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  3. INCB3344

INCB3344 

Cat. No.: HY-50674 Purity: 99.76%
Handling Instructions

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

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

INCB3344 Chemical Structure

INCB3344 Chemical Structure

CAS No. : 1262238-11-8

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10 mM * 1 mL in DMSO USD 241 In-stock
Estimated Time of Arrival: December 31
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10 mg USD 290 In-stock
Estimated Time of Arrival: December 31
50 mg USD 810 In-stock
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100 mg USD 1200 In-stock
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Customer Review

Based on 17 publication(s) in Google Scholar

Other Forms of INCB3344:

Top Publications Citing Use of Products

    INCB3344 purchased from MCE. Usage Cited in: Hypertension. 2012 Nov;60(5):1207-12.

    Effect of intervention with a CCR2 antagonist, INCB3344 (30 mg/kg per day), on deoxycorticosterone acetate (DOCA)/salt-induced increases in expression of CCR2 (A), CCL2 (B), CCL7 (C), CCL8 (D), and CCL12 (E) in aortas of mice.

    INCB3344 purchased from MCE. Usage Cited in: Hum Vaccin Immunother. 2017 Dec 2;13(12):2872-2882.

    Blockage of Ly6Chi monocytes abrogates HBV clearance by the 3 × GM-CSF+VACCINE. The AAV8–1.3HBV infected mice are treated with CCR2 antagonist (INCB 3344, 30 mg/kg) by intraperitoneal injection one hour before GM-CSF, repeated at day 2, 3, and 4. The CD11b+Ly6Chi monocytes are measured 12 hours after the fourth INCB 3344 administration.

    INCB3344 purchased from MCE. Usage Cited in: Oncotarget. 2018 Jul 13;9(76):34213-34228.

    The use of INCB 3344 leads to significant reduction of HBsAgs.

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    • Biological Activity

    • Protocol

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    • References

    • Customer Review

    Description

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

    IC50 & Target

    hCCR2

    5.1 nM (IC50)

    mCCR2

    9.5 nM (IC50)

    In Vitro

    INCB3344 is a potent antagonist towards rat and cynomolgus CCR2 as well, displaying IC50 values of 7.3 and 16 nM in binding antagonism and 2.7 and 6.2 nM in antagonism of chemotaxis activity, respectively. INCB3344 is a selective hCCR2 antagonist, exhibiting IC50 values of more than 1 μM against a panel of >50 ion channels, transporters, chemokine receptors and other selected GPCRs. It is also a selective mCCR2 antagonist, showing IC50 values of >1 μM and >3 μM against murine CCR1 and murine CCR5, respectively, the two most homologous chemokine receptors to mCCR2[1]. Characterization of the pharmacological activity of INCB3344 is first evaluated by testing its ability to inhibit CCL2 binding to CCR2 in a whole cell binding assay using a murine monocyte cell line, WEHI-274.1 and 125I-labeled mCCL2 as a tracer. The binding IC50 of INCB3344 in this assay is determined to be 10±5 nM, and inhibition of >90% binding is observed at a concentration of 90 nM[2].

    In Vivo

    When administered intravenously to CD-1 mice, INCB3344 exhibits a high clearance and a moderate volume of distribution, resulting in a short half life of 1 h. Despite its high clearance, however, good oral exposure is achieved, with an AUC at 2664 nM h at a dose of 10 mg/kg. The oral bioavailability is 47%. By comparison, slightly better oral exposure (AUC=3888 nM h) is obtained when administered orally to Balb/c mice at the same dose. This PK property, couple with its potent anti-mCCR2 activity and good selectivity, makes this compound suitable for model studies in rodents[1]. INCB3344 prevents deoxycorticosterone acetate (DOCA)/salt-induced changes in vascular expression of CCR2. In a separate series of experiments, CCR2 expression is elevated (≈1.5-fold higher) in aortas from mice that receive INCB3344 from days 7 to 21 of the DOCA/salt treatment period compare with sham animals; however, this level of CCR2 expression is significantly lower than that observed in the vehicle-treated group (P<0.05, n=6). Likewise, increased expression of its receptor ligand CCL2 in DOCA/salt-treated mice is blunted in mice receiving INCB3344 (P<0.05, n=6). By contrast, levels of CCL7, CCL8, and CCL12 are elevated to similar extents in DOCA/salt-treated mice receiving vehicle or INCB3344[3].

    Molecular Weight

    577.59

    Formula

    C₂₉H₃₄F₃N₃O₆

    CAS No.

    1262238-11-8

    SMILES

    CCO[[email protected]]1CN([[email protected]]2([H])CC[[email protected]@](CC2)(C3=CC4=C(OCO4)C=C3)O)C[[email protected]@H]1NC(CNC(C5=CC(C(F)(F)F)=CC=C5)=O)=O

    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : 240 mg/mL (415.52 mM; Need ultrasonic)

    H2O : < 0.1 mg/mL (insoluble)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 1.7313 mL 8.6567 mL 17.3133 mL
    5 mM 0.3463 mL 1.7313 mL 3.4627 mL
    10 mM 0.1731 mL 0.8657 mL 1.7313 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  5% DMSO    40% PEG300    5% Tween-80    50% saline

      Solubility: 6 mg/mL (10.39 mM); Clear solution; Need ultrasonic

    • 2.

      Add each solvent one by one:  5% DMSO    95% (20% SBE-β-CD in saline)

      Solubility: 6 mg/mL (10.39 mM); Clear solution; Need ultrasonic

    • 3.

      Add each solvent one by one:  5% DMSO    95% corn oil

      Solubility: 6 mg/mL (10.39 mM); Clear solution; Need ultrasonic

    *All of the co-solvents are provided by MCE.
    References
    Kinase Assay
    [2]

    WEHI 274.1 (murine monocytic cell line) cells are used in a whole cell binding assay. Cells (5×105) in RPMI 1640 (VWR), +0.1% BSA+20 mM HEPES (VWR), are added to various concentrations of INCB3344 in RPMI 1640 follow immediately by the addition of 150 pM 125I-labeled mCCL2 (mouse CCL2(JE)) and incubated for 30 min at room temperature (RT). For the nonspecific control, 0.3 μM mCCL2 is added in place of INCB3344. Cells are then harvested through 1.2-μm 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].

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

    Cell Assay
    [2]

    WEHI-274.1 cells (5×105) in RPMI 1640 (VWR) with or without various concentrations of INCB3344 in RPMI 1640 are loaded in the wells on top of an 8-μm polycarbonate filter in a 96-well-modified Boyden chamber. Beneath the filter, 30 nM mCCL2 with or without INCB3344 or media is placed in a corresponding 96-well plate. The sealed chambers are incubated for 45 min at 37°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-1α 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-1β as the ligand[2].

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

    Animal Administration
    [3][4]

    Mice[3]
    In a subset of experiments, DOCA/salt-treated mice are further randomly assigned to receive the CCR2 antagonist, INCB3344 (30 mg/kg per day; Haoyuan Chemexpress Co Ltd) or vehicle (10% DMSO/0.9% carboxymethylcellulose) via daily intraperitoneal injections commencing 10 days after induction of hypertension and continuing until the end of the 21-day treatment period. The normotensive control group for these experiments consist of sham-treated mice that receive vehicle from days 10 to 21.
    Rats[4]
    Adult male Sprague-Dawley rats (200-250 g) are used. After t=0 baseline measurement, rats are lightly anesthetized under an isoflurane/oxygen (5%; 2 L/min) flow and 25 μL of either saline (vehicle), 1 μg of CCL2 and/or 1 mM of INCB3344 is administered intrathecally between L5 and L6 vertebrae. Animals are tested once at 30, 60, 90, 120, and 240 min following drug administration. The percentage of maximal potential effect (MPE) is calculated for every time point.

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

    References

    Purity: 99.76%

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    KeyWords:

    INCB3344 | INCB 3344 | INCB-3344 | CCR | CC chemokine receptor | Inhibitor | inhibitor | inhibit

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