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.