PF-4136309

Catalog No.S8361 Batch:S836101

Technical Data

Formula	C₂₉H₃₁F₃N₆O₃
Molecular Weight	568.59	CAS No.	857679-55-1
Solubility (25°C)*	In vitro	DMSO	100 mg/mL (175.87 mM)
		Ethanol	100 mg/mL (175.87 mM)
		Water	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.)

Preparing Stock Solutions

Biological Activity

Description

PF-4136309 (INCB8761, PF-04136309) is a potent, selective, and orally bioavailable CCR2 antagonist with an IC50 of 5.2 nM for human CCR2.

Targets

CCR2 ^[1]

5.2 nM

In vitro

PF-4136309 is potent in inhibiting CCR2 mediated signaling events such as intracellular calcium mobilization and ERK (extracellular signal-regulated kinase) phosphorylation. <sup><a class="sref" href="#s_ref">[1]</a></sup>

In vivo

PF-4136309 exhibits >100-fold selectivity over other homologous chemokine receptors, a free fraction of 24% in human serum and 15% in mouse serum, and an oral bioavailability of 47% in mice, suitable as a tool compound for target validation in rodent models.<sup><a class="sref" href="#s_ref">[2]</a></sup>

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines Human PBMCs Concentrations 0.001 μM –10 μM Incubation Time 30 min Method 500,000 HPBMCs in serum free DMEM media are incubated with or without PF-4136309 and warmed to 37 °C. 400 μL of warmed 10 nM MCP-1 is added to the bottom chamber in all wells except the negative control. An 8 micron membrane filter is placed on top and the chamber lid is closed. Cells are then added to the holes in the chamber lid which are associated with the chamber wells below the filter membrane. The whole chamber is incubated at 37 °C, 5% CO2 for 30 min. The cells are then aspirated off, the chamber lid opened, and the filter gently removed. The filter is air dried and stained with Wright Geimsa stain. Filters are counted by microscopy. Antagonist potency is determined by comparing the number of cells that migrate to the bottom chamber in wells which contained antagonist, to the number of cells which migrate to the bottom chamber in MCP-1 control wells.
Animal Study:^{^[2]}	Animal Models Rats, Dogs Dosages 2 mg/kg Administration I.v.

Cell Assay:^{^[1]}

Cell lines
Human PBMCs
Concentrations
0.001 μM –10 μM
Incubation Time
30 min
Method
500,000 HPBMCs in serum free DMEM media are incubated with or without PF-4136309 and warmed to 37 °C. 400 μL of warmed 10 nM MCP-1 is added to the bottom chamber in all wells except the negative control. An 8 micron membrane filter is placed on top and the chamber lid is closed. Cells are then added to the holes in the chamber lid which are associated with the chamber wells below the filter membrane. The whole chamber is incubated at 37 °C, 5% CO2 for 30 min. The cells are then aspirated off, the chamber lid opened, and the filter gently removed. The filter is air dried and stained with Wright Geimsa stain. Filters are counted by microscopy. Antagonist potency is determined by comparing the number of cells that migrate to the bottom chamber in wells which contained antagonist, to the number of cells which migrate to the bottom chamber in MCP-1 control wells.

Animal Study:^{^[2]}

Animal Models
Rats, Dogs
Dosages
2 mg/kg
Administration
I.v.

References

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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.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.