COTI-2, a novel small molecule that is active against multiple human cancer cell lines in vitro and in vivo
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Kowthar Y. Salim1,*, Saman Maleki Vareki2,*, Wayne R. Danter1, Serban San-Marina7 and James Koropatnick2,3,4,5,6
1Critical Outcome Technologies Inc., London, Ontario, Canada
2Cancer Research Laboratory Program, Lawson Health Research Institute, London, Ontario, Canada
3Department of Microbiology and Immunology, Western University, London, Ontario, Canada
4Department of Pathology, Western University, London, Ontario, Canada
5Department of Oncology, Western University, London, Ontario, Canada
6Department of Physiology and Pharmacology, Western University, London, Ontario, Canada
7Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic School of Medicine, Rochester, Minnesota, USA
*These authors have contributed equally to this work
James Koropatnick, email: email@example.com
Keywords: COTI-2, CHEMSAS, targeted-therapy, cancer, small molecule
Received: February 18, 2016 Accepted: April 16, 2016 Published: May 2, 2016
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.
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