Morphological profiling enables the identification of common mode of action for small molecules with different targets.

Morphological profiling enables the identification of common mode of action for small molecules with different targets.
Chembiochem. 2020 Jul 03;:
Authors: Schneidewind T, Brause A, Pahl A, Burhop A, Mejuch T, Sievers S, Waldmann H, Ziegler S
Abstract
Unbiased morphological profiling of bioactivity, e. g. in the cell painting assay (CPA), enables identification of small-molecule mode of action based on similarity to bioactivity of reference compounds and irrespective of biological target and chemical similarity. This is particularly important for small molecules with non-protein targets as those are rather difficult to identify with widely employed target identification methods. We employed morphological profiling using the CPA to identify compounds that are biosimilar to the iron chelator deferoxamine. Structurally different compounds with different annotated cellular targets provoked shared physiological response, thereby defining a cluster based on their morphological fingerprints. This cluster is based on a shared mode of action and not on a shared target, i.e. cell cycle modulation in the S or G2 phase. Hierarchical clustering of morphological fingerprints revealed subclusters that are based on mechanism of action and could be used to predict target-related bioactivity.
PMID: 32618075 [PubMed - as supplied by publisher]

Source: Chembiochem - July 2, 2020 Category: Biochemistry Authors: Schneidewind T, Brause A, Pahl A, Burhop A, Mejuch T, Sievers S, Waldmann H, Ziegler S Tags: Chembiochem Source Type: research