(a) Structure
and key properties of compound 28. (b,c)
Selectivity profile of 3 and optimized derivative 28 on 12 nuclear receptors related to RXRs at 30 μM.
Although 3 also activates RAR, 28 gained
full RXR selectivity. n ≥ 3. (d, e) 28 activated permissive RXR heterodimers with (d) PPAR and
(e) LXR in full-length assays showing synergistic effects with the
respective partner agonists rosiglitazone (Rosi) and T0901317 (T090);
(d) n = 3, (e) n = 4. (f) 28 induced RXR-regulated gene expression (qRT-PCR) of adiponectin
(ADIPOQ), angiopoietin-like 4 (ANGPTL4), and apolipoprotein E (APOE)
with similar efficacy as bexarotene (1, Bex). n =
4. All values are mean ± SEM; ∗ p <
0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001.