Investigational New Drugs

, Volume 32, Issue 6, pp 1105–1112

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

  • Sun-Hee Kim
  • Ofer Margalit
  • Hiroshi Katoh
  • Dingzhi Wang
  • Hong Wu
  • Dianren Xia
  • Vijaykumar R. Holla
  • Peiying Yang
  • Raymond N. DuBois
PRECLINICAL STUDIES

DOI: 10.1007/s10637-014-0144-z

Cite this article as:
Kim, S., Margalit, O., Katoh, H. et al. Invest New Drugs (2014) 32: 1105. doi:10.1007/s10637-014-0144-z

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.

Keywords

Colorectal cancerCOX-2CG100649CelecoxibPGE2Carbonic anhydrase-I/-II

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Sun-Hee Kim
    • 1
  • Ofer Margalit
    • 2
  • Hiroshi Katoh
    • 2
  • Dingzhi Wang
    • 2
  • Hong Wu
    • 1
  • Dianren Xia
    • 1
  • Vijaykumar R. Holla
    • 1
  • Peiying Yang
    • 3
  • Raymond N. DuBois
    • 2
    • 4
  1. 1.Departments of Cancer BiologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Laboratory for Inflammation and CancerArizona State University Biodesign Institute TempeUSA
  3. 3.Departments of General OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  4. 4.Department of Research and Division of GastroenterologyScottsdaleUSA