Abstract |
DMU-135 (3,4-Methylenedioxy-3',4',5'-trimethoxy chalcone) is a novel anticancer prodrug designed to be activated into a potent tyrosine kinase inhibitor by the tumour selective enzyme activity of the cytochrome P450 enzyme CYP1B1. CYP1B1 is selectively expressed in a wide variety of tumours including colon. The hypothesis was tested that DMU-135 would inhibit Apc(Min/+) mouse gastrointestinal adenoma formation. From 4-18 weeks of age animals received DMU-135 (0.2% w:w) in AIN93G diet. DMU-135 was well tolerated, induced no systemic side-effects and reduced adenoma multiplicity by 46 +/- 18.3% compared to controls (p < 0.001). Further characterisation of this promising chemopreventive agent is required.
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Authors | S Sale, R G Tunstall, K C Ruparelia, P C Butler, G A Potter, W P Steward, A J Gescher |
Journal | Investigational new drugs
(Invest New Drugs)
Vol. 24
Issue 6
Pg. 459-64
(Nov 2006)
ISSN: 0167-6997 [Print] United States |
PMID | 16505954
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 3,4-methylenedioxy-3',4',5'-trimethoxy chalcone
- Antineoplastic Agents
- Prodrugs
- Chalcone
- Protein-Tyrosine Kinases
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Topics |
- Adenoma
(pathology, prevention & control)
- Animals
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Chalcone
(analogs & derivatives, pharmacology, therapeutic use)
- Colon
(drug effects, pathology)
- Disease Models, Animal
- Genes, APC
- Hematocrit
- Intestinal Neoplasms
(pathology, prevention & control)
- Intestine, Small
(drug effects, pathology)
- Mice
- Mice, Inbred C57BL
(genetics)
- Prodrugs
(pharmacology, therapeutic use)
- Protein-Tyrosine Kinases
(antagonists & inhibitors)
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