Preclinical Characterization of RSM-932A, a Novel Anticancer Drug Targeting the Human Choline Kinase Alpha, an Enzyme Involved in Increased Lipid Metabolism of Cancer Cells

Choline kinase alpha (CHKA; here designated as ChoK alpha) is the first enzyme in the CDP-choline pathway, implicated in phospholipids metabolism. It is overexpressed in several human tumors such as breast, lung, bladder, colorectal, prostate, ovary, and liver. The overexpression of ChoK alpha has oncogenic potential and synergizes with other known oncogenes. It has been proposed as a novel cancer drug target with a distinct mechanism of action. We have generated a set of ChoK alpha inhibitors with potent in vitro antiproliferative and in vivo antitumoral activity against human xenografts in mice, showing high efficacy with low toxicity profiles. Among these inhibitors, RSM-932A has been chosen for further clinical development due to its potent antiproliferative activity in vitro against a large variety of tumorderived cell lines, a potent in vivo anticancer activity, and lack of toxicity at the effective doses. Here, we provide the preclinical evidence to support the use of RSM-932A as a good candidate to be tested in clinical trials as the "first in humans" drug targeting ChoKa. (C) 2014 AACR.