4-[3-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)phenyl]benzoic acid and heterocyclic-bridged analogues are novel retinoic acid receptor subtype and retinoid X receptor alpha agonists.
Aromatic retinoids having a meta-substituted aromatic ring bridge, such as 4-[3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)phenyl]benzo ic acid and its 3,5-diaryl-substituted 4,5-dihydroisoxazole analogue, function as retinoid receptor panagonists by activating both retinoic acid and retinoid X receptors to induce gene transcription, and thereby provide novel scaffolds for retinoid drug development. Both classes of these ligand-inducible transcription factors are involved in mediating the inhibitory effects of retinoids on cancer cell growth.
Dawson
M I
MI
Medicinal Chemistry Department, Molecular Medicine Research Institute, Mountain View, CA 94043, USA. mdawson@mmrx.org
Jong
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L
Hobbs
P D
PD
Xiao
D
D
Feng
K C
KC
Chao
W R
WR
Pan
C
C
Fontana
J A
JA
Zhang
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XK
D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology*; D018168:Receptors, Retinoic Acid / Q000819:agonists*; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000819:agonists*; D014407:Tumor Cells, Cultured
C415643:4-(3-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)phenyl)benzoic acid; D001565:Benzoates; D006571:Heterocyclic Compounds; D009281:Naphthalenes; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors