Methyl-substituted conformationally constrained rexinoid agonists for the retinoid X receptors demonstrate improved efficacy for cancer therapy and prevention

Academic Article

Abstract

  • (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. © 2013 Published by Elsevier Ltd. All rights reserved.
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    Author List

  • Desphande A; Xia G; Boerma LJ; Vines KK; Atigadda VR; Lobo-Ruppert S; Grubbs CJ; Moeinpour FL; Smith CD; Christov K
  • Start Page

  • 178
  • End Page

  • 185
  • Volume

  • 22
  • Issue

  • 1