Research Papers:

This article has been corrected. Correction in: Oncotarget. 2017; 8:60724.

COTI-2, a novel small molecule that is active against multiple human cancer cell lines in vitro and in vivo

Kowthar Y. Salim _, Saman Maleki Vareki, Wayne R. Danter, Serban San-Marina and James Koropatnick

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Oncotarget. 2016; 7:41363-41379. https://doi.org/10.18632/oncotarget.9133

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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

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


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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