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A diaminoantraquinone inhibitor of angiogenesis.
- Source :
-
The Journal of pharmacology and experimental therapeutics [J Pharmacol Exp Ther] 1994 Nov; Vol. 271 (2), pp. 1027-33. - Publication Year :
- 1994
-
Abstract
- Tumor growth is dependent upon angiogenesis. There is an intense search for pharmacological inhibitors of angiogenesis as a novel approach to treat angiogenic diseases, e.g., arthritis, diabetic retinopathy or cancer. A series of compounds, originally studied as potential protein kinase C inhibitors, included the diaminoanthraquinone NSC 639366 (1-[[3-(diethylamino)-2-hydroxypropyl]amino]-4-[(2,3- epoxypropyl)amino]-9,10-anthracenedione fumaric acid salt) (SPC-100097), was found to reversibly inhibit bovine endothelial cell growth with an IC50 that ranged between 1 and 4 nM. NSC 639366 reversibly inhibited endothelial cell migration, particularly endothelial cells stimulated by the potent angiogenic molecule, basic fibroblast growth factor. The activity of secreted urokinase-type plasminogen activator and active interstitial collagenase, but not gelatinase, was inhibited by NSC 639366. In vivo, angiogenesis was significantly inhibited by NSC 639366 by using the chick chorioallantoic membrane or the rat corneal bioassay. Two analogs of NSC 639366 did not inhibit endothelial cell growth. These experiments introduce a novel compound that could be clinically useful against angiogenic diseases and encourage further development of compounds that inhibit the plasminogen-plasmin system known to be a key regulator of angiogenesis.
- Subjects :
- Animals
Cattle
Cell Movement drug effects
Cells, Cultured
Chick Embryo
Endothelium, Vascular cytology
Endothelium, Vascular drug effects
Fibroblast Growth Factor 2 pharmacology
Male
Metalloendopeptidases metabolism
Plasminogen Activators metabolism
Rats
Rats, Wistar
Anthraquinones pharmacology
Neovascularization, Pathologic prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 0022-3565
- Volume :
- 271
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of pharmacology and experimental therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 7525934