF PSEUDO-EFFECT ALGEBRAS

Combination of Pseudo‐Natural Product Design and Formal Natural Product Ring Distortion Yields Stereochemically and Biologically Diverse Pseudo‐Sesquiterpenoid Alkaloids

Combination of Pseudo‐Natural Product Design and Formal Natural Product Ring Distortion Yields Stereochemically and Biologically Diverse Pseudo‐Sesquiterpenoid Alkaloids

Combination of Pseudo‐Natural Product Design and Formal Natural Product Ring Distortion Yields Stereochemically and Biologically Diverse Pseudo‐Sesquiterpenoid Alkaloids

Combination of Pseudo‐Natural Product Design and Formal Natural Product Ring Distortion Yields Stereochemically and Biologically Diverse Pseudo‐Sesquiterpenoid Alkaloids

Lipidomic Phenotyping Reveals Extensive Lipid Remodeling during Adipogenesis in Human Adipocytes

Lipidomic Phenotyping Reveals Extensive Lipid Remodeling during Adipogenesis in Human Adipocytes

Combinatorial CRISPR screening reveals functional buffering in autophagy

Combinatorial CRISPR screening reveals functional buffering in autophagy

Pseudo Natural Products—Chemical Evolution of Natural Product Structure

Pseudo Natural Products—Chemical Evolution of Natural Product Structure

Phenotyping Reveals Targets of a Pseudo‐Natural‐Product Autophagy Inhibitor

Phenotyping Reveals Targets of a Pseudo‐Natural‐Product Autophagy Inhibitor

Deep phenotyping reveals movement phenotypes in mouse neurodevelopmental models

Deep phenotyping reveals movement phenotypes in mouse neurodevelopmental models

Spectral phenotyping of embryonic development reveals integrative thermodynamic responses

Spectral phenotyping of embryonic development reveals integrative thermodynamic responses

PSEUDO-SEMIDIRECT PRODUCT OF THE ABSTRACT OBJECTS

PSEUDO-SEMIDIRECT PRODUCT OF THE ABSTRACT OBJECTS

The Pseudo‐Natural Product Rhonin Targets RHOGDI

The Pseudo‐Natural Product Rhonin Targets RHOGDI

The Pseudo‐Natural Product Rhonin Targets RHOGDI

The Pseudo‐Natural Product Rhonin Targets RHOGDI

TEST SPACES, PSEUDO-EFFECT ALGEBRAS, AND TENSOR PRODUCT OF PSEUDO-EFFECT ALGEBRAS

TEST SPACES, PSEUDO-EFFECT ALGEBRAS, AND TENSOR PRODUCT OF PSEUDO-EFFECT ALGEBRAS

Combination of Pseudo‐Natural Product Design and Formal Natural Product Ring Distortion Yields Stereochemically and Biologically Diverse Pseudo‐Sesquiterpenoid Alkaloids

Combination of Pseudo‐Natural Product Design and Formal Natural Product Ring Distortion Yields Stereochemically and Biologically Diverse Pseudo‐Sesquiterpenoid Alkaloids

Combination of Pseudo‐Natural Product Design and Formal Natural Product Ring Distortion Yields Stereochemically and Biologically Diverse Pseudo‐Sesquiterpenoid Alkaloids

Combination of Pseudo‐Natural Product Design and Formal Natural Product Ring Distortion Yields Stereochemically and Biologically Diverse Pseudo‐Sesquiterpenoid Alkaloids

Lipidomic Phenotyping Reveals Extensive Lipid Remodeling during Adipogenesis in Human Adipocytes

Lipidomic Phenotyping Reveals Extensive Lipid Remodeling during Adipogenesis in Human Adipocytes

Combinatorial CRISPR screening reveals functional buffering in autophagy

Combinatorial CRISPR screening reveals functional buffering in autophagy

Pseudo Natural Products—Chemical Evolution of Natural Product Structure

Pseudo Natural Products—Chemical Evolution of Natural Product Structure

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.