| 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 |
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PF‑06446846 HCL (PF-6446846; PF6446846) is a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor with anti-hyperlipidemic effects. It inhibits the translation of PCSK9 by inducing the ribosome to stall around codon, mediated by the sequence of the nascent chain within the exit tunnel. PF-06446846 reduces plasma PCSK9 and total cholesterol levels in rats following oral dosing. PF-06446846 is highly selective for the inhibition of PCSK9 translation. Inhibiting PCSK9 can potentiate CD8 + T cell antitumor activity by promoting LDLR-mediated TCR recycling and signaling. Thus PCSK9/LDLR may serve as a potential target for cancer immunotherapy as well.
| ln Vitro |
PF-06446846 inhibits Huh7 cells from secreting PCSK9, with an IC50 of 0.3 μM[1].
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| 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].
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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. |
| References |
[1]. Lintner NG, et al. Selective stalling of human translation through small-molecule engagement of the ribosome nascent chain. PLoS Biol. 2017 Mar 21;15(3):e2001882.
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| Molecular Formula |
C22H21CL2N7O
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|---|---|
| Molecular Weight |
433.8935
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| CAS # |
1632250-50-0
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| Related CAS # |
PF-06446846;1632250-49-7
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| SMILES |
O=C(N(C1=NC=CC=C1Cl)[C@H]2CNCCC2)C3=CC=C(N4N=NC5=CC=CN=C54)C=C3.[H]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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| 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 (~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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