| Size | Price | Stock | Qty |
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| 100mg |
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| 500mg |
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| 1g |
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| Other Sizes |
| Targets |
E28362 targets proprotein convertase subtilisin/kexin type 9 (PCSK9). It acts as an antagonist that blocks the interaction between PCSK9 and the low-density lipoprotein receptor (LDLR). By inhibiting this binding, E28362 prevents the endosomal degradation of LDLR, thereby increasing LDLR levels on the cell surface and promoting the clearance of LDL-cholesterol from the circulation.
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| ln Vitro |
In vitro studies demonstrate that E28362 is not cytotoxic even at high concentrations, suggesting a favorable safety profile. Treatment with E28362 significantly elevates both cell surface and total LDLR protein levels, which consequently enhances the cellular uptake of low-density lipoprotein (LDL). This activity supports its role in maintaining cholesterol homeostasis within cells and is a key component of its mechanism as a lipid-lowering agent.
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| ln Vivo |
As a small-molecule PCSK9 antagonist, E28362 has demonstrated in vivo efficacy in preclinical models. It effectively reduces plasma lipid, liver cholesterol, and triglyceride content, positioning it as a therapeutic candidate for hyperlipidemia and atherosclerosis. These effects are mediated through its oral activity and ability to disrupt the PCSK9-LDLR interaction, leading to improved cholesterol management in living organisms.
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| Enzyme Assay |
The primary PCSK9 binding assay for E28362 involves surface plasmon resonance (SPR) or ELISA-based methods. Purified recombinant PCSK9 protein is immobilized on a sensor chip or plate, and increasing concentrations of E28362 are flowed over it to determine the binding affinity and kinetics. A complementary PCSK9-LDLR interaction ELISA is performed to assess the compound‘s ability to block the association of PCSK9 with the LDLR. These assays provide quantitative data on the compound's antagonistic activity.
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| Cell Assay |
HepG2 cells (human liver hepatocellular carcinoma) are seeded in 96-well plates and treated with varying concentrations of E28362 for 24-48 hours. Cell lysates are then analyzed by Western blotting using antibodies against LDLR and PCSK9 to determine protein levels. Additionally, the functional uptake of fluorescently-labeled LDL (DiI-LDL) is measured via flow cytometry or fluorescence microscopy to assess the enhancement of LDLR activity following E28362 treatment, confirming its efficacy in restoring cholesterol uptake.
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| Animal Protocol |
For in vivo efficacy evaluation, male C57BL/6 mice or golden Syrian hamsters are fed a high-cholesterol diet to induce hyperlipidemia. The animals are then orally administered E28362 daily for 2-4 weeks. Blood samples are collected at regular intervals to measure total cholesterol, LDL-cholesterol, and triglyceride levels. At the study endpoint, livers are harvested for analysis of LDLR protein levels via Western blot and for quantification of hepatic lipid content using biochemical assays.
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| ADME/Pharmacokinetics |
Tepotinib hydrochloride (brand name Tepmetko®) is a clinically approved, highly selective oral MET inhibitor developed by Merck KGaA/E MD Serono. It was first approved in Japan in March 2020 for the treatment of unresectable, advanced, or recurrent NSCLC with METex14 skipping mutations, followed by approvals in the US (February 2021) and EU (February 2022). The compound is also under investigation for other MET‑driven cancers and for combination therapies.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies in animals are not readily available for E28362; however, general safety data has been derived from in vitro assays. The compound has been observed to have no significant cytotoxicity in cultured liver cells, indicating a low potential for acute toxicity. As a research-grade PCSK9 inhibitor, it is not intended for human use, and standard safety precautions (gloves, lab coat, goggles) should be followed during handling to avoid exposure.
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| References | |
| Additional Infomation |
E28362 is an orally active small molecule PCSK9 antagonist that blocks the PCSK9-LDLR interaction. It is a promising lead compound for hyperlipidemia and atherosclerosis research. The compound is available for research use only and has not been approved for human therapeutic applications. It is distinct from biological PCSK9 inhibitors (monoclonal antibodies) and has the advantage of potential oral administration. Several suppliers offer E28362 with high purity (≥98%) for laboratory use.
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| Molecular Formula |
C16H19N3O3
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|---|---|
| Molecular Weight |
301.34
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| Exact Mass |
301.142
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| CAS # |
930017-01-9
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| PubChem CID |
16300305
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
-0.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
22
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| Complexity |
509
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(=O)NC(C2=CC=C(C)C=C2)C2C(=O)N(CC(O)C)CC=2N1
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| InChi Key |
FXSFMYTXKXGGCT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H19N3O3/c1-9-3-5-11(6-4-9)14-13-12(17-16(22)18-14)8-19(15(13)21)7-10(2)20/h3-6,10,14,20H,7-8H2,1-2H3,(H2,17,18,22)
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| Chemical Name |
6-(2-hydroxypropyl)-4-(4-methylphenyl)-1,3,4,7-tetrahydropyrrolo[3,4-d]pyrimidine-2,5-dione
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 3.3185 mL | 16.5926 mL | 33.1851 mL | |
| 5 mM | 0.6637 mL | 3.3185 mL | 6.6370 mL | |
| 10 mM | 0.3319 mL | 1.6593 mL | 3.3185 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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