IC50: 1.7-4.0 μM for tested cancer cell lines
NSC348884 is a nucleophosmin inhibitor.
Nucleophosmin is identified as a multifunctional nucleolar phosphoprotein, which is dysregulated in human malignancies resulting in anti-apoptosis and differentiation inhibition.
In vitro: NSC348884, which was identified as a putative nucleophosmin small molecular inhibitor, was found to be able to disrupt a hydrophobic pocket that was required for oligomerization, and NSC348884 could also inhibit the cell proliferation in distinct cancer cell lines and disrupt nucleophosmin oligomer formation. Moreover, the treatment of several cancer cell types with NSC348884 could dose-dependently upregulate p53 and also induce apoptosis that correlated with H2AX phosphorylation, poly(ADP-ribose) polymerase cleavage as well as Annexin V. Furthermore, NSC348884 could also synergize doxorubicin cytotoxicity on the viability of cancer cells [1].
In vivo: Previous study showed that the in-vivo intravasation and invasion could be significantly inhibited after the injection of NSC348884 into the tumor-bearing mice. In addition, there was no significant difference in overall cell death that was observed by histology in the treated tumors with the 4-hour brief treatments, indicating that the inhibition seen was specific to migration [2].
Clinical trial: Up to now, NSC348884 is still in the preclinical development stage.
References:
[1] Qi W,Shakalya K,Stejskal A,Goldman A,Beeck S,Cooke L,Mahadevan D. NSC348884, a nucleophosmin inhibitor disrupts oligomer formation and induces apoptosis in human cancer cells. Oncogene.2008 Jul 10;27(30):4210-20.
[2] Patsialou A,Wang Y,Lin J,Whitney K,Goswami S,Kenny PA,Condeelis JS. Selective gene-expression profiling of migratory tumor cells in vivo predicts clinical outcome in breast cancer patients. Breast Cancer Res.2012 Oct 31;14(5):R139.