TY  - JOUR
AU  - Ortín, Irene
AU  - Ochoa-Callejero, Laura
AU  - Werner, Christian
AU  - Lindenblatt, Dirk
AU  - Niefind, Karsten
AU  - Martínez, Alfredo
AU  - de Pascual-Teresa, Beatriz
AU  - Ramos, Ana Sofia
TI  - Targeting Casein Kinase 2 and Histone Deacetylase with a Dual Inhibitor Effectively Reduces Tumor Growth in a Triple-Negative Breast Cancer Xenograft Model
JO  - ACS pharmacology & translational science
VL  - 8
IS  - 7
SN  - 2575-9108
CY  - Washington, DC
PB  - ACS Publications
M1  - PUBDB-2025-04033
SP  - 2093 - 2105
PY  - 2025
N1  - Deutsche Forschungsgemeinschaft (DFG), grants NI 643/4-1 and NI 643/11-1.  Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Grant No. INST 216/682-1 FUGG. 
AB  - 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.
LB  - PUB:(DE-HGF)16
DO  - DOI:10.1021/acsptsci.5c00192
UR  - https://bib-pubdb1.desy.de/record/638315
ER  -