UNBS 5162

UNBS5162 is a pan-antagonist of CXCL chemokines. By using the MTT colorimetric assay, IC50 values of the mean antiproliferative activity against nine human cancer cell lines were 19.8 and 17.9 μ M for UNBS3157 and UNBS5162, respectively.
 CXCL chemokines is composed of a CXC chemokine domain, a mucin-like stalk, a transmembrane domain and a cytoplasmic tail containing a potential tyrosine phosphorylation site that may bind SH2.
UNBS5162 display weak antiproliferative activity in vitro.
UNBS5162 increases the therapeutic benefits of taxol in the orthotopic human PC-3 prostate cancer model. The proliferation of PC-3 cell and DU-145 prostate cancer cells were prevented by 10 μM UNBS5162 in vitro after the 6-day treatment. Flow cytometry analysis revealed that treatment of PC-3 and DU-145 cells with 10 μM UNBS5162 for 72 hours markedly blocked PC-3 cells in their G2 cell cycle phase and to a lesser extent in DU-145 cells. The percentage of PC-3 cells in the G2/M phase markedly increased, and accordingly the percentage of cells in the G1 phase diminished. The Rb protein expression in PC-3 cells was completely abolished after 48 and 72 hours treatment of 10 μM UNBS5162.
The cell cycle kinetics of PC-3 or DU-145 was not significantly modified by 1 μM UNBS5162. UNBS5162 at 1 μM induced no marked modifications in Rb, pRb, and E2F1 protein expression. UNBS5162 at concentrations higher than 1 μM was toxic, as indicated by inhibited proliferation of murine and human hematopoietic stem and progenitor cells
References:
[1]. Mijatovic T, Mahieu T, Bruyère C et al. UNBS5162, a novel naphthalimide that decreases CXCL chemokine expression in experimental prostate cancers. Neoplasia. 2008 Jun;10(6):573-86.