Communications to the Editor
J ournal of Medicinal Chemistry, 1996, Vol. 39, No. 17 3233
function as a versatile biological tool to dissect RXR-
dependent transcriptional activities. The evidence that
LG100754 (2) functions as an antagonist suggests that
this unique ligand interacts with the RXR ligand
Receptors. Cell 1989, 57, 1139-1146. (c) Umesono, K.; Mu-
rakami, K. K.; Thompson, C. C.; Evans, R. M. Direct Repeats
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Retinoic Acid, and Vitamin D3 Receptors. Cell 1991, 65, 1255-
1
266. (d) Yang, N.; Schule, R.; Mangelsdorf, D. J .; Evans, R. M.
Characterization of DNA Binding and Retinoic Acid Binding
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2
3
binding domain but may somehow inactivate or fail
to induce the AF-2 activation domain, possibly because
of the increased bulk of the 3-propoxy substituent.
Thus, LG100754 (2) may prevent the optimal structural
changes necessary for activating transcription. Other
transcriptional responses have been investigated with
LG100754 (2) and RXR heterodimers, and some selec-
tive interactions with certain cofactors and basal tran-
scriptional proteins have been observed.24 As is the case
for anti-estrogen and anti-androgen hormones, RXR
antagonists, such as LG100754 (2), could help define
the specific transcriptional activities necessary for
receptor activation and hormone signaling.
(
7) (a) Yu, V. C.; Delsert, C.; Andersen, B.; Holloway, J . M.; Devary,
O. V.; N a¨ a¨ r, A. M.; Kim, S. Y.; Boutin, J .-M.; Glass, C. K.;
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Ack n ow led gm en t. The authors wish to thank Y.
L. Bennani for helpful synthetic discussions.
1
992, 358, 587-591. (d) Isseman, I.; Prince, R. A.; Tugwood, J .
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Ordering information is given on any current masthead page.
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Direct Repeats. Nature 1995, 375, 203-211. (h) Forman, B. M.;
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