INCB3344, inhibitor

INCB3344

Cat. Num. AAA5764359

• Purity: 98.00%
• Synonyms: INCB3344; inhibitor

• Purity/Purification: 98.00%
• Form/Format: Solid. Powder

• Solubility: DMSO: 236mg/mL (408.59mM) Need ultrasonic; Water: Insoluble; (<1mg/ml refers to the product slightly soluble or insoluble)
• Formula: C29H34F3N3O6
• SMILES: CCOC1CN(CC1NC(=O)CNC(=O)C2=CC(=CC=C2)C(F)(F)F)C3CCC(CC3)(C4=CC5=C(C=C4)OCO5)O
• CAS Number: 1262238-11-8
• Cell Research: WEHI-274.1 cells (5x10^5) in RPMI 1640 (VWR) with or without various concentrations of INCB3344 in RPMI 1640 are loaded in the wells on top of an 8-um polycarbonate filter in a 96-well-modified Boyden chamber. Beneath the filter, 30nM mCCL2 with or without INCB3344 or media is placed in a corresponding 96-well plate. The sealed chambers are incubated for 45 minutes at 37 degree C, 5% CO2. Filters are washed, stained with Wright-Giemsa, and the number of cells that migrate toward mCCL2 in the bottom chamber counted by microscopy. The ability of INCB3344 to antagonize CCR2-mediated chemotaxis is reported as the inhibitor concentration required for IC50 values of specific migration to mCCL2. Specific migration is defined as the total migration minus the background migration. A similar assay is used to determine the impact of INCB3344 on CCR1-mediated chemotaxis of WEHI-274.1 cells, by using mouse MIP-1alpha as a ligand. In addition C5a, FMLP and RANTES are similarly tested in the presence of INCB3344 for migration of WEHI-274.1 cells. For the studies on the impact of INCB3344 on CCR5-mediated chemotaxis, murine T cells are used as the cell system with mouse MIP-1beta as the ligand [2].
• Kinase Assay: Cells (5x10^5) in RPMI 1640 (VWR), +0.1% BSA+20mM HEPES (VWR), are added to various concentrations of INCB3344 in RPMI 1640 followed immediately by the addition of 150pM 125I-labeled mCCL2 (mouse CCL2(JE)) and incubated for 30 minutes at room temperature (RT). For the nonspecific control, 0.3uM mCCL2 is added in place of INCB3344. Cells are then harvested through 1.2-um polyvinylidene difluoride filters, the filters are air-dried, and binding is determined by counting in a gamma counter. Antagonist activity is reported as the inhibitor concentration required for IC50 of specific binding. Specific binding is defined as the total binding minus the nonspecific binding and typically represents 97% of the total binding [2].
• Preparation and Storage: Store at -20 degree C for 3 years powder; -80 degree C for 2 years in solvent

Related Product Information for INCB3344, inhibitor

INCB3344 is an effective, specific and orally bioavailable CCR2 antagonist with IC50 values of 9.5nM (mCCR2) and 5.1nM (hCCR2) in binding antagonism and 7.8nM (mCCR2) and in 3.8nM (hCCR2) antagonism of chemotaxis activity.

Product Categories/Family for INCB3344, inhibitor

Immunology/Inflammation; CCR

References

Xue CB, et al. Discovery of INCB3344, a potent, selective and orally bioavailable antagonist of human and murine CCR2. Bioorg Med Chem Lett. 2010 Dec 15;20(24):7473-8
Xue CB, et al. Discovery of INCB3344, a potent, selective and orally bioavailable antagonist of human and murine CCR2. Bioorg Med Chem Lett. 2010 Dec 15;20(24):7473-8
Brodmerkel CM, et al. Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344. J Immunol. 2005 Oct 15;175(8):5370-8.
Brodmerkel CM, et al. Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344. J Immunol. 2005 Oct 15;175(8):5370-8.
Chan CT, et al. Reversal of vascular macrophage accumulation and hypertension by a CCR2 antagonist in deoxycorticosterone/salt-treated mice. Hypertension. 2012 Nov;60(5):1207-12.
Chan CT, et al. Reversal of vascular macrophage accumulation and hypertension by a CCR2 antagonist in deoxycorticosterone/salt-treated mice. Hypertension. 2012 Nov;60(5):1207-12.
Dansereau MA, et al. Spinal CCL2 pronociceptive action is no longer effective in CCR2 receptor antagonist-treated rats. J Neurochem. 2008 Jul;106(2):757-69.
Dansereau MA, et al. Spinal CCL2 pronociceptive action is no longer effective in CCR2 receptor antagonist-treated rats. J Neurochem. 2008 Jul;106(2):757-69.