Description
LE 135 is a retinoic acid receptor (RAR) antagonist that displays moderate selectivity for RARβ over RARα (Kis = 0.22 and 1.4 μM, respectively). LE 135 inhibits retinoic acid-induced transcriptional activation of RARβ (>70% inhibition at 10 μM), but not RARα, RARγ or retinoid X receptor α. It has been shown to inhibit retinoid Am80-induced differentiation of human promyelocytic leukemia cells, HL-60, with an IC50 value of 0.2 μM.
Uses
LE 135 has been used for in vitro islet treatment.
Definition
ChEBI: 4-(5,7,7,10,10-pentamethyl-8,9-dihydronaphtho[2,3-b][1,4]benzodiazepin-13-yl)benzoic acid is a dibenzodiazepine.
Biological Activity
Retinoic acid antagonist; displays moderate selectivity for RAR β over RAR α (K i 爒alues are 0.22 and 1.4 μ M respectively). Highly selective over RAR γ and RXR α . Inhibits human HL-60 leukemia cell differentiation induced by Am80 (IC 50 = 150 nM).
Biochem/physiol Actions
LE135 is a retinoic acid receptor (RAR) antagonist with selectivity for RARβ (Ki = 220 nM) over RARα (Ki = 1.4 μM). LE135 inhibits retinoic acid-induced transcriptional activation of RARβ (>70% inhibition at 10 μM), but not RARα, RARγ or retinoid X receptor α (RXRα). There is high interest in retinoic acid receptors for cancer and for differentiation studies. LE135 has been shown to inhibit retinoid Am80-induced differentiation of human promyelocytic leukemia HL-60 cells with an IC50 value of 0.2 μM. LE135 has been used to study the role of a retinoic acid receptor-β (RARβ) on the differentiation of mesenchymal stem cells, and was found to inhibit the neuronal differentiation promoting effects of all-trans retinoic acid (ATRA) on mesenchymal stem cells.
