PF-8380

Name: PF-8380
Brand: MedChemExpress
SKU: HY-13344
Rating: 5.0 (6 reviews)

Cat. No.: HY-13344 Purity: 99.04%: FAQs
Data Sheet SDS COA Handling Instructions

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PF-8380 is a potent autotaxin inhibitor with an IC₅₀ of 2.8 nM in isolated enzyme assay and 101 nM in human whole blood.

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

PF-8380 Chemical Structure

CAS No. : 1144035-53-9

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Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 55	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 55	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 50	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 80	In-stock	Estimated Time of Arrival: December 31
25 mg	USD 170	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 280	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 450	In-stock	Estimated Time of Arrival: December 31
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Customer Review

Based on 6 publication(s) in Google Scholar

Other Forms of PF-8380:

PF-8380 hydrochloride In-stock

5 Publications Citing Use of MCE PF-8380

: PF-8380 purchased from MedChemExpress. Usage Cited in: J Clin Invest. 2017 Apr 3;127(4):1517-1530. [Abstract]; Western blot analysis demonstrate decreased expression of dephosphorylated NFAT1 and total and active β-catenin proteins in allografts treated with PF-8380 (n = 4/group). All representative blots shown are from the same biological samples. Total and active β-catenin are blotted simultaneously on 2 parallel gels.

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PDE1 PDE2 PDE3 PDE4 PDE5 PDE6 PDE7 PDE9 PDE10 PDE11 PDE12 PDE8 Autotaxin

Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

PF-8380 is a potent autotaxin inhibitor with an IC₅₀ of 2.8 nM in isolated enzyme assay and 101 nM in human whole blood.

IC₅₀ & Target^[1]

Autotaxin

2.8 nM (IC₅₀, In isolated enzyme assay)

Cellular Effect

Cell Line	Type	Value	Description	References
A549	IC₅₀	> 20 μM Compound: PP-8380	Cytotoxicity against human A549 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay Cytotoxicity against human A549 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay	[PMID: 35436669]
A549	IC₅₀	8.21 μM Compound: PF-8380; 510k	Antiproliferative activity against human A549 cells measured after 72 hrs by MTT assay Antiproliferative activity against human A549 cells measured after 72 hrs by MTT assay	[PMID: 32535330]
HEK293	IC₅₀	1.7 nM Compound: PF-8380	Inhibition of recombinant human ATX beta expressed in HEK293 cells using LPC as substrate measured after 30 mins by LC-MS/MS analysis Inhibition of recombinant human ATX beta expressed in HEK293 cells using LPC as substrate measured after 30 mins by LC-MS/MS analysis	[PMID: 28743508]
HEK293	IC₅₀	2.8 nM Compound: PF-8380	Inhibition of recombinant ATX (unknown origin) expressed in HEK293 cells using FS-3 as substrate after 15 mins Inhibition of recombinant ATX (unknown origin) expressed in HEK293 cells using FS-3 as substrate after 15 mins	[PMID: 27544588]
HEK293	IC₅₀	2.8 nM Compound: PF-8380	Inhibition of recombinant human ATX beta expressed in HEK293 cells using FS-3 as substrate pretreated for 15 mins followed by substrate addition measured after 30 mins Inhibition of recombinant human ATX beta expressed in HEK293 cells using FS-3 as substrate pretreated for 15 mins followed by substrate addition measured after 30 mins	[PMID: 28743508]
HEK293	IC₅₀	2.8 nM Compound: 6; PF-8380	Inhibition of human ATX expressed in HEK293 cells using FS-3 as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins Inhibition of human ATX expressed in HEK293 cells using FS-3 as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins	[PMID: 27982588]
HEK293	IC₅₀	2.8 nM Compound: 21	Inhibition of recombinant human ATX expressed in HEK293 cells using FS3 as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins Inhibition of recombinant human ATX expressed in HEK293 cells using FS3 as substrate preincubated for 15 mins followed by substrate addition measured after 30 mins	[PMID: 26745766]
HEK293	IC₅₀	3 nM Compound: 2	Inhibition of human ATX expressed in HEK293 cells using FS-3 as substrate after 15 mins Inhibition of human ATX expressed in HEK293 cells using FS-3 as substrate after 15 mins	[PMID: 28165241]
Hep 3B2	IC₅₀	> 20 μM Compound: PP-8380	Cytotoxicity against human Hep3B cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay Cytotoxicity against human Hep3B cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay	[PMID: 35436669]
MCF7	IC₅₀	> 20 μM Compound: PP-8380	Cytotoxicity against human MCF-7 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay Cytotoxicity against human MCF-7 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay	[PMID: 35436669]
MCF7	IC₅₀	2.31 μM Compound: PF-8380; 510k	Antiproliferative activity against human MCF7 cells measured after 72 hrs by MTT assay Antiproliferative activity against human MCF7 cells measured after 72 hrs by MTT assay	[PMID: 32535330]
MDA-MB-231	IC₅₀	> 20 μM Compound: PP-8380	Cytotoxicity against human MDA-MB-231 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay Cytotoxicity against human MDA-MB-231 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay	[PMID: 35436669]
MDA-MB-231	IC₅₀	4.17 μM Compound: PF-8380; 510k	Antiproliferative activity against human MDA-MB-231 cells measured after 72 hrs by MTT assay Antiproliferative activity against human MDA-MB-231 cells measured after 72 hrs by MTT assay	[PMID: 32535330]
NCI-H1581	IC₅₀	> 20 μM Compound: PP-8380	Cytotoxicity against human NCI-H1581 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay Cytotoxicity against human NCI-H1581 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay	[PMID: 35436669]
NCI-H2228	IC₅₀	> 20 μM Compound: PP-8380	Cytotoxicity against human H2228 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay Cytotoxicity against human H2228 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay	[PMID: 35436669]
NCI-H2228	IC₅₀	11.27 μM Compound: PF-8380; 510k	Antiproliferative activity against human NCI-H2228 cells measured after 72 hrs by MTT assay Antiproliferative activity against human NCI-H2228 cells measured after 72 hrs by MTT assay	[PMID: 32535330]
RAW264.7	IC₅₀	9.58 μM Compound: PP-8380	Cytotoxicity against mouse RAW264.7 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay Cytotoxicity against mouse RAW264.7 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay	[PMID: 35436669]

In Vitro

PF-8380 also inhibits rat autotaxin with an IC₅₀ of 1.16 nM with FS-3 substrate. Potency of PF-8380 is maintained when using enzyme produced from fetal fibroblasts used in combination with lysophosphatidyl choline (LPC) as a substrate. In human whole blood incubated with PF-8380 for 2 h, autotaxin is inhibited with an IC₅₀ of 101 nM^[1]. Autotaxin (ATX), an enzyme with lysophospholipase D (lysoPLD) activity, catalyzes the production of lysophosphatidic acid (LPA) from lysophosphatidylcholine (LPC). Pre-treatment of GL261 and U87-MG cells with 1 μM PF-8380 followed by 4 Gy irradiation results in decreased clonogenic survival, decreases migration (33% in GL261; P=0.002 and 17.9% in U87-MG; P=0.012), decreases invasion (35.6% in GL261; P=0.0037 and 31.8% in U87-MG; P=0.002), and attenuates radiation-induced Akt phosphorylation^[2].

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

In Vivo

The pharmacokinetic profile of PF-8380 is evaluated at an intravenous dose of 1 mg/kg and oral doses of 1 to 100 mg/kg out to 24 h. PF-8380 has mean clearance of 31 mL/min/kg, volume of distribution at steady state of 3.2 L/kg, and effective t_1/2 of 1.2 h. Oral bioavailability is moderate, ranging from 43 to 83%. Plasma concentrations increased with single oral escalating doses, but C_max increased at a rate that is approximately proportional to dose from 1 to 10 mg/kg and less than proportional to dose from 10 to 100 mg/kg. PF-8380 exposures estimated by area under the curve are approximately proportional to dose and linear up to 100 mg/kg. Plasma C16:0, C18:0, and C20:0 LPA levels are measured immediately after collection. Maximal reduction of LPA levels is observed by the 3 mg/kg dose at 0.5 h with all LPA returning at or above baseline at 24 h^[1]. Treatment with 10 mg/kg PF-8380 increases tumor-associated vascularity modestly by 20% (P=0.497). When compared to control, treatment of PF-8380 45 min before 4 Gy irradiation decreases vascularity by nearly 48% when compared to control (P=0.031) and by 65% when compared to mice that received radiation alone (P=0.011)^[2].

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

Molecular Weight

478.33

Formula

C₂₂H₂₁Cl₂N₃O₅

CAS No.

1144035-53-9

Appearance

Solid

Color

White to light brown

SMILES

O=C(N1CCN(CC1)CCC(C2=CC(O3)=C(C=C2)NC3=O)=O)OCC4=CC(Cl)=CC(Cl)=C4

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (209.06 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	2.0906 mL	10.4530 mL	20.9061 mL
5 mM	0.4181 mL	2.0906 mL	4.1812 mL
10 mM	0.2091 mL	1.0453 mL	2.0906 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

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: ≥ 0.67 mg/mL (1.40 mM); Clear solution

This protocol yields a clear solution of ≥ 0.67 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (6.7 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: ≥ 0.67 mg/mL (1.40 mM); Clear solution

This protocol yields a clear solution of ≥ 0.67 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (6.7 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: ≥ 0.67 mg/mL (1.40 mM); Clear solution

This protocol yields a clear solution of ≥ 0.67 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 (6.7 mg/mL) to 900 μL Corn oil, and mix evenly.

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
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: 50% PEG300 50% Saline
Solubility: 10 mg/mL (20.91 mM); Suspended solution; Need ultrasonic

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: 99.04%

Select Batch:

Data Sheet (279 KB) SDS (252 KB)

COA (244 KB) LCMS (268 KB)

Handling Instructions (2659 KB)

References

[1]. Gierse J, et al. A novel autotaxin inhibitor reduces lysophosphatidic acid levels in plasma and the site of inflammation. J Pharmacol Exp Ther. 2010 Jul;334(1):310-7. [Content Brief]

[2]. Bhave SR, et al. Autotaxin Inhibition with PF-8380 Enhances the Radiosensitivity of Human and Murine Glioblastoma Cell Lines. Front Oncol. 2013 Sep 17;3:236. [Content Brief]

[3]. Cao P, et al. Autocrine lysophosphatidic acid signaling activates β-catenin and promotes lung allograft fibrosis. J Clin Invest. 2017 Apr 3;127(4):1517-1530. [Content Brief]

Kinase Assay ^[1]	FS-3 substrate is solubilized in assay buffer at 500 μM and frozen at -20°C in single-use aliquots for up to 4 weeks. Recombinant autotaxin is diluted in Tris-buffered saline (140 mM NaCl, 5 mM KCl, 1 mM CaCl₂, 1 mM MgCl₂, 50 mM Tris, pH 8.0) and incubated with compound in DMSO or DMSO alone (final 1% DMSO) for 15 min at 37°C, and the reaction is started with the addition of FS-3 at a final concentration of 1 μM. The reaction is allowed to proceed at 37°C for 30 min and monitored at 520 nm until the uninhibited control compared with a no-enzyme control gave a Z′≥0.5. IC₅₀s are determined in triplicate by using a four-parameter fit^[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay ^[2]	HUVEC (1×10⁶) and bEnd.3 cells (1×10⁶) are plated in 100 mm plates and after 24 h, U87-MG (2×10⁶) and GL261 (2×10⁶) cells are plated onto transwell inserts. After co-culture for 24 h, cells are treated with 1 μM of PF-8380 or vehicle control DMSO for 45 min prior to irradiation with 0, 2, 4, 6, or 8 Gy. After the treatments as co-culture with either PF-8380 or DMSO calculated numbers of U87-MG and GL261 cells are plated to enable normalization for plating efficiencies. After 7 to 10 day incubation plates are fixed with 70% EtOH and stained with 1% methylene blue. Colonies consisting of >50 cells are counted by viewing the plates under a microscope. The survival fractions are calculated as (number of colonies/number of cells plated)/(number of colonies for corresponding control/number of cells plated). Survival curves are analyzed by curve fitting to the alpha/beta model calculating D₀ and n^[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[1]^[2]	Rats^[1] Male Lewis rats weighing 275 to 300 g are used and acclimated to their surroundings for approximately 1 week with food and water provided ad libitum. A minimum of 1 day before study, animals are anesthetized with isoflurane (to effect) and implanted with Culex vascular catheters in the carotid artery. Animals are acclimated in Culex cages overnight before dosing. Patency of the carotid artery catheter is maintained by using the "tend" function of the Culex automated blood sampler. Animals are dosed with PF-8380 at 1, 3, 10, 30, and 100 mg/kg by oral gavage after an overnight fast. Blood collections are obtained from the carotid artery and performed by the Culex automated blood sampler at 0.25, 0.5, 1, 2, 4, 6, 8, and 24 h after administration. Blood is centrifuged, and plasma is collected for analysis of PF-8380 and LPA concentrations. Mice^[2] GL261 cells (1×10⁶) are injected into the right hind limb of nude mice. Once tumors are palpable the mice are serpentine sorted into groups of six to seven animals representing similar distributions of tumor sizes (range=240 mm³). Tumor bearing mice are injected intraperitoneally with vehicle (DMSO) or PF-8380 at 10 mg/kg body weight once daily for five consecutive days. Forty five minutes after drug injection, mice are anesthetized with isoflurane and positioned in the RS2000 irradiator. They are then irradiated with 2 Gy daily for five consecutive days for a total of 10 Gy. Lead blocks (10 mm thick) are used to shield the head, thorax, and abdomen. Tumor size is monitored longitudinally using an external traceable digital caliper. Mice are sacrificed by cervical dislocation once the tumors reached a volume of approximately 10 mm³ or when ulceration becomes apparent. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Gierse J, et al. A novel autotaxin inhibitor reduces lysophosphatidic acid levels in plasma and the site of inflammation. J Pharmacol Exp Ther. 2010 Jul;334(1):310-7. [Content Brief] [2]. Bhave SR, et al. Autotaxin Inhibition with PF-8380 Enhances the Radiosensitivity of Human and Murine Glioblastoma Cell Lines. Front Oncol. 2013 Sep 17;3:236. [Content Brief] [3]. Cao P, et al. Autocrine lysophosphatidic acid signaling activates β-catenin and promotes lung allograft fibrosis. J Clin Invest. 2017 Apr 3;127(4):1517-1530. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.0906 mL	10.4530 mL	20.9061 mL	52.2652 mL
	5 mM	0.4181 mL	2.0906 mL	4.1812 mL	10.4530 mL
	10 mM	0.2091 mL	1.0453 mL	2.0906 mL	5.2265 mL
	15 mM	0.1394 mL	0.6969 mL	1.3937 mL	3.4843 mL
	20 mM	0.1045 mL	0.5227 mL	1.0453 mL	2.6133 mL
	25 mM	0.0836 mL	0.4181 mL	0.8362 mL	2.0906 mL
	30 mM	0.0697 mL	0.3484 mL	0.6969 mL	1.7422 mL
	40 mM	0.0523 mL	0.2613 mL	0.5227 mL	1.3066 mL
	50 mM	0.0418 mL	0.2091 mL	0.4181 mL	1.0453 mL
	60 mM	0.0348 mL	0.1742 mL	0.3484 mL	0.8711 mL
	80 mM	0.0261 mL	0.1307 mL	0.2613 mL	0.6533 mL
	100 mM	0.0209 mL	0.1045 mL	0.2091 mL	0.5227 mL

PF-8380 Related Classifications

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-83801144035-53-9PF8380PF 8380Phosphodiesterase (PDE)Inhibitorinhibitorinhibit

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PF-8380

Customer Review

Other Forms of PF-8380:

PF-8380 Related Antibodies

5 Publications Citing Use of MCE PF-8380

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View All Phosphodiesterase (PDE) Isoform Specific Products:

Biological Activity

Protocol

Purity & Documentation

References

Customer Review

PF-8380 Related Antibodies

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Dilution Calculator

Complete Stock Solution Preparation Table

PF-8380 Related Classifications

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