Identification of new Erb B 4 inhibitors by inverse virtual screening

We have applied the inverse virtual screening protocol to a small library of 19 synthetic compounds that showed a weak activity against the enzyme JMJD3. Our analysis suggested the enzyme ErbB4 as a new putative target of the investigated compounds. This macromolecule is a receptor tyrosine-protein kinase, member of the epidermal growth factor receptor subfamily and identified as potential target for cancer therapy. Experimental in vitro assays show that 5 compounds present inhibitory activity against ErbB4 in the low micromolar range. We have also investigated the binding of the identified lead compounds toward the highly structural related isoform ErbB2. The experimental evidences highlight a selectivity towards ErbB4. Moreover, one of the selected compounds shows antiproliferative activity against carcinoma (HCT) and breast (MCF7) cancer cells in low micromolar range