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| 5mg |
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| 10mg |
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| Targets |
HECT E3 ligases (specifically Nedd4-1). HECT E3-IN-1 is an inhibitor of HECT E3 ligases. It acts by disrupting ubiquitin (Ub) binding at the non-covalent Ub-binding site of Nedd4-1. By blocking this binding, it prevents the transfer of ubiquitin from the E2 enzyme to the substrate.
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| ln Vitro |
HECT E3-IN-1 (compound 3) is a HECT E3 ligase inhibitor that disrupts ubiquitin (Ub) binding to the non-covalent Ub-binding site of Nedd4-1. By blocking this interaction, it prevents the transfer of ubiquitin from the E2 enzyme to the substrate, thereby inhibiting the ubiquitination of target proteins. The IC50 and Ki for HECT E3-IN-1 are not detailed in the supplier literature.
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| ln Vivo |
In vivo activity data for HECT E3-IN-1 are not detailed in the available literature. As an inhibitor of HECT E3 ligases, it has potential applications in studying diseases where these ligases are dysregulated, such as in certain cancers (e.g., where Nedd4-1 is involved) and in neurological disorders. Further in vivo studies would be required to characterize its efficacy, pharmacokinetics, and safety profile.
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| Enzyme Assay |
For non-cellular assays, the binding of ubiquitin (Ub) to Nedd4-1 is measured using a fluorescence polarization (FP) or a TR-FRET assay. A labeled ubiquitin is incubated with the Nedd4-1 protein. HECT E3-IN-1 is added at varying concentrations (0.1-100 uM). A decrease in polarization or FRET signal indicates disruption of the Ub-Nedd4-1 interaction. The IC50 for inhibition is calculated from the dose-response curve.
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| Cell Assay |
Cellular assays involve treating cancer cell lines (e.g., HeLa, HEK293T) with HECT E3-IN-1 (5-100 uM) for 6-24 hours. The total levels of ubiquitinated proteins are assessed by Western blotting with an anti-ubiquitin antibody. A decrease in the overall ubiquitination signal, or specifically in the ubiquitination of known Nedd4-1 substrates (e.g., ENaC, PTEN), would indicate on-target activity. Cell viability is also assessed by MTT assay.
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| Animal Protocol |
HECT E3-IN-1 can be formulated in a vehicle such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline for intraperitoneal injection in animal models. A typical study might involve administering the compound to mice bearing subcutaneous xenografts. Tumor volume is measured, and tumor lysates are analyzed for ubiquitination levels and for the expression levels of proteins known to be regulated by Nedd4-1. Body weight would be monitored as a marker of toxicity.
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| ADME/Pharmacokinetics |
HECT E3-IN-1 has a molecular formula of C21H26N2O4 and a molecular weight of 370.44 g/mol. It is a small molecule with a relatively high logP (indicating lipophilicity). The compound is soluble in DMSO (≥10 mg/mL). It is typically stored as a solid at -20degC, protected from light and moisture. Detailed pharmacokinetic parameters (half-life, oral bioavailability) are not reported in the supplier literature.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for HECT E3-IN-1 are not available. It is intended for research use only and not for human consumption. Standard safety precautions for handling research chemicals should be followed, including the use of gloves and eye protection. As an inhibitor of a key enzyme family in the protein degradation pathway, off-target effects on normal cellular protein turnover could potentially cause toxicity.
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| References | |
| Additional Infomation |
HECT E3-IN-1 (compound 3) is a research-grade chemical, not an FDA-approved drug. It is a tool compound used to study the function of HECT E3 ligases, particularly Nedd4-1. Nedd4-1 is involved in the regulation of the epithelial sodium channel (ENaC), PTEN tumor suppressor, and growth factor receptors. By inhibiting Nedd4-1, this compound could be used to study ion channel regulation, cancer cell survival, and protein trafficking pathways.
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| Molecular Formula |
C21H26N2O4
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|---|---|
| Molecular Weight |
370.442145824432
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| Exact Mass |
370.189
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| CAS # |
1810058-52-6
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| PubChem CID |
91844662
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| Appearance |
White to off-white solid powder
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| LogP |
3
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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 |
7
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| Heavy Atom Count |
27
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| Complexity |
558
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(OC)(=O)/C=C/CNC(C1C2=C(N(C3CCCC3)C=1C)C=CC(OC)=C2)=O
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| InChi Key |
ONZCVJIBENGLKN-RMKNXTFCSA-N
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| InChi Code |
InChI=1S/C21H26N2O4/c1-14-20(21(25)22-12-6-9-19(24)27-3)17-13-16(26-2)10-11-18(17)23(14)15-7-4-5-8-15/h6,9-11,13,15H,4-5,7-8,12H2,1-3H3,(H,22,25)/b9-6+
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| Chemical Name |
methyl (E)-4-[(1-cyclopentyl-5-methoxy-2-methylindole-3-carbonyl)amino]but-2-enoate
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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: 100 mg/mL (269.95 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.75 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 (6.75 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.75 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6995 mL | 13.4975 mL | 26.9949 mL | |
| 5 mM | 0.5399 mL | 2.6995 mL | 5.3990 mL | |
| 10 mM | 0.2699 mL | 1.3497 mL | 2.6995 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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