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PDBsum entry 4m8h
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Transcription
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PDB id
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4m8h
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References listed in PDB file
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Key reference
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Title
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Methyl-Substituted conformationally constrained rexinoid agonists for the retinoid x receptors demonstrate improved efficacy for cancer therapy and prevention.
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Authors
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A.Desphande,
G.Xia,
L.J.Boerma,
K.K.Vines,
V.R.Atigadda,
S.Lobo-Ruppert,
C.J.Grubbs,
F.L.Moeinpour,
C.D.Smith,
K.Christov,
W.J.Brouillette,
D.D.Muccio.
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Ref.
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Bioorg Med Chem Lett, 2014,
22,
178-185.
[DOI no: ]
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PubMed id
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Abstract
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(2E,4E,6Z,8Z)-8-(3',4'-Dihydro-1'(2H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,3,6-octatrienoinic
acid, 9cUAB30, is a selective rexinoid for the retinoid X nuclear receptors
(RXR). 9cUAB30 displays substantial chemopreventive capacity with little
toxicity and is being translated to the clinic as a novel cancer prevention
agent. To improve on the potency of 9cUAB30, we synthesized 4-methyl analogs of
9cUAB30, which introduced chirality at the 4-position of the tetralone ring. The
syntheses and biological evaluations of the racemic homolog and enantiomers are
reported. We demonstrate that the S-enantiomer is the most potent and least
toxic even though these enantiomers bind in a similar conformation in the ligand
binding domain of RXR.
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