V. Vuligonda et al., A new class of RAR subtype selective retinoids: Correlation of pharmacological effects with receptor activity, BIO MED CH, 7(2), 1999, pp. 263-270
The synthesis and biological activity of a series of structurally related r
etinoids with different RAR subtype selectivities are described. These reti
noids bind to all three RAR subtypes but in functional transactivation assa
ys, they show RAR beta or RAR beta,gamma selectivity with weak RAR alpha ac
tivity. The subtype selectivity of these retinoids was found to correlate w
ith their efficacy (ODC inhibition) and toxicity (topical irritation and te
ratogenicity) profiles. The degree of RAR gamma transactivation activity co
rrelates with their topical toxicity and teratogenicity as measured by the
inhibition of chondrogenesis. Of the RAR beta selective retinoids reported
here, retinoid 12 is the most promising, as it is completely devoid of two
common retinoid related toxicities, namely topical irritation and teratogen
esis. (C) 1999 Elsevier Science Ltd. All rights reserved.