PF-8380

Catalog No.S8218 Batch:S821803

Technical Data

Formula	C₂₂H₂₁Cl₂N₃O₅
Molecular Weight	478.33	CAS No.	1144035-53-9
Solubility (25°C)*	In vitro	DMSO	95 mg/mL (198.6 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

PF-8380 is a potent autotaxin (ATX) inhibitor with IC50 of 2.8 nM in an in vitro enzyme assay.

Targets

Autotaxin ^[1]
(Cell-free assay)

2.8 nM

In vitro

PF-8380 inhibits rat autotaxin with an IC50 of 1.16 nM with FS-3 substrate. In human whole blood incubated with compound for 2 h autotaxin was inhibited with an IC50 of 101 nM^[1].Inhibition of autotaxin by PF-8380 leads to decreased invasion, migtation and enhanced radiosensitization of GBM cells. Radiation-induced activation of Akt is abrogated by inhibition of ATX. Furthermore, inhibition of ATX leads to diminished tumor vascularity and delayed tumor growth^[2].

In vivo

Pre-treatment with PF-8380 prior to irradiation inhibited radiation-induced angiogenesis of tumor vascular endothelial cells and delayed progression of glioma tumor growth in vivo^[2]. Oral administration of 30 mg/kg PF8380 reduces inflammatory hyperalgesia in a rat air pouch model, exhibiting >95% reduction of LPA levels in both plasma and inflammatory site tissue within 3 hours^[1].

Protocol (from reference)

Cell Assay:^{^[2]}	Cell lines Mouse GL261 and Human U87-MG cells Concentrations 1 μM Incubation Time 45 min Method GL261 or U87-MG cells are plated in triplicate onto 6 cm plates and allowed to grow to 70% confluence. The semi-confluent cell layer is scratched with a sterile 200 μL pipette tip to create a scratch devoid of cells and plates are washed once with PBS to remove non-adherent cells and debris. For radiosensitization drug studies, cells are treated with 1 μM PF-8380 or DMSO for 45 min prior to irradiation with 4 Gy, and then incubated at 37°C in 5% CO2. Control plates are monitored for cell migration (20–24 h). Cells are fixed with 70% ethanol and stained with 1% methylene blue. To quantify migration, cells in three randomly selected high power fields (HPFs) in the scratched area are counted and normalized for surrounding cell density.
Animal Study:^{^[1]}	Animal Models Male Lewis rats Dosages 1, 3, 10, 30, and 100 mg/kg Administration by oral gavage

Cell Assay:^{^[2]}

Cell lines
Mouse GL261 and Human U87-MG cells
Concentrations
1 μM
Incubation Time
45 min
Method
GL261 or U87-MG cells are plated in triplicate onto 6 cm plates and allowed to grow to 70% confluence. The semi-confluent cell layer is scratched with a sterile 200 μL pipette tip to create a scratch devoid of cells and plates are washed once with PBS to remove non-adherent cells and debris. For radiosensitization drug studies, cells are treated with 1 μM PF-8380 or DMSO for 45 min prior to irradiation with 4 Gy, and then incubated at 37°C in 5% CO2. Control plates are monitored for cell migration (20–24 h). Cells are fixed with 70% ethanol and stained with 1% methylene blue. To quantify migration, cells in three randomly selected high power fields (HPFs) in the scratched area are counted and normalized for surrounding cell density.

Animal Study:^{^[1]}

Animal Models
Male Lewis rats
Dosages
1, 3, 10, 30, and 100 mg/kg
Administration
by oral gavage

References

Selleck's PF-8380 has been cited by 4 publications

Autotaxin suppresses cytotoxic T cells via LPAR5 to promote anti-PD-1 resistance in non-small cell lung cancer [ J Clin Invest, 2023, 133(17)e163128]	PubMed: 37655662
Autotaxin suppresses cytotoxic T cells via LPAR5 to promote anti-PD-1 resistance in non-small cell lung cancer [ J Clin Invest, 2023, 133(17)e163128]	PubMed: 37655662
EMT activates exocytotic Rabs to coordinate invasion and immunosuppression in lung cancer [ Proc Natl Acad Sci U S A, 2023, 120(28):e2220276120]	PubMed: 37406091
Aberrant ENPP2 expression promotes tumor progression in multiple myeloma [ Leuk Lymphoma, 2021, 1-12]	PubMed: 34847837

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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