A NEW CLASS OF RETINOIDS WITH SELECTIVE-INHIBITION OF AP-1 INHIBITS PROLIFERATION

RETINOIDS regulate many biological processes, including differentiatio n, morphogenesis and cell proliferation(1-3). They are also important therapeutic agents, but their clinical usefulness is limited because o f side effects(4-8). Retinoid activities are mediated by specific nucl ear receptors, the RARs and RXRs, which can induce transcriptional act ivation through specific DNA sites(3,9-11) or by inhibiting the transc ription factor AP-1 (refs 12-15), which usually mediates cell prolifer ation signals(16). Because the two types of receptor actions are mecha nistically distinct(12,15) we investigated whether conformationally re stricted retinoids, selective for each type of receptor action, could be identified, Here we describe a new class of retinoids that selectiv ely inhibits AP-1 activity but does not activate transcription. These retinoids do not induce differentiation in F9 cells but inhibit effect ively the proliferation of several tumour cell lines, and could thus s erve as candidates for new retinoid therapeutic agents with reduced si de effects.