COTI-2, a novel small molecule that is active against multiple human cancer cell linesin vitroandin vivo

// Kowthar Y. Salim 1, * , Saman Maleki Vareki 2, * , Wayne R. Danter 1 , Serban San-Marina 7 and James Koropatnick 2, 3, 4, 5, 6 1 Critical Outcome Technologies Inc., London, Ontario, Canada 2 Cancer Research Laboratory Program, Lawson Health Research Institute, London, Ontario, Canada 3 Department of Microbiology and Immunology, Western University, London, Ontario, Canada 4 Department of Pathology, Western University, London, Ontario, Canada 5 Department of Oncology, Western University, London, Ontario, Canada 6 Department of Physiology and Pharmacology, Western University, London, Ontario, Canada 7 Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic School of Medicine, Rochester, Minnesota, USA * These authors have contributed equally to this work Correspondence to: James Koropatnick, email: jkoropat@uwo.ca Keywords: COTI-2, CHEMSAS, targeted-therapy, cancer, small molecule Received: February 18, 2016     Accepted: April 16, 2016     Published: May 2, 2016 ABSTRACT Identification of novel anti-cancer compounds with high efficacy and low toxicity is critical in drug development. High-throughput screening and other such strategies are generally resource-intensive. Therefore, in silico computer-aided drug design has gained rapid acceptance and popularity. We employed our proprietary computational platform (CHEMSAS ® ), which uses a unique combination of traditional and modern pharmacology principles, statistical modeling, medicinal chemistry, and machine-learning technologies to discover and optimize novel compounds that could target various cancers. COTI-2 is a small molecule candidate anti-cancer drug identified using CHEMSAS. This study describes the in vitro and in vivo evaluation of COTI-2. Our data demonstrate that COTI-2 is effective against a diverse group of human cancer cell lines regardless of their tissue of origin or genetic makeup. Most treated cancer cell lines were sensitive to COTI-2 at nanomolar concentrations. When compared to traditional chemotherapy or targeted-therapy agents, COTI-2 showed superior activity against tumor cells, in vitro and in vivo . Despite its potent anti-tumor efficacy, COTI-2 was safe and well-tolerated in vivo. Although the mechanism of action of COTI-2 is still under investigation, preliminary results indicate that it is not a traditional kinase or an Hsp90 inhibitor.