PF-06446846
Based on 7 publication(s) in Google Scholar
PF-06446846 is an orally active proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. PF-06446846 directly and selectively inhibits translation of PCSK9 by stalling the 80S ribosome in the proximity of codon region.
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- Pureté: 98.35%
- CAS No.: 1632250-49-7
- Formule: C22H20ClN7O
- Masse moléculaire:433.89
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Pureté et documentation
- Références
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Help & FAQs
Publications Citing Use of MedChemExpress (MCE) PF-06446846
More- Cancer Commun (Lond). 2025 Aug;45(8):1010-1037. [Abstract]
- Protein Cell. 2021 Apr;12(4):240-260. [Abstract]
- Int J Biol Sci. 2024 Jul 15;20(10):3942-3955. [Abstract]
- BMC Cancer. 2024 Apr 10;24(1):445. [Abstract]
- IUBMB Life. 2026 Jun;78(6):e70119. [Abstract]
- Arch Oral Biol. 2025 Aug:176:106302. [Abstract]
- SSRN. 2025 Jun 18.
Customer Validation & Images
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Cell Proliferation/Viability Assay
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Apoptosis Analysis
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Cell Migration/Invasion Assay
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In Vivo Efficacy Study
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IHC
Activité biologique
Description
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| Bone marrow cell | IC50 |
1.15 μM
Compound: 1; PF-06446846
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Cytotoxicity against rat Bone marrow cell assessed as inhibition of cell growth with puromycin as high potent effect standard by celltiter-glo assay
Cytotoxicity against rat Bone marrow cell assessed as inhibition of cell growth with puromycin as high potent effect standard by celltiter-glo assay
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[PMID: 37379958] |
| Bone marrow cell | IC50 |
1.2 μM
Compound: 7f; PF-06446846
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Cytotoxicity against rat bone marrow cells assessed as reduction in cell viability after 72 hrs by CellTiter-Glo assay
Cytotoxicity against rat bone marrow cells assessed as reduction in cell viability after 72 hrs by CellTiter-Glo assay
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[PMID: 29878763] |
| Bone marrow cell | IC50 |
3.23 μM
Compound: 1; PF-06446846
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Cytotoxicity against rat Bone marrow cell assessed as inhibition of cell growth with (R)-4-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-N-(3-chloropyridin-2-yl)-N-(piperidin-3-yl) benzamide as high potent effect standard by celltiter-glo assay
Cytotoxicity against rat Bone marrow cell assessed as inhibition of cell growth with (R)-4-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-N-(3-chloropyridin-2-yl)-N-(piperidin-3-yl) benzamide as high potent effect standard by celltiter-glo assay
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[PMID: 37379958] |
| HeLa | IC50 |
0.5 μM
Compound: 14; PF-06446846
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Inhibition of PCSK9 expression in human HeLa cells after overnight incubation by ELISA
Inhibition of PCSK9 expression in human HeLa cells after overnight incubation by ELISA
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[PMID: 29519739] |
| Huh-7 | IC50 |
0.3 μM
Compound: 3; PF-06446846
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Binding affinity to 80S ribosome in human HuH7 cells expressing human C-terminal V5/6-His-tagged PCSK9 assessed as inhibition of PCSK9 secretion after 16 to 24 hrs by AlphaLISA method
Binding affinity to 80S ribosome in human HuH7 cells expressing human C-terminal V5/6-His-tagged PCSK9 assessed as inhibition of PCSK9 secretion after 16 to 24 hrs by AlphaLISA method
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[PMID: 30448414] |
| Huh-7 | IC50 |
0.38 μM
Compound: 7f; PF-06446846
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Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay
Binding affinity to 80S ribosome in human HuH7 cells harboring pCMV-truncated human PCSK9 (1 to 152 residues)-proLuc assessed as inhibition of PCSK9 mRNA translation after overnight incubation by luciferase reporter gene assay
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[PMID: 29878763] |
| Huh-7 | IC50 |
0.82 μM
Compound: 7f; PF-06446846
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Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA
Binding affinity to 80S ribosome in human HuH7 cells assessed as inhibition of PCSK9 mRNA translation after overnight incubation by ELISA
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[PMID: 29878763] |
| IEC-6 | IC50 |
>20 μM
Compound: 7f; PF-06446846
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Cytotoxicity against rat IEC-6 cells assessed as reduction in cell viability after 3 days by CellTiter-Glo assay
Cytotoxicity against rat IEC-6 cells assessed as reduction in cell viability after 3 days by CellTiter-Glo assay
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[PMID: 29878763] |
In Vitro
PF-06446846 inhibits the secretion of PCSK9 by Huh7 cells with an IC50 of 0.3 μM[1]. PF-06446846 inhibits PCSK9(1–35)-luciferase expression with an IC50 of 2 μM[1]. PF-06446846 (Compound 7f) shows rat bone marrow and human CD34+ toxicity[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:Rat bone marrow lineage (−) cell and CD34+ cell
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Concentration:0-20 µM
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Incubation Time:72 h
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Result:Showed cytotoxicity with IC50 values of 2.9 µM and 2.7 µM against rat Lin(−) and human CD34+, respectively.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male Sprague-Dawley (Crl:CD [SD] rats, five per group; 6–8 wk old at initiation of dosing)[1]
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Dosage:5, 15, and 50 mg/kg
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Administration:Oral administration, daily, 14 days
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Result:Reduced plasma PCSK9, total plasma cholesterol, and LDL-C (low-density lipoprotein cholesterol) in a dose-dependent manner without obvious toxicity.
Chemical Information
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CAS No. 1632250-49-7
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Appearance Solid
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Masse moléculaire 433.89
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Formule C22H20ClN7O
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Color Off-white to light yellow
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SMILES
O=C(C1=CC=C(C=C1)N2N=NC3=CC=CN=C32)N([C@H]4CNCCC4)C5=NC=CC=C5Cl
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Publications (7)
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Journal Impact Factor
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Most Recent
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Cancer Commun (Lond)
Lipid metabolism reprograming by SREBP1-PCSK9 targeting sensitizes pancreatic cancer to immunochemotherapy. [Abstract]2025 Aug;45(8):1010-1037. PMID: 40439109 -
Protein Cell
Potentiating CD8+ T cell antitumor activity by inhibiting PCSK9 to promote LDLR-mediated TCR recycling and signaling. [Abstract]2021 Apr;12(4):240-260. PMID: 33606190 -
Int J Biol Sci
Inhibition of PCSK9 enhances the anti-hepatocellular carcinoma effects of TCR-T cells and anti-PD-1 immunotherapy. [Abstract]2024 Jul 15;20(10):3942-3955. PMID: 39113701
PF-06446846 purchased from MedChemExpress. Usage Cited in: Int J Biol Sci. 2024 Jul 15;20(10):3942-3955. [Abstract]
PF-06446846 hydrochloride (PF; 5, 10 μM;12 h; then co-cultured with TCR-T cells (E: T = 1:1) for 24 h) enhanced killing activity of TCR-T cells in a concentration-dependent manner in HLA-A2+/AFP+HepG2 cells.
PF-06446846 purchased from MedChemExpress. Usage Cited in: Int J Biol Sci. 2024 Jul 15;20(10):3942-3955. [Abstract]
PF-06446846 hydrochloride (PF; 5, 10 μM;12 h; then co-cultured with TCR-T cells (E: T = 1:1) for 24 h) did not affect the apoptosis of TCR-T or HLA-A2+/AFP+HepG2 cells.
PF-06446846 purchased from MedChemExpress. Usage Cited in: Int J Biol Sci. 2024 Jul 15;20(10):3942-3955. [Abstract]
PF-06446846 hydrochloride (PF; 10 μM; 24+24 h) promoted a significant increase in chemotactic behavior of TCR-T cells and enhanced the TCR-T-mediated killing of HepG2 cells in the lower chamber.
PF-06446846 purchased from MedChemExpress. Usage Cited in: Int J Biol Sci. 2024 Jul 15;20(10):3942-3955. [Abstract]
PF-06446846 hydrochloride (PF; 5 mg/kg; every two days, i.p.) significantly inhibited HCC tumor growth and tumor weight in male C57BL/6J mice.
PF-06446846 purchased from MedChemExpress. Usage Cited in: Int J Biol Sci. 2024 Jul 15;20(10):3942-3955. [Abstract]
PF-06446846 hydrochloride (PF; 5 mg/kg; every two days, i.p.) demonstrated an augmented expression of CD3+ and CD8+ T cells in male C57BL/6J mice.
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BMC Cancer
Targeting PCSK9 to upregulate MHC-II on the surface of tumor cells in tumor immunotherapy. [Abstract]2024 Apr 10;24(1):445. PMID: 38600469 -
IUBMB Life
Mechanism of PCSK9-Mediated Macrophage Activation via the CAP1/NF-κB Pathway in CAWS-Induced Kawasaki Disease Vasculitis. [Abstract]2026 Jun;78(6):e70119. PMID: 42276750 -
Arch Oral Biol
2025 Aug:176:106302. PMID: 40435597 -
Solvant et solubilité
In Vitro:
DMSO : 100 mg/mL (230.47 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.76 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.76 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureté et documentation
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Fiche technique (282 KB)
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SDS (394 KB)
- English - EN (394 KB)
- Français - FR (394 KB)
- Deutsch - DE (394 KB)
- Norwegian - NO (394 KB)
- Español - ES (394 KB)
- Swedish - SV (394 KB)
- Italian - IT (394 KB)
- Korean - KR (394 KB)
- Portuguese - PT (394 KB)
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Instruction de manipulation (2659 KB)
Références
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.3047 mL | 11.5237 mL | 23.0473 mL | 57.6183 mL |
| 5 mM | 0.4609 mL | 2.3047 mL | 4.6095 mL | 11.5237 mL | |
| 10 mM | 0.2305 mL | 1.1524 mL | 2.3047 mL | 5.7618 mL | |
| 15 mM | 0.1536 mL | 0.7682 mL | 1.5365 mL | 3.8412 mL | |
| 20 mM | 0.1152 mL | 0.5762 mL | 1.1524 mL | 2.8809 mL | |
| 25 mM | 0.0922 mL | 0.4609 mL | 0.9219 mL | 2.3047 mL | |
| 30 mM | 0.0768 mL | 0.3841 mL | 0.7682 mL | 1.9206 mL | |
| 40 mM | 0.0576 mL | 0.2881 mL | 0.5762 mL | 1.4405 mL | |
| 50 mM | 0.0461 mL | 0.2305 mL | 0.4609 mL | 1.1524 mL | |
| 60 mM | 0.0384 mL | 0.1921 mL | 0.3841 mL | 0.9603 mL | |
| 80 mM | 0.0288 mL | 0.1440 mL | 0.2881 mL | 0.7202 mL | |
| 100 mM | 0.0230 mL | 0.1152 mL | 0.2305 mL | 0.5762 mL |
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