| 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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| Other Sizes |
| Targets |
IC50: 5.7 μM (PCSK9)[1]
PCSK9‑IN‑11 targets PCSK9 by inhibiting its transcription. PCSK9 is a protein that binds to the LDL receptor (LDLR) and promotes its degradation, thereby reducing the clearance of LDL‑C from the bloodstream. By inhibiting PCSK9 transcription, the compound increases LDLR protein levels, enhancing LDL‑C clearance. |
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| ln Vitro |
In a dose-dependent manner, PCSK9-IN-11 (compound 5r) (0-25 μM, 24 h) dramatically lowers PCSK9 protein levels and boosts LDLR expression [1].
In vitro, PCSK9‑IN‑11 (0‑25 μM, 24 hours) significantly decreases PCSK9 protein level and increases LDLR expression in a dose‑dependent manner in HepG2 cells. It exhibits PCSK9 transcriptional inhibitory activity with an IC50 of 5.7 μM. These effects confirm its mechanism of action as a PCSK9 inhibitor. |
| ln Vivo |
The in vivo safety profile of PCSK9-IN-11 (compound 5r) (0-1000 mg/kg, gavage, once) is superior, as evidenced by its LD50 value surpassing 1000 mg/kg [1]. Significantly inhibiting liver PCSK9 expression and modestly lowering serum PCSK9 levels is PCSK9-IN-11 (30 mg/kg, gavage, once daily for 8 weeks) [1].
In vivo, PCSK9‑IN‑11 (30 mg/kg, oral gavage, once daily for 8 weeks) significantly suppresses hepatic PCSK9 expression and slightly reduces serum PCSK9 levels. The compound exhibits a good in vivo safety profile with a half‑lethal dose (LD50) value exceeding 1000 mg/kg. It does not affect body weight, behavioral characteristics, or survival in mice. |
| Enzyme Assay |
Non‑cellular assays for PCSK9‑IN‑11 are not typically performed as it functions as a transcriptional inhibitor. Its activity is assessed in cell‑based systems by measuring PCSK9 protein levels and LDLR expression. Target engagement can be assessed by measuring PCSK9 transcription using qRT‑PCR.
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| Cell Assay |
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. Markedly increased LDLR expression in a dose dependent manner.. Dramatically and dose-dependently increased DiI-LDL uptake by around 1.7 folds. In vitro cellular assays for PCSK9‑IN‑11 are performed using HepG2 cells. Cells are treated with the compound at concentrations of 0‑25 μM for 24 hours. PCSK9 protein levels are measured by Western blotting, and LDLR expression is assessed by Western blotting or qRT‑PCR. The IC50 for PCSK9 transcriptional inhibition is determined from dose‑response curves. |
| Animal Protocol |
Animal/Disease Models: C57BL/6J mice[1]
Doses: 0, 250, 500 or 1000 mg/kg Route of Administration: intragastrically (po) administered, single dose Experimental Results: demonstrated a good in vivo safety feature with the halflethal dose (LD50) value of over 1000 mg /kg. Did not affected the body weight, behavioral and survival characteristics of mice. Animal/Disease Models: ApoE KO mice (under high-fat diet (HFD))[1] Doses: 30 mg/kg Route of Administration: intragastric (po) administration, one time/day for 8 weeks Experimental Results: Dramatically suppressed hepatic PCSK9 expression and slightly decreased serum PCSK9 level. In vivo animal experiments for PCSK9‑IN‑11 are conducted in mouse models. The compound is administered via oral gavage at 30 mg/kg once daily for 8 weeks to assess its effects on hepatic PCSK9 expression and serum PCSK9 levels. Safety is evaluated at doses of 0‑1000 mg/kg to determine the LD50. Endpoints include PCSK9 expression, LDLR levels, and assessment of toxicity. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties for PCSK9‑IN‑11 indicate that it is orally active. The compound has a CAS number of 2882035‑56‑3. It exhibits a good in vivo safety profile with an LD50 exceeding 1000 mg/kg. The compound should be stored under appropriate conditions as per the manufacturer's instructions.
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| Toxicity/Toxicokinetics |
Toxicological data for PCSK9‑IN‑11 indicate a favorable safety profile. The half‑lethal dose (LD50) exceeds 1000 mg/kg in mice. At a dose of 30 mg/kg once daily for 8 weeks, the compound does not affect body weight, behavioral characteristics, or survival. These results suggest that PCSK9‑IN‑11 is well‑tolerated at therapeutic doses.
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| References | |
| Additional Infomation |
PCSK9‑IN‑11 (compound 5r) is a potent and orally active PCSK9 inhibitor with an IC50 of 5.7 μM for PCSK9 transcriptional inhibition in HepG2 cells. It increases LDL receptor protein levels and can be used for atherosclerosis research. The compound exhibits a good in vivo safety profile with an LD50 exceeding 1000 mg/kg. It is not approved for clinical use and is intended for research purposes only.
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| Molecular Formula |
C16H17CLFN5O3
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|---|---|
| Molecular Weight |
381.79
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| Appearance |
White to off-white solid powder
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 :~125 mg/mL (~327.41 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 | 2.6192 mL | 13.0962 mL | 26.1924 mL | |
| 5 mM | 0.5238 mL | 2.6192 mL | 5.2385 mL | |
| 10 mM | 0.2619 mL | 1.3096 mL | 2.6192 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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