Display options
Cite
Akbarzadeh M, Deipenwisch I, Schoelermann B, et al. Morphological profiling by means of the Cell Painting assay enables identification of tubulin-targeting compounds. Cell Chem Biol. 2021;doi: 10.1016/j.chembiol.2021.12.009.
Akbarzadeh, M., Deipenwisch, I., Schoelermann, B., Pahl, A., Sievers, S., Ziegler, S., & Waldmann, H. (2021). Morphological profiling by means of the Cell Painting assay enables identification of tubulin-targeting compounds. Cell chemical biology, . https://doi.org/10.1016/j.chembiol.2021.12.009
Akbarzadeh, Mohammad, et al. "Morphological profiling by means of the Cell Painting assay enables identification of tubulin-targeting compounds." Cell chemical biology vol. (2021). doi: https://doi.org/10.1016/j.chembiol.2021.12.009
Akbarzadeh M, Deipenwisch I, Schoelermann B, Pahl A, Sievers S, Ziegler S, Waldmann H. Morphological profiling by means of the Cell Painting assay enables identification of tubulin-targeting compounds. Cell Chem Biol. 2021 Dec 21; doi: 10.1016/j.chembiol.2021.12.009. Epub 2021 Dec 21. PMID: 34968420.
Copy Download .nbib Format: NLM
Share it on

Cell Chem Biol. 2021 Dec 21; doi: 10.1016/j.chembiol.2021.12.009. Epub 2021 Dec 21.

Morphological profiling by means of the Cell Painting assay enables identification of tubulin-targeting compounds.

Cell chemical biology

Mohammad Akbarzadeh, Ilka Deipenwisch, Beate Schoelermann, Axel Pahl, Sonja Sievers, Slava Ziegler, Herbert Waldmann

Affiliations

  1. Max-Planck-Institut für Molekulare Physiologie, Abteilung Chemische Biologie, Otto-Hahn-Straße 11, Dortmund 44227, Germany.
  2. Max-Planck-Institut für Molekulare Physiologie, Abteilung Chemische Biologie, Otto-Hahn-Straße 11, Dortmund 44227, Germany. Electronic address: [email protected].
  3. Max-Planck-Institut für Molekulare Physiologie, Abteilung Chemische Biologie, Otto-Hahn-Straße 11, Dortmund 44227, Germany; Technische Universität Dortmund, Fakultät Chemie und Chemische Biologie, Otto-Hahn-Straße 6, Dortmund 44221, Germany. Electronic address: [email protected].

PMID: 34968420 DOI: 10.1016/j.chembiol.2021.12.009

Abstract

In phenotypic compound discovery, conclusive identification of cellular targets and mode of action are often impaired by off-target binding. In particular, microtubules are frequently targeted in cellular assays. However, in vitro tubulin binding assays do not correctly reflect the cellular context, and conclusive high-throughput phenotypic assays monitoring tubulin binding are scarce, such that tubulin binding is rarely identified. We report that morphological profiling using the Cell Painting assay (CPA) can efficiently detect tubulin modulators in compound collections with a high throughput, including annotated reference compounds and unannotated compound classes with unrelated chemotypes and scaffolds. Small-molecule tubulin binders share similar CPA fingerprints, which enables prediction and experimental validation of microtubule-binding activity. Our findings suggest that CPA or a related morphological profiling approach will be an invaluable addition to small-molecule discovery programs in chemical biology and medicinal chemistry, enabling early identification of one of the most frequently observed off-target activities.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Keywords: Cell Painting assay; microtubules; morphology; profiling; small molecules; tubulin

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Publication Types