PF-06446846

Name: PF-06446846
Brand: MedChemExpress
SKU: HY-120088
Rating: 5.0 (6 reviews)

Cat. No.: HY-120088 Purity: 98.35%: Data Sheet
COA

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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.

For research use only. We do not sell to patients.

PF-06446846 Chemical Structure

CAS No. : 1632250-49-7

Size	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	In-stock	Estimated Time of Arrival: December 31
10 mg	In-stock	Estimated Time of Arrival: December 31
25 mg	In-stock	Estimated Time of Arrival: December 31
50 mg	In-stock	Estimated Time of Arrival: December 31
100 mg	In-stock	Estimated Time of Arrival: December 31
200 mg	Get quote
500 mg	Get quote

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Customer Review

Based on 6 publication(s) in Google Scholar

Other Forms of PF-06446846:

PF-06446846 hydrochloride In-stock

6 Publications Citing Use of MCE PF-06446846

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Biological Activity
Purity & Documentation
References
Customer Review

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.

Molecular Weight

433.89

Formula

C₂₂H₂₀ClN₇O

CAS No.

1632250-49-7

Appearance

Solid

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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

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

Solvent & Solubility

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)

Preparing
Stock Solutions

Concentration Solvent Mass	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

View the 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.

Molarity Calculator
Dilution Calculator

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

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

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

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.

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.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
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.
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.
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

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

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

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

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

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).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

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.

Purity & Documentation

Purity: 98.35%

Select Batch:

Data Sheet (282 KB) SDS (394 KB)

COA (259 KB) HNMR (145 KB) RP-HPLC (171 KB) LCMS (108 KB)

Handling Instructions (2659 KB)

References

[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]

Complete Stock Solution Preparation Table

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

PF-06446846 Related Classifications

Cardiovascular Disease

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

PF-064468461632250-49-7PF06446846PF 06446846PCSK9Proprotein convertase subtilisin/kexin type 9Selective80S ribosomeHuh7Rat bone marrowInhibitorinhibitorinhibit

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PF-06446846

Customer Review

Other Forms of PF-06446846:

PF-06446846 Related Antibodies

6 Publications Citing Use of MCE PF-06446846

Featured Recommendations

•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

Biological Activity

Purity & Documentation

References

Customer Review

PF-06446846 Related Antibodies

Molarity Calculator

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Complete Stock Solution Preparation Table

PF-06446846 Related Classifications

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