Over the past decade, it has become abundantly clear that cancer-initiating stem cell (CSC) elimination is imperative to ?cure? cancer. Unfortunately, most of the existing clinical therapies target the bulk tumor and spare the very small number CSCs comprising <~1% of tumor, which expand after completion of therapy and cause relapse. Transgenex Nanobiotech Inc. (TGN) R & D has demonstrated the feasibility of targeting natriuretic peptide receptor A (NPRA) to cease tumor progression, however NPRA?s role in CSCs was unclear. In the phase I contract, TGN scientists developed a library of small molecules by computer modelling and screened them for their capacity to target CSC. This led to identification and validation of compound #2, heretofore designated NRI20152, as a bona-fide inhibitor of NPRA. NRI20152 showed anti-CSC activity in 3 generations of sphere-forming assays and it showed no harmful effect in mice in the pilot acute toxicity studies.
