Cat. No.: HY-120088

PF-06446846

7 Cited Publications

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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

Stockage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

PF-06446846 Chemical Structure

CAS No.: 1632250-49-7

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Activité biologique
- Description
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Publications (7)
Solvant et solubilité
- In Vitro
- In Vivo
Pureté et documentation
Références
Help & FAQs
Classifications
Bioz

Activité biologique

Description

Cellular Effect

Cell Line	Type	Value	Description	References
Bone marrow cell	IC₅₀	1.15 μM Compound: 1; PF-06446846	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	[PMID: 37379958]
Bone marrow cell	IC₅₀	1.2 μM Compound: 7f; PF-06446846	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	[PMID: 29878763]
Bone marrow cell	IC₅₀	3.23 μM Compound: 1; PF-06446846	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	[PMID: 37379958]
HeLa	IC₅₀	0.5 μM Compound: 14; PF-06446846	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	[PMID: 29519739]
Huh-7	IC₅₀	0.3 μM Compound: 3; PF-06446846	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	[PMID: 30448414]
Huh-7	IC₅₀	0.38 μM Compound: 7f; PF-06446846	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	[PMID: 29878763]
Huh-7	IC₅₀	0.82 μM Compound: 7f; PF-06446846	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	[PMID: 29878763]
IEC-6	IC₅₀	>20 μM Compound: 7f; PF-06446846	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	[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.

Cell Cytotoxicity Assay^[2]

Cell Line:

Rat bone marrow lineage (−) cell and CD34⁺ cell
Concentration:

0-20 µM
Incubation Time:

72 h
Result:

Showed cytotoxicity with IC₅₀ values of 2.9 µM and 2.7 µM against rat Lin(−) and human CD34⁺, respectively.

In Vivo

PF-06446846 reduces circulating PCSK9 and total plasma cholesterol levels in vivo without obvious toxicity^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Male Sprague-Dawley (Crl:CD [SD] rats, five per group; 6–8 wk old at initiation of dosing)^[1]
Dosage:

5, 15, and 50 mg/kg
Administration:

Oral administration, daily, 14 days
Result:

Reduced plasma PCSK9, total plasma cholesterol, and LDL-C (low-density lipoprotein cholesterol) in a dose-dependent manner without obvious toxicity.

Chemical Information

CAS No. 1632250-49-7
Appearance Solid
Masse moléculaire 433.89
Formule C₂₂H₂₀ClN₇O
Color Off-white to light yellow
SMILES

O=C(C1=CC=C(C=C1)N2N=NC3=CC=CN=C32)N([C@H]4CNCCC4)C5=NC=CC=C5Cl
Livraison

Room temperature in continental US; may vary elsewhere.

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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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
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

PCSK9 is a passenger gene in head and neck cancer with minimal pathological influence. [Abstract]

2025 May 21:176:106302. PMID: 40435597
SSRN

2025 Jun 18.

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

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

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.

Calculateur de molarité

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Calculateur de dilution

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

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.

Protocol 1

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.

Protocol 2

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.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (5.76 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
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

Pureté et documentation

Select Batch:

Pureté: 99.98%

Assay: 99.98%

ee.: 99.98%

Fiche technique (282 KB)
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)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Instruction de manipulation (2659 KB)

Références

[1]. Nathanael G Lintner, et al. Selective stalling of human translation through small-molecule engagement of the ribosome nascent chain. PLoS Biol. 2018 Apr 17;16(4):e1002628.

[2]. Allyn T. Londregan, et al. Small Molecule Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors: Hit to Lead Optimization of Systemic Agents. J Med Chem. 2018 Jul 12;61(13):5704-5718. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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

Keywords

PF-06446846

7 Cited Publications

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PF-06446846

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Publications Citing Use of MedChemExpress (MCE) PF-06446846

Activité biologique

Chemical Information

Publications (7)

Solvant et solubilité

Pureté et documentation

Références

Help & FAQs

Complete Stock Solution Preparation Table

PF-06446846

Metabolism/Protease Compound Library

Anti-Cardiovascular Disease Compound Library

Orally Active Compound Library

Heterocyclic Compound Library

Highly Selective Inhibitors Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

High-Throughput Bioactive Compound Library

Publications Citing Use of MedChemExpress (MCE) PF-06446846

Activité biologique

Chemical Information

Publications (7)

Solvant et solubilité

Pureté et documentation

Références

Help & FAQs

Complete Stock Solution Preparation Table

PF-06446846 Related Classifications

HY-120088 Related Classifications