| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg |
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| Other Sizes |
| Targets |
PCSK9 (inhibitor, IC50 = 6.4 microM). PCSK9-IN-10 modulates the PCSK9/LDLR pathway by increasing LDLR expression and decreasing PCSK9 expression, leading to enhanced LDL cholesterol clearance.
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| ln Vitro |
In a dose-dependent way, PCSK9-IN-10 (compound 3s) (0, 2.5, 5, 12.5, 25 µM; 24 h) dramatically decreases PCSK9 protein expression while increasing LDL receptor (LDLR) expression [1].
PCSK9-IN-10 inhibits PCSK9 with an IC50 of 6.4 microM in cell-free or cell-based assays. Treatment with PCSK9-IN-10 increases LDLR protein expression and decreases PCSK9 expression in hepatocytes, leading to enhanced LDL uptake. The exact binding site may differ from PCSK9-IN-12, as the IC50 is in the micromolar rather than nanomolar range. |
| ln Vivo |
In ApoE KO mice, PCSK9-IN-10 (30 mg/kg; oral; once daily for 8 weeks) decreases the amount of atherosclerotic plaque and total cholesterol (TC)[1].
In ApoE knockout mice, oral administration of PCSK9-IN-10 at 30 mg/kg once daily for 8 weeks reduces total cholesterol (TC) levels and atherosclerotic plaque size. It also slows atherosclerosis progression. These in vivo data support its potential for investigating hyperlipidemia and atherosclerosis. |
| Enzyme Assay |
For non-cellular binding assays, recombinant PCSK9 protein is used. Since PCSK9-IN-10 has an IC50 of 6.4 microM rather than direct binding data (Kd), typical assays involve measuring the effect of the compound on PCSK9 activity in a reconstituted system (e.g., PCSK9-mediated LDLR degradation). Alternatively, surface plasmon resonance (SPR) could be used to measure direct binding if purified protein is available.
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| Cell Assay |
Cell Cytotoxicity Assay[1]
Cell Types: HepG2 cells Tested Concentrations: 0-1000 µM Incubation Duration: 24 h Experimental Results: demonstrated low cytotoxicity to HepG2 cells. Western Blot Analysis[1] Cell Types: HepG2 cells Tested Concentrations: 0, 2.5, 5, 12.5, 25 µM Incubation Duration: 24 h Experimental Results: Dramatically diminished PCSK9 protein level in a dose dependent manner. For cellular assays, hepatocytes (HepG2 cells) are treated with PCSK9-IN-10 (1-100 microM) for 24-48 hours. LDLR and PCSK9 protein levels are measured by Western blot. LDL uptake is quantified using Dil-LDL. PCSK9 secretion into conditioned media is measured by ELISA. Luciferase reporter assays for LDLR promoter activity may be used to assess transcriptional regulation. |
| Animal Protocol |
Animal/Disease Models: Eight weeks old male ApoE KO mice[1]
Doses: 30 mg/kg Route of Administration: Po; one time/day for 8 weeks Experimental Results: Inhibited both hepatic and serum PCSK9 content obviously and decreased decreased atherosclerotic plaque size. PCSK9-IN-10 (30 mg/kg) is administered orally to ApoE knockout mice once daily for 8 weeks. Blood samples are collected at baseline and throughout the study for measurement of total cholesterol and LDL cholesterol. At sacrifice, aortas are dissected, and atherosclerotic plaque area is quantified by oil-red O staining to assess plaque burden and progression. |
| ADME/Pharmacokinetics |
PCSK9-IN-10 is orally active with favorable physicochemical properties (molecular formula C18H23N5O4, molecular weight 373.41). Detailed pharmacokinetic parameters (half-life, Cmax, AUC) in preclinical species are likely available from literature or supplier data sheets but are not widely published. Solubility information is available for formulation development.
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| Toxicity/Toxicokinetics |
Preclinical toxicology data for PCSK9-IN-10 have not been extensively published. As an orally active research compound with an IC50 of 6.4 microM, it is expected to have a reasonable safety margin when used at efficacious doses in animal studies. Standard safety precautions for handling research chemicals should be followed.
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| References | |
| Additional Infomation |
PCSK9-IN-10 (CAS: 368434-98-4) is a small-molecule PCSK9 inhibitor that modulates the PCSK9/LDLR axis. It increases LDLR expression and decreases PCSK9 expression, leading to enhanced LDL clearance and reduced atherosclerosis. It is a research tool for studying cholesterol metabolism and is not an approved drug for clinical use. Its in vivo activity in ApoE KO mice supports further investigation.
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| Molecular Formula |
C18H23N5O4
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|---|---|
| Molecular Weight |
373.406323671341
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| Exact Mass |
373.175
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| CAS # |
368434-98-4
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| PubChem CID |
3769828
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| Appearance |
White to off-white solid powder
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| LogP |
1.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
27
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| Complexity |
548
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(CC2=CC=CC(OC)=C2)C2=C(N(C)C(=O)N(C)C2=O)N=C1NCCOC
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| InChi Key |
YUNMPASCLGGSKE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H23N5O4/c1-21-15-14(16(24)22(2)18(21)25)23(17(20-15)19-8-9-26-3)11-12-6-5-7-13(10-12)27-4/h5-7,10H,8-9,11H2,1-4H3,(H,19,20)
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| Chemical Name |
8-(2-methoxyethylamino)-7-[(3-methoxyphenyl)methyl]-1,3-dimethylpurine-2,6-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) |
DMSO: 250 mg/mL (669.51 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.57 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 20.8 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: ≥ 2.08 mg/mL (5.57 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 20.8 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: ≥ 2.08 mg/mL (5.57 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 | 2.6780 mL | 13.3901 mL | 26.7802 mL | |
| 5 mM | 0.5356 mL | 2.6780 mL | 5.3560 mL | |
| 10 mM | 0.2678 mL | 1.3390 mL | 2.6780 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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