In Vitro: Bexarotene?selectively binds and activates RXR subtypes with Kd=14±2 nM, 21±4 nM, and 29±7 nM for RXRα, RXRβ, and RXRγ subtypes.? Bexarotene?is effective in limiting the proliferation of leukemic (HL-60) cells.?Bexarotene inhibits the proliferation of HL-60 cells by 37% at 1 μM.?? Bexarotene monotherapy of cells shows an antiproliferative effect at a high dose, and the IC50s aere 40.62±0.45?μM (PC3) and 50.20±4.10?μM (DU145).?? Bexarotene (20 and 40 μM) and Docetaxel (5 and 10 μM) exhibit a synergistic effect on the inhibition of PC3 and DU145 cell proliferation. Bexarotene (20 and 40?μM) represses cyclin D1 and cyclin D3 expression in PC3 and DU145 cells.
In Vivo: Bexarotene??(1 mg/kg/day) is effective in blocking the development of behavioral deficits and dopamine neuron degeneration in a rat model of Parkinson’s disease (PD) producing significantly reduced changes in both triglycerides and T4 serum.? Bexarotene is an effective preventive agent against lung tumor growth and progression. Bexarotene (100?mg/kg by gavage) inhibits both tumor multiplicity and tumor volume in mice of all three genotypes (p53wt/wtK-raswt/wt, p53val135/wtK-raswt/wt, or p53wt/wtK-rasko/wt). Bexarotene reduces the progression of adenoma to adenocarcinoma by?~50% in both p53wt/wtK-rasko/wt?and p53wt/wtK-raswt/wt?mice.