| Description | LE135 is a potent RAR antagonist that binds selectively to RARα (Ki of 1.4 μM) and RARβ (Ki of 220 nM), and has a higher affinity to RARβ. LE135 is highly selective over RARγ, RXRα, RXRβ and RXRγ. LE135 is also a potent TRPV1 and TRPA1 receptors activator with EC50s of 2.5 μM and 20 μM, respectively. |
| In vitro | LE135 inhibits Am80-induced differentiation of human promyelocytic leukemia cells HL-60 with an IC50 of 150 nM[1]. LE135 inhibits retinoic acid (RA)-induced transcriptional activation of RARβ, but not RARα, RARγ or retinoid X receptor α (RXRα), on a variety of RA response elements. LE135 strongly represses 12-O-tetradecanoylphorbol-13-acetate-induced AP-1 activity in the presence of RARβ and RXRα[3]. |
| In vivo | LE135通过TRPV1通道主要引发痛觉反应并诱发热性痛觉过敏，但产生机械性痛觉过敏需要TRPA1和TRPV1两种通道。在野生型和Trpa1−/−小鼠中，足底注射LE135（30 nmol/10 μL）会诱导机械性过敏[2]。 |
| Target activity | RARβ:220 nM (Ki), TRPV1:2.5 μM (EC50), TRPA1:20 μM (EC50), RARα:1400 nM (Ki) |
| Synonyms | LE 135 |
| molecular weight | 438.56 |
| Molecular formula | C29H30N2O2 |
| CAS | 155877-83-1 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 45 mg/mL (102.6 mM), Sonication is recommended. |
| References | 1. H Umemiya, et al. Regulation of retinoidal actions by diazepinylbenzoic acids. Retinoid synergists which activate the RXR-RAR heterodimers. J Med Chem. 1997 Dec 19;40(26):4222-34. 2. Shijin Yin, et al. LE135, a retinoid acid receptor antagonist, produces pain through direct activation of TRP channels. Br J Pharmacol. 2014 Mar;171(6):1510-20. 3. Y Li, et al. Identification of a novel class of retinoic acid receptor beta-selective retinoid antagonists and their inhibitory effects on AP-1 activity and retinoic acid-induced apoptosis in human breast cancer cells. J Biol Chem. 1999 May 28;274(22):15 |