title: 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.
abstract: Choline kinase α (CHKA; here designated as ChoKα) 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 ChoKα 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 ChoKα 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 tumor-derived 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 ChoKα.
authors.affiliation: Traslational Oncology, Instituto de Investigación Sanitaria del Hospital Universitario La Paz, IdiPaz, Madrid, Spain. jclacal10@gmail.com.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Lacal
authors.affiliation: Department of Pharmaceutical and Organic Chemistry, University of Granada, Campus de Cartuja, Granada, Spain.
authors.forename: Joaquín M
authors.initials: JM
authors.lastname: Campos
mesh_terms: D000814:Aniline Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002797:Choline Kinase / Q000037:antagonists & inhibitors*; D045325:HCT116 Cells; D019073:HT29 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D007274:Injections, Intraperitoneal; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011806:Quinolinium Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D011806:Quinolinium Compounds; C000593610:RSM-932A; C517212:CHKA protein, human; D002797:Choline Kinase