| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| 250mg |
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| Targets |
LDN-91946 targets ubiquitin C-terminal hydrolase-L1 (UCH-L1), a deubiquitinating enzyme (DUB) that plays a critical role in the ubiquitin-proteasome system. UCH-L1 is involved in the removal of ubiquitin from protein substrates, regulating protein degradation and cellular homeostasis. The compound acts as an uncompetitive inhibitor, meaning it binds to the enzyme-substrate complex rather than the free enzyme. UCH-L1 is overexpressed in various cancers and is associated with poor prognosis, making it a potential therapeutic target. By inhibiting UCH-L1, LDN-91946 disrupts the ubiquitin-proteasome pathway and may induce apoptosis in cancer cells.
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| ln Vitro |
At 20 μM, LDN-91946 has no effect on UCH-L3. At 40 μM, LDN-91946 exhibits no activity against papain, caspase-3, or TGase 2 [1]. Treatment of serum-starved Neuro 2A (N2A) cells with concentrations up to 0.1 mM of LDN-91946 does not result in cytotoxicity [1].
In vitro, LDN-91946 inhibits UCH-L1 with an apparent Ki of 2.8 μM. At 20 μM, the compound has no effect on UCH-L3. At 40 μM, LDN-91946 exhibits no activity against papain, caspase-3, or TGase 2. Treatment of serum-starved Neuro 2A (N2A) cells with concentrations up to 0.1 mM of LDN-91946 does not result in cytotoxicity. These in vitro activities confirm its selectivity for UCH-L1 over other proteases and deubiquitinating enzymes, as well as its low cellular toxicity. |
| ln Vivo |
Detailed in vivo activity data for LDN-91946 are not extensively reported in the available literature. As a potent and selective UCH-L1 inhibitor with potential anticancer activity, it is expected to have applications in cancer research. The compound's ability to inhibit UCH-L1 without affecting other proteases suggests a favorable selectivity profile for in vivo studies. However, specific in vivo efficacy data from animal models are not provided in the available sources.
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| Enzyme Assay |
Non-cell-based enzyme assays for LDN-91946 typically involve in vitro UCH-L1 activity assays using purified recombinant UCH-L1 enzyme. The compound is incubated with the enzyme and a fluorogenic substrate (e.g., ubiquitin-AMC) at varying concentrations. UCH-L1 activity is measured by monitoring the release of free AMC (7-amino-4-methylcoumarin) using fluorescence spectroscopy. The apparent Ki is determined from dose-response curves using appropriate kinetic models. Selectivity profiling against UCH-L3, papain, caspase-3, and TGase 2 is performed to confirm specificity.
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| Cell Assay |
Cellular assays for LDN-91946 are performed using Neuro 2A (N2A) cells to assess cytotoxicity. Cells are treated with the compound at concentrations up to 0.1 mM, and cell viability is measured using standard assays such as MTT or LDH release. For mechanistic studies, cells are treated with the compound, and ubiquitin-proteasome pathway activity is assessed by measuring ubiquitinated protein levels via Western blotting. Apoptosis markers such as caspase-3 activation and PARP cleavage may also be evaluated.
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| Animal Protocol |
In vivo animal models for LDN-91946 would be required to assess its therapeutic potential. Based on its mechanism as a UCH-L1 inhibitor with anticancer activity, relevant models could include xenograft studies in immunodeficient mice bearing cancer cell lines. The compound would be administered via appropriate routes (e.g., oral gavage or intraperitoneal injection) at various doses. Tumor growth inhibition would be monitored over time. Pharmacodynamic markers such as ubiquitinated protein levels in tumor tissues would be assessed. Detailed protocols are not extensively reported.
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| ADME/Pharmacokinetics |
LDN-91946 has a molecular weight of 314.32 g/mol and a molecular formula of C₁₅H₁₀N₂O₄S. CAS number is 439946-22-2. The compound is soluble in DMSO at 83 mg/mL. Purity is typically ≥97% by HPLC. Appearance is a white solid powder. Storage conditions: powder at -20°C for 3 years; in solvent at -80°C for 1 year. The compound is supplied for research use only.
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| Toxicity/Toxicokinetics |
LDN-91946 shows no cytotoxicity in Neuro 2A cells at concentrations up to 0.1 mM. It has no activity against papain, caspase-3, or TGase 2 at 40 μM. Detailed toxicological data are not extensively reported. As a research compound, its full 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. Standard laboratory safety precautions should be followed.
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| References | |
| Additional Infomation |
LDN-91946 is a potent, selective, and uncompetitive inhibitor of ubiquitin C-terminal hydrolase-L1 (UCH-L1) with a Ki app of 2.8 μM. It has a molecular weight of 314.32 g/mol and a molecular formula of C₁₅H₁₀N₂O₄S. The compound shows selectivity for UCH-L1 over UCH-L3, papain, caspase-3, and TGase 2. It has potential anticancer activity. LDN-91946 is a small-molecule triazine derivative used in research applications studying the ubiquitin-proteasome system and deubiquitinating enzymes. It is for research use only.
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| Molecular Formula |
C₁₅H₁₀N₂O₄S
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|---|---|
| Molecular Weight |
314.32
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| Exact Mass |
314.036
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| CAS # |
439946-22-2
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| PubChem CID |
950368
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| Appearance |
Light brown to brown solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
714.0±60.0 °C at 760 mmHg
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| Flash Point |
385.6±32.9 °C
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| Vapour Pressure |
0.0±2.4 mmHg at 25°C
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| Index of Refraction |
1.722
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| LogP |
2.2
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
22
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| Complexity |
542
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
OJHMDRZMENMQFP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H10N2O4S/c16-10-8-6-9(15(20)21)13(19)17-14(8)22-12(10)11(18)7-4-2-1-3-5-7/h1-6H,16H2,(H,17,19)(H,20,21)
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| Chemical Name |
3-amino-2-benzoyl-6-oxo-6H,7H-thieno[2,3-b]pyridine-5-carboxylic acid
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| Synonyms |
LDN91946 LDN 91946 LDN-91946
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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 : ~83.33 mg/mL (~265.11 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1815 mL | 15.9074 mL | 31.8147 mL | |
| 5 mM | 0.6363 mL | 3.1815 mL | 6.3629 mL | |
| 10 mM | 0.3181 mL | 1.5907 mL | 3.1815 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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