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01.12.2014 | PRECLINICAL STUDIES | Ausgabe 6/2014

Investigational New Drugs 6/2014

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

Zeitschrift:
Investigational New Drugs > Ausgabe 6/2014
Autoren:
Sun-Hee Kim, Ofer Margalit, Hiroshi Katoh, Dingzhi Wang, Hong Wu, Dianren Xia, Vijaykumar R. Holla, Peiying Yang, Raymond N. DuBois
Wichtige Hinweise
Sun-Hee Kim and Ofer Margalit are contributed equally to this work.

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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