PF-8380 hydrochloride

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

Cat. No.: HY-13344A Purity: 98.59%: FAQs
Data Sheet SDS COA Handling Instructions

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PF-8380 hydrochloride 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 hydrochloride Chemical Structure

CAS No. : 2070015-01-7

Size	Price	Stock	Quantity
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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Based on 6 publication(s) in Google Scholar

Other Forms of PF-8380 hydrochloride:

PF-8380 In-stock

5 Publications Citing Use of MCE PF-8380 hydrochloride

: PF-8380 hydrochloride 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 hydrochloride 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)

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

514.79

Formula

C₂₂H₂₂Cl₃N₃O₅

CAS No.

2070015-01-7

Appearance

Solid

Color

White to off-white

SMILES

O=C(N1CCN(CC1)CCC(C2=CC(O3)=C(C=C2)NC3=O)=O)OCC4=CC(Cl)=CC(Cl)=C4.[H]Cl

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Solvent & Solubility

In Vitro:

DMSO : ≥ 5.2 mg/mL (10.10 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H₂O : < 0.1 mg/mL (insoluble)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	1.9425 mL	9.7127 mL	19.4254 mL
5 mM	0.3885 mL	1.9425 mL	3.8851 mL
10 mM	0.1943 mL	0.9713 mL	1.9425 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 (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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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

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In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

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μL

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

Calculation results:

Working solution concentration: mg/mL

Purity & Documentation

Purity: 98.59%

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Data Sheet (279 KB) SDS (251 KB)

COA (245 KB) HNMR (328 KB) LCMS (98 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]

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]

Complete Stock Solution Preparation Table

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

DMSO	1 mM	1.9425 mL	9.7127 mL	19.4254 mL	48.5635 mL
	5 mM	0.3885 mL	1.9425 mL	3.8851 mL	9.7127 mL
	10 mM	0.1943 mL	0.9713 mL	1.9425 mL	4.8563 mL