LE 135

Names

[ Name ]:
LE 135

[Synonym ]:
4-(5,7,7,10,10-Pentamethyl-7,8,9,10-tetrahydro-5H-benzo[e]naphtho[2,3-b][1,4]diazepin-13-yl)benzoic acid
hms3268h07
Benzoic acid, 4-(7,8,9,10-tetrahydro-5,7,7,10,10-pentamethyl-5H-benzo[e]naphtho[2,3-b][1,4]diazepin-13-yl)-
le 135

Biological Activity

[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[1][2].

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> TRP Channel

Research Areas >> Cancer

Research Areas >> Neurological Disease

Signaling Pathways >> Metabolic Enzyme/Protease >> RAR/RXR

[Target]

RARβ:220 nM (Ki)

RARα:1400 nM (Ki)

TRPV1:2.5 μM (EC50)

TRPA1:20 μM (EC50)

[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 provokes nociceptive responses and elicited thermal hyperalgesia mainly through TRPV1 channels, but required both TRPA1 and TRPV1 channels for producing mechanical allodynia. Intraplantar injection of LE135 (30 nmol/10 μL) induces mechanical hypersensitivity in wild-type and Trpa1−/− mice[2].

[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):15360-6.

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
601.3±55.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₉H₃₀N₂O₂

[ Molecular Weight ]:
438.561

[ Flash Point ]:
317.5±31.5 °C

[ Exact Mass ]:
438.230713

[ PSA ]:
52.90000

[ LogP ]:
7.36

[ Vapour Pressure ]:
0.0±1.8 mmHg at 25°C

[ Index of Refraction ]:
1.628

[ Storage condition ]:
2-8°C

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319

[ Precautionary Statements ]:
P305 + P351 + P338

[ Hazard Codes ]:
Xi

[ RIDADR ]:
NONH for all modes of transport