The anticancer drug candidate 1,3-di(p-methoxybenzyl)-4,5-di(p-isopropylphenyl)-imidazol-2-ylidene copper(
I) bromide (WBC4) was tested on the NCI 60 cancer cell panel in vitro. WBC4 showed very good activity against a
wide range of human cancer cell lines inclusive renal cell cancer with an average GI50 value of 288 nM. This encouraged
maximum tolerable dose (MTD) experiments in mice, where a MTD value of 10 mg/kg was determined with single injections
to groups of 2 mice. In the following tumor xenograft experiment WBC4 was given at 5 and 10 mg/kg in 5 injections
to two cohorts of 6 CAKI-1 tumor-bearing NMRI:nu/nu mice, while a control cohort of 6 mice was treated with solvent
only. At the higher dose of 10 mg/kg WBC4 showed borderline toxicity leading to 2 mortalities, while a significant T/C
value of 0.38 was observed on day 32. At the lower dose of 5 mg/kg WBC4 induced mild and reversible body weight loss
with no toxic deaths. At this dose WBC4 showed an identical significant T/C value of 0.38 on day 32, when compared to
the treatment group. Immunohistochemistry for the proliferation marker Ki-67 did not show significant changes due to
WBC4 treatment in the animals. However, anti-angiogenic effects by WBC4 treatment were observed in CD31 immunohistochemistry.
Here, significant reduction in microvessel number, area and ratio was determined in tumors treated with
10 mg/kg of WBC4.