LE135 is a potent RAR antagonist that binds selectively to RARα (K_i of 1.4 μM) and RARβ (K_i 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].

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

438.56

C₂₉H₃₀N₂O₂

155877-83-1

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : 66.67 mg/mL (152.02 mM; Need ultrasonic)

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (5.70 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.70 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: 2.5 mg/mL (5.70 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (5.70 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明

• [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.