Three novel synthetic retinoids, Re 80, Am 580 and Am 80, all exhibit anti-angiogenic activity in vivo.
In a previous study, we demonstrated that retinoic acid or a synthetic retinoid, Ch 55 ((E)-4-[3-(3,5-di-tert-butylphenyl)-3-oxo-1-propenyl]benzoic acid), significantly affects in vivo angiogenesis, on the basis of our working hypothesis that a cell differentiation modulator could also exhibit anti-angiogenic activity. In the present study, three novel synthetic retinoids, Re 80 (4-[1-hydroxy-3-oxo-3-(5,6,7,8-tetrahydro-3-hydroxy-5,5,8,8-tetramethyl- 2- naphthalenyl)-1-propenyl]benzoic acid), Am 580 (4-[(5,6,7,8-tetrahydro- 5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]benzoic acid) and Am 80 (4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl] benzoic acid), whose cell differentiation-modulating effects are roughly comparable to or more potent than that of Ch 55, which was the most effective angiostatic retinoid identified previously, were examined. Their anti-angiogenic effects were tested in an in vivo assay system involving chorioallantoic membranes of growing chick embryos. They were all found to exert dose-dependent anti-angiogenic effects in the picomolar range. Their rank order for inhibitory potency was Re 80 > Am 580 > Am 80, the ID50 values being 6.3, 23 and 28 pmol/egg, respectively. These results indicate that treatment involving these three novel synthetic retinoids might have potential therapeutic efficacy in various angiogenesis-dependent disorders, including solid tumors, psoriasis, rheumatoid arthritis and diabetic retinopathy.
Oikawa
T
T
Division of Cancer Therapeutics, Tokyo Metropolitan Institute of Medical Science, Japan.
Okayasu
I
I
Ashino
H
H
Morita
I
I
Murota
S
S
Shudo
K
K
D000818:Animals; D001565:Benzoates / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology* / Q000627:therapeutic use
D001565:Benzoates; D013764:Tetrahydronaphthalenes; C061133:tamibarotene; C068073:Am 580; C085268:Re 80