| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg |
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| Other Sizes |
| Targets |
LE135 targets retinoic acid receptors (RARs), specifically RARα and RARβ, acting as a potent antagonist. It binds selectively to RARα (Ki = 1.4 μM) and RARβ (Ki = 220 nM), with higher affinity for RARβ. The compound is selective for RARα and RARβ over RARγ, RXRα, RXRβ, and RXRγ. LE135 also functions as a potent activator of TRPV1 and TRPA1 receptors, with EC₅₀ values of 2.5 μM and 20 μM, respectively. By antagonizing RARs, LE135 blocks retinoic acid-induced transactivation, making it a valuable tool for dissecting RARβ's distinct biological roles.
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| ln Vitro |
LE135 suppresses the differentiation of human promyelocytic leukemia cells HL-60 caused by Am80 with an IC50 of 150 nM[1]. On several RA response elements, LE135 blocks retinoic acid (RA)-induced transactivation of RARβ but not that of RARα, RARγ, or retinoid X receptor α (RXRα). LE135 significantly suppresses 12-O-tetradecanoylphorbol-13-acetate-induced AP-1 activity when RARβ and RXRα are present [3].
In vitro, LE135 suppresses the differentiation of human promyelocytic leukemia HL-60 cells caused by Am80 with an IC₅₀ of 150 nM. On several retinoic acid response elements (RAREs), LE135 blocks retinoic acid-induced transactivation of RARβ but not that of RARα, RARγ, or RXRα. The compound significantly suppresses 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced AP-1 activity when RARβ and RXRα are present. These in vitro activities confirm its role as a selective RARβ antagonist. |
| ln Vivo |
LE135 produces thermal hyperalgesia and nociceptive responses mostly through TRPV1 channels; however, mechanical allodynia cannot be produced without TRPA1 and TRPV1 channels. In both wild-type and Trpa1−/− mice, an intraplantar injection of LE135 (30 nmol/10 μL) results in mechanical hypersensitivity [2].
In vivo, LE135 produces thermal hyperalgesia and nociceptive responses mostly through TRPV1 channels; however, mechanical allodynia requires both TRPA1 and TRPV1 channels. In both wild-type and Trpa1⁻/⁻ mice, an intraplantar injection of LE135 (30 nmol/10 μL) results in mechanical hypersensitivity. These in vivo activities confirm its role as a TRPV1 and TRPA1 activator in pain pathways. Detailed in vivo data on its RAR antagonism are not extensively reported. |
| Enzyme Assay |
Non-cell-based receptor binding assays for LE135 typically involve radioligand binding studies using purified RARα, RARβ, and RARγ proteins. The receptor is incubated with a radiolabeled retinoic acid ligand (e.g., [³H]-ATRA) and varying concentrations of LE135. Binding affinity (Ki) is determined by measuring displacement of the radiolabeled ligand. TRPV1 and TRPA1 receptor activation can be assessed using calcium flux assays in cell-free membrane preparations or using fluorescent calcium indicators.
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| Cell Assay |
Cellular assays for LE135 are performed using HL-60 cells to assess inhibition of Am80-induced differentiation. Cells are treated with the compound at various concentrations, and differentiation markers are measured. Reporter gene assays are used to assess RAR transactivation: cells are transfected with RAREs driving luciferase expression and treated with LE135 in the presence or absence of retinoic acid. TRPV1 and TRPA1 activation is assessed in cells expressing these channels by measuring intracellular calcium levels using fluorescence-based assays.
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| Animal Protocol |
In vivo animal models for LE135 include studies in wild-type and Trpa1⁻/⁻ mice to assess pain responses. The compound is administered via intraplantar injection at 30 nmol/10 μL. Thermal hyperalgesia, nociceptive responses, and mechanical allodynia are measured using standard pain behavior assays such as the hot plate test, von Frey filaments, and paw withdrawal thresholds. These studies confirm the compound's role in TRPV1 and TRPA1-mediated pain pathways.
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| ADME/Pharmacokinetics |
LE135 has a molecular weight of 438.57 g/mol and a molecular formula of C₂₉H₃₀N₂O₂. CAS number is 155877-83-1. The compound is a yellow to brown solid powder. Purity is ≥98%. It is soluble in DMSO. LogP is 7.36. Boiling point is 601.3°C. Storage conditions: powder at -20°C. The compound is supplied for research use only.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for LE135 are not extensively reported in the available literature. As a research compound, its safety profile would need to be established through standard preclinical toxicity assessments. The compound is supplied for research use only and is not for human consumption. Given its activity as a TRPV1 and TRPA1 activator, potential effects on pain pathways and sensory neurons would be key safety considerations. Standard laboratory safety precautions should be followed.
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| References |
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| Additional Infomation |
4-(5,7,7,10,10-pentamethyl-8,9-dihydronaphtho[2,3-b][1,4]benzodiazepine-13-yl)benzoic acid is a dibenzodiazepine.
LE135 is also known as LE-135 and LE 135. It is a potent RAR antagonist that selectively binds RARα (Ki = 1.4 μM) and RARβ (Ki = 220 nM), with higher affinity for RARβ. It is selective for RARα and RARβ over RARγ, RXRα, RXRβ, and RXRγ. LE135 is also a potent activator of TRPV1 (EC₅₀ = 2.5 μM) and TRPA1 (EC₅₀ = 20 μM) receptors. It is widely used in cancer biology, developmental biology, and dermatology research. The compound is for research use only. |
| Molecular Formula |
C29H30N2O2
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| Molecular Weight |
438.57
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| Exact Mass |
438.23
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| CAS # |
155877-83-1
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| PubChem CID |
10410894
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| Appearance |
Yellow to brown solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
601.3±55.0 °C at 760 mmHg
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| Flash Point |
317.5±31.5 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.628
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| LogP |
7.36
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
33
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| Complexity |
779
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
YZZAIQOVMHVWBS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H30N2O2/c1-28(2)14-15-29(3,4)22-17-25-23(16-21(22)28)30-26(18-10-12-19(13-11-18)27(32)33)20-8-6-7-9-24(20)31(25)5/h6-13,16-17H,14-15H2,1-5H3,(H,32,33)
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| Chemical Name |
4-(5,7,7,10,10-pentamethyl-8,9-dihydronaphtho[2,3-b][1,4]benzodiazepin-13-yl)benzoic acid
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| Synonyms |
LE-135; LE 135; LE135
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~114.01 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.70 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.70 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2801 mL | 11.4007 mL | 22.8014 mL | |
| 5 mM | 0.4560 mL | 2.2801 mL | 4.5603 mL | |
| 10 mM | 0.2280 mL | 1.1401 mL | 2.2801 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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