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CG100649, a novel COX-2 inhibitor, inhibits colorectal adenoma and carcinoma growth in mouse models

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Summary

Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors (COXIBs) can reduce the risk of developing colorectal cancer (CRC) and are being considered for use as adjuvant therapy for treatment of CRC patients. However, long-term use of most NSAIDs, except aspirin, increases cardiovascular risk, hampering use of these drugs in CRC prevention and possibly for treatment. CG100649 is a new member of the COXIB family, which is proposed to inhibit both COX-2 and carbonic anhydrase-I/-II (CA-I/-II) activity. Using mouse models, we show here that CG100649 inhibits premalignant and malignant colorectal lesions in mouse models, partly through inhibiting tumor cell proliferation. These pre-clinical findings suggest a need for further exploration of CG100649 for CRC prevention and treatment. The long-term safety profile of CG100649, particularly regarding its effect on cardiovascular risk, is yet to be determined.

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Acknowledgments

This work was supported, in part, by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grants R37-DK047297] (to R.N.D); and the National Cancer Institute [Grant P01-CA077839, R01 CA184820] (to R.N.D). We also thank the National Colorectal Cancer Research Alliance (NCCRA) for its generous support (to R.N.D).

Conflict of Interest

All authors declare that they have no conflict of interest.  No financial support from CrystalGenomics Inc. was provided for these studies.

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Authors and Affiliations

  1. Departments of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Sun-Hee Kim, Hong Wu, Dianren Xia & Vijaykumar R. Holla

  2. Laboratory for Inflammation and Cancer, Arizona State University Biodesign Institute , Tempe, AZ, USA

    Ofer Margalit, Hiroshi Katoh, Dingzhi Wang & Raymond N. DuBois

  3. Departments of General Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Peiying Yang

  4. Department of Research and Division of Gastroenterology, Mayo Clinic, Scottsdale, AZ, USA

    Raymond N. DuBois

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  1. Sun-Hee Kim
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  2. Ofer Margalit
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Correspondence to Raymond N. DuBois.

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Sun-Hee Kim and Ofer Margalit are contributed equally to this work.

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Kim, SH., Margalit, O., Katoh, H. et al. CG100649, a novel COX-2 inhibitor, inhibits colorectal adenoma and carcinoma growth in mouse models. Invest New Drugs 32, 1105–1112 (2014). https://doi.org/10.1007/s10637-014-0144-z

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  • DOI: https://doi.org/10.1007/s10637-014-0144-z

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