| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
Heclin targets HECT E3 ubiquitin ligases, specifically Smurf2, Nedd4, and WWP1. The IC₅₀ values are 6.8 μM for Smurf2, 6.3 μM for Nedd4, and 6.9 μM for WWP1. By inhibiting these E3 ligases, Heclin prevents the ubiquitination and degradation of their substrate proteins, modulating downstream signaling pathways including the IGF1 signaling pathway.
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|---|---|
| ln Vitro |
Heclin (10 μM, 1–5 days) affects the IGF1 signaling pathway and the viability of BGC803 and MKN45 cells [1]. In Raw264.7 cells, heclin (7 μM, 1 h) enhances epinecidin-1-mediated MyD88 degradation [2].
In vitro, Heclin inhibits several HECT ligases in cultured cells with IC₅₀ values of 6.8, 6.3, and 6.9 μM for Smurf2, Nedd4, and WWP1, respectively. In BGC803 and MKN45 gastric cancer cells, Heclin (10 μM, 48 hours) decreases phosphorylation of Akt, affecting the IGF1 signaling pathway and cell viability. In Raw264.7 cells, Heclin (7 μM, 1 hour) enhances epinecidin-1-mediated MyD88 degradation. |
| ln Vivo |
In vivo studies on Heclin are limited. As an inhibitor of HECT E3 ubiquitin ligases with effects on gastric cancer cell viability, it would be expected to be evaluated in animal models of gastric cancer. The compound's effects on tumor growth, apoptosis, and signaling pathways would be assessed in xenograft models.
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| Enzyme Assay |
Cell-free enzyme assays for Heclin involve measuring its inhibition of HECT E3 ubiquitin ligase activity. These assays typically use purified HECT domains of Smurf2, Nedd4, or WWP1, along with E1 and E2 ubiquitin-conjugating enzymes, ubiquitin, and a substrate protein. The reaction is incubated with various concentrations of Heclin, and the ubiquitination of the substrate is detected by Western blot or by using radiolabeled ubiquitin. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: BGC803 and MKN45 cells Tested Concentrations: 10 μM Incubation Duration: 48 h Experimental Results: decreased phosphorylation of Akt. In vitro cellular assays for Heclin use various cell types, including gastric cancer cell lines BGC803 and MKN45. Cells are treated with Heclin (10 μM) for 48 hours, and cell viability is measured using MTT or CCK-8 assays. The effects on signaling pathways are assessed by Western blot, including measurement of phosphorylated Akt. In Raw264.7 cells, Heclin (7 μM, 1 hour) is used to study MyD88 degradation. |
| Animal Protocol |
In vivo animal studies for Heclin would typically use mouse xenograft models of gastric cancer. Immunodeficient mice are inoculated with gastric cancer cells, and when tumors reach a certain size, animals are randomized to receive Heclin or vehicle control. The compound is administered via intraperitoneal injection. Tumor growth is monitored by caliper measurements. At the end of the study, tumors are collected for analysis of signaling pathways and apoptosis.
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| ADME/Pharmacokinetics |
Heclin has a molecular formula of C₁₇H₁₇NO₃ and a molecular weight of 283.32. It is soluble in DMSO (~100 mg/mL). The compound should be stored as a powder at -20°C for 3 years and in solution at -80°C for 6 months. It is stable at room temperature for a few days during shipping. For in vivo studies, it can be formulated in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% saline.
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| Toxicity/Toxicokinetics |
Heclin is the first small molecule inhibitor of HECT domain-containing E3 ubiquitin ligases. It inhibits Smurf2, Nedd4, and WWP1 with IC₅₀ values of 6.8, 6.3, and 6.9 μM, respectively. Heclin affects the IGF1 signaling pathway and the viability of gastric cancer cells and may be utilized in gastric cancer research. Heclin is for research use only and not for human therapeutic use.
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| References |
[1]. Mund T, et al. Peptide and small molecule inhibitors of HECT-type ubiquitin ligases. Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16736-41.
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| Molecular Formula |
C17H17NO3
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|---|---|
| Molecular Weight |
283.321784734726
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| Exact Mass |
283.12
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| CAS # |
890605-54-6
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| PubChem CID |
7464118
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| Appearance |
Off-white to light brown solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
495.4±45.0 °C at 760 mmHg
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| Flash Point |
253.4±28.7 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.615
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| LogP |
4.22
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
21
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| Complexity |
397
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCC1=CC=C(O1)/C=C/C(=O)NC2=CC=C(C=C2)C(=O)C
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| InChi Key |
SPTWXRJNCFIDRQ-ZHACJKMWSA-N
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| InChi Code |
InChI=1S/C17H17NO3/c1-3-15-8-9-16(21-15)10-11-17(20)18-14-6-4-13(5-7-14)12(2)19/h4-11H,3H2,1-2H3,(H,18,20)/b11-10+
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| Chemical Name |
(E)-N-(4-acetylphenyl)-3-(5-ethylfuran-2-yl)prop-2-enamide
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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 (~352.96 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.82 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 (8.82 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5296 mL | 17.6479 mL | 35.2958 mL | |
| 5 mM | 0.7059 mL | 3.5296 mL | 7.0592 mL | |
| 10 mM | 0.3530 mL | 1.7648 mL | 3.5296 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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