Journal Article

PUBDB-2025-04033

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Targeting Casein Kinase 2 and Histone Deacetylase with a Dual Inhibitor Effectively Reduces Tumor Growth in a Triple-Negative Breast Cancer Xenograft Model

Ortín, I. ; Ochoa-Callejero, L. ; Werner, C. ; Lindenblatt, D. ; Niefind, K.Extern*EMBL* ; Martínez, A. (Corresponding author) ; de Pascual-Teresa, B. (Corresponding author) ; Ramos, A. (Corresponding author)

2025
ACS Publications Washington, DC

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Please use a persistent id in citations: doi:10.1021/acsptsci.5c00192

Abstract: In a previous study, IOR-160 was identified as a potent dual inhibitor of CK2 and HDAC enzymes. In this study, we evaluated its selectivity and therapeutic potential. IOR-160 exhibited high selectivity for CK2 within a panel of 21 kinases and more widespread inhibitory activity against histone deacetylases (HDAC 1, 2, 3, and 6, low activity for HDAC8). Using a mouse model of triple-negative breast cancer (MDA-MB-231), we further explored its effects on disease progression. Notably, animals treated with IOR-160 exhibited no detectable signs of toxicity or behavioral side effects relative to untreated mice. In a xenograft study, IOR-160 significantly reduced tumor growth (p = 0.0336) and decreased tumor burden (p = 0.0454) compared to the vehicle (DMSO)-treated group. In addition, IOR-160 modulated critical cellular signaling pathways, demonstrated by the inhibition of AKT phosphorylation (p = 0.0175) and a significant increase in acetylated α-tubulin (p = 0.0023), confirming the dual action of IOR-160in vivo. Furthermore, X-ray crystallography revealed the binding mode of IOR-160 to CK2, showing high conservation compared to that of the known CK2 inhibitor CX-4945. These results suggest that IOR-160 has significant potential as an antitumor agent. Nonclinical and clinical studies become now necessary to validate the efficacy of this new chemical entity as a potential drug.

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Contributing Institute(s):

1. EMBL-User (EMBL-User)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)

Experiment(s):

1. PETRA Beamline P13 (PETRA III)

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Emerging Sources Citation Index ; IF >= 5 ; JCR ; SCOPUS ; Web of Science Core Collection

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