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

doi:10.1007/s10637-014-0144-z

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

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1105-1112
Number of pages	8
Journal	Investigational New Drugs
Volume	32
Issue number	6
DOIs	https://doi.org/10.1007/s10637-014-0144-z
State	Published - Dec 1 2014

Keywords

CG100649
COX-2
Carbonic anhydrase-I/-II
Celecoxib
Colorectal cancer
PGE

ASJC Scopus subject areas

Oncology
Pharmacology
Pharmacology (medical)

MD Anderson CCSG core facilities

Research Animal Support Facility

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10.1007/s10637-014-0144-z

Cite this

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

abstract = "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 = "CG100649, COX-2, Carbonic anhydrase-I/-II, Celecoxib, Colorectal cancer, PGE",

author = "Kim, {Sun Hee} and Ofer Margalit and Hiroshi Katoh and Dingzhi Wang and Hong Wu and Dianren Xia and Holla, {Vijaykumar R.} and Peiying Yang and Dubois, {Raymond N.}",

note = "Funding Information: 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). Publisher Copyright: {\textcopyright} 2014 Springer Science+Business Media New York.",

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doi = "10.1007/s10637-014-0144-z",

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AU - Kim, Sun Hee

AU - Margalit, Ofer

AU - Katoh, Hiroshi

AU - Wang, Dingzhi

AU - Wu, Hong

AU - Xia, Dianren

AU - Holla, Vijaykumar R.

AU - Yang, Peiying

AU - Dubois, Raymond N.

N1 - Funding Information: 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). Publisher Copyright: © 2014 Springer Science+Business Media New York.

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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