| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
PCSK9 (Proprotein convertase subtilisin/kexin type 9). PF-06446846 hydrochloride is an orally active and highly selective inhibitor of PCSK9 translation. It inhibits PCSK9 by inducing ribosome stalling.
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| ln Vitro |
PF-06446846 inhibits Huh7 cells from secreting PCSK9, with an IC50 of 0.3 μM[1].
PF-06446846 hydrochloride is a highly selective inhibitor of PCSK9 translation. It inhibits PCSK9 by inducing ribosome stalling. By inhibiting PCSK9 synthesis, it may reduce circulating PCSK9 levels and increase LDL receptor availability, leading to lower LDL cholesterol. |
| ln Vivo |
In a dose-dependent manner, PF-06446846 (oral gavage; 5–50 mg/kg/day for 14 days) decreases total cholesterol levels and plasma PCSK9 [1].
PF-06446846 hydrochloride is an orally active PCSK9 inhibitor. As a selective inhibitor of PCSK9 translation, it has potential applications in the study of cholesterol metabolism and dyslipidemia. Its oral activity makes it a valuable tool for in vivo studies of PCSK9 regulation. |
| Enzyme Assay |
PCSK9 translation inhibition assays are performed in cell lines expressing PCSK9 (e.g., HepG2 cells). Cells are cultured in appropriate media and treated with PF-06446846 hydrochloride at various concentrations. PCSK9 protein levels in cell lysates and culture supernatants are measured by ELISA or Western blotting. PCSK9 mRNA levels are measured by qRT-PCR to confirm translational (rather than transcriptional) inhibition. Ribosome stalling is assessed by ribosome profiling or polysome analysis. IC50 values for PCSK9 protein reduction are determined by non-linear regression.
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| Cell Assay |
Cellular PCSK9 inhibition is evaluated in hepatocyte cell lines (e.g., HepG2, Huh-7). Cells are cultured in appropriate media at 37°C with 5% CO2 and treated with PF-06446846 hydrochloride at various concentrations for 24-72 hours. PCSK9 protein levels in cell lysates and culture supernatants are measured by ELISA or Western blotting. LDL receptor levels are measured by Western blotting or flow cytometry. Cell viability is assessed using MTT or LDH assays. Each experiment includes vehicle controls and known PCSK9 inhibitors as positive controls.
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| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) (Crl:CD [SD] rat, 6-8 weeks old at time of dosing initiation) [1]
Doses: 5, 15, and 50 mg/kg Route of Administration: po (oral gavage); daily Once, for 14 days Experimental Results: Lowered plasma PCSK9 and lowered total cholesterol levels in a dose-dependent manner. In vivo efficacy is evaluated in animal models of hypercholesterolemia (e.g., high-fat diet-fed mice or rats). PF-06446846 hydrochloride is administered orally at doses determined by preclinical studies. Plasma PCSK9 levels are measured by ELISA. Plasma lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides) is measured. Liver tissue is collected for PCSK9 and LDL receptor protein analysis. Sample sizes typically range from 6-10 animals per group. |
| ADME/Pharmacokinetics |
Molecular Weight: 470.35. Formula: C22H21Cl2N7O. CAS No.: 1632250-50-0. Purity: ≥98%. Synonyms: PF-06446846, PF 06446846. For research use only.
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| Toxicity/Toxicokinetics |
No comprehensive toxicology data are publicly available. As a PCSK9 translation inhibitor, potential toxicities may include effects on cholesterol metabolism and liver function. Standard toxicity studies would include acute and subchronic toxicity in rodents, genotoxicity screening, and evaluation of effects on the liver and lipid metabolism. No clinical trials have been reported for this compound. The compound is intended for research use only.
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| References | |
| Additional Infomation |
PF-06446846 hydrochloride is also known as PF-06446846, PF 06446846. It is an orally active and highly selective inhibitor of PCSK9 translation. It inhibits PCSK9 by inducing ribosome stalling. No clinical trials or regulatory approvals have been reported. The compound is for research use only.
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| Molecular Formula |
C22H21CL2N7O
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|---|---|
| Molecular Weight |
433.8935
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| Exact Mass |
433.141
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| CAS # |
1632250-50-0
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| Related CAS # |
PF-06446846;1632250-49-7
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| PubChem CID |
145925649
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| Appearance |
Light yellow to khaki solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
655.5±65.0 °C at 760 mmHg
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| Flash Point |
350.2±34.3 °C
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| Vapour Pressure |
0.0±2.0 mmHg at 25°C
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| Index of Refraction |
1.745
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| LogP |
1.86
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
32
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| Complexity |
617
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1C[C@H](CNC1)N(C2=C(C=CC=N2)Cl)C(=O)C3=CC=C(C=C3)N4C5=C(C=CC=N5)N=N4.Cl
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| InChi Key |
AQSJYIVIWBIHOU-UNTBIKODSA-N
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| InChi Code |
InChI=1S/C22H20ClN7O.ClH/c23-18-5-2-12-25-20(18)29(17-4-1-11-24-14-17)22(31)15-7-9-16(10-8-15)30-21-19(27-28-30)6-3-13-26-21/h2-3,5-10,12-13,17,24H,1,4,11,14H21H/t17-/m1./s1
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| Chemical Name |
N-(3-Chloropyridin-2-yl)-N-((3R)-piperidin-3-yl)-4-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)benzamide hydrochloride
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| Synonyms |
PF‑06446846 PF 06446846 PF-06446846 hydrochloridePF6446846
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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: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 (~531.52 mM)
H2O : ~100 mg/mL (~212.61 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.42 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 (4.42 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 (4.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (212.61 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3047 mL | 11.5237 mL | 23.0473 mL | |
| 5 mM | 0.4609 mL | 2.3047 mL | 4.6095 mL | |
| 10 mM | 0.2305 mL | 1.1524 mL | 2.3047 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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