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5mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Purity: ≥98%
TAK-779 (TAK779) is a novel, potent and selective nonpeptide antagonist of CCR5 [C-C chemokine receptor type 5 (CCR5) receptor] and CXCR3 with potential anticancer, immunomodulatory and antiinflammatory activities. It efficiently and selectively inhibits R5 HIV-1 in MAGI-CCR5 cells, with EC50 and EC90 of 1.2 nM and 5.7 nM, respectively, and inhibits CCR5 with a Ki of 1.1 nM. It may be possible to treat HIV infection with TAK-779. The incidence and severity of experimental autoimmune encephalomyelitis were decreased by TAK-779 treatment. It significantly reduced the migration of leukocytes carrying CD4+, CD8+, and CD11b+ markers to the central nervous system (CNS). TAK-779 had no effect on T cell production of IFN-gamma, T cell expression of CXCR3, or the proliferation of anti-myelin oligodendrocyte glycoprotein T cells. TAK-779 also had no effect on antigen-presenting cells' IL-12 production, T cells' induction of CCR5, or the ability of myelin oligodendrocyte glycoprotein-specific T cells to spread experimental autoimmune encephalomyelitis.
Targets |
MIP-1α-CCR5 ( IC50 = 1 nM ); MIP-1β-CCR5 ( IC50 = 1 nM ); RANTES-CCR5 ( IC50 = 1.4 nM ); MCP-1-CCR2b ( IC50 = 27 nM ); R5 HIV-1 (Ba-L) ( EC50 = 1.2 nM ); R5 HIV-1 (Ba-L) ( EC90 = 5.7 nM ); R5 HIV-1 (Ba-L) ( EC50 = 3.7 nM ); R5 HIV-1 (Ba-L) ( EC90 = 12.8 nM ); R5 HIV-1 (KK) ( EC50 = 1.6 nM ); R5 HIV-1 (KK) ( EC90 = 20.8 nM ); R5 HIV-1 (HHA) ( EC50 = 3.2 nM ); R5 HIV-1 (HHA) ( EC90 = 7.5 nM ); R5 HIV-1 (CTV) ( EC50 = 3.5 nM ); R5 HIV-1 (CTV) ( EC90 = 27 nM ); mCXCR3( IC50 = 369 nM )
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ln Vitro |
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ln Vivo |
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Enzyme Assay |
The beta-chemokine receptor CCR5 is considered to be an attractive target for inhibition of macrophage-tropic (CCR5-using or R5) HIV-1 replication because individuals having a nonfunctional receptor (a homozygous 32-bp deletion in the CCR5 coding region) are apparently normal but resistant to infection with R5 HIV-1. In this study, we found that TAK-779, a nonpeptide compound with a small molecular weight (Mr 531.13), antagonized the binding of RANTES (regulated on activation, normal T cell expressed and secreted) to CCR5-expressing Chinese hamster ovary cells and blocked CCR5-mediated Ca2+ signaling at nanomolar concentrations. The inhibition of beta-chemokine receptors by TAK-779 appeared to be specific to CCR5 because the compound antagonized CCR2b to a lesser extent but did not affect CCR1, CCR3, or CCR4. Consequently, TAK-779 displayed highly potent and selective inhibition of R5 HIV-1 replication without showing any cytotoxicity to the host cells. The compound inhibited the replication of R5 HIV-1 clinical isolates as well as a laboratory strain at a concentration of 1.6-3.7 nM in peripheral blood mononuclear cells, though it was totally inactive against T-cell line-tropic (CXCR4-using or X4) HIV-1[1].
Binding Assays[1] CHO-K1 and CCR5-expressing CHO (CHO/CCR5) cells (5 × 104 cells per 100 μl) were cultured in a microtiter tray. After a 24-h incubation at 37°C, culture medium was replaced with the binding buffer [Ham’s F-12 medium containing 20 mM Hepes and 0.5% BSA (pH 7.2)]. Binding reactions were performed at room temperature for 40 min in the presence of [125I]-RANTES (specific activity: 2,000 Ci/mmol; Amersham Pharmacia) and various concentrations of the test compound. The binding reaction was terminated by washing out the free ligand with cold PBS, and the cell-associated radioactivity was counted by Top-count scintillation counter. Binding assays for other receptors, CCR1, CCR2b, CCR3, CCR4, and CXCR4, were carried out in a similar way. Ca2+ Mobilization Assays. [1] CHO/CCR5 cells (5 × 106 cells/ml) were suspended in the assay buffer (5 mM KCl/147 mM NaCl/0.22 mM KH2PO4/1.1 mM Na2HPO4/5.5 mM glucose/0.3 mM MgSO4/1 mM MgCl2/10 mM Hepes, pH 7.4). The cells were loaded with 5 μM Fura-PE3AM at 37°C for 30 min, were washed twice with the assay buffer containing 1 mM CaCl2, and were resuspended at 1 × 107 cells/ml in the same buffer. At 150 sec after exposure to TAK-779, 20 nM RANTES was added, and relative increase of cytoplasmic Ca2+ levels was monitored by F-2000 fluorescence spectrometer. Calibration was carried out with 50 μM ionomycin for total Ca2+ release and with 5 mM EGTA for Ca2+ chelating. |
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Cell Assay |
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Animal Protocol |
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References |
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Molecular Formula |
C33H39CLN2O2
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Molecular Weight |
531.127968072891
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Exact Mass |
530.27
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Elemental Analysis |
C, 74.63; H, 7.40; Cl, 6.67; N, 5.27; O, 6.02
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CAS # |
229005-80-5
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Related CAS # |
229005-80-5 (Cl); 263765-56-6 (cation)
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Appearance |
White to beige solid powder
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LogP |
8.17
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tPSA |
26.3
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SMILES |
CC1=CC=C(C=C1)C2=CC3=C(CCCC(=C3)C(=O)NC4=CC=C(C=C4)C[N+](C)(C)C5CCOCC5)C=C2.[Cl-]
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InChi Key |
VDALIBWXVQVFGZ-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C33H38N2O2.ClH/c1-24-7-11-27(12-8-24)28-14-13-26-5-4-6-29(22-30(26)21-28)33(36)34-31-15-9-25(10-16-31)23-35(2,3)32-17-19-37-20-18-32;/h7-16,21-22,32H,4-6,17-20,23H2,1-3H3;1H
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Chemical Name |
dimethyl-[[4-[[3-(4-methylphenyl)-8,9-dihydro-7H-benzo[7]annulene-6-carbonyl]amino]phenyl]methyl]-(oxan-4-yl)azanium;chloride
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Synonyms |
TAK-779 Chloride; TAK779; TAK 779
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
DMSO: ≥ 25 mg/mL (~47.1 mM)
H2O: ~16.7 mg/mL (~31.4 mM) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.58 mg/mL (4.86 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.58 mg/mL (4.86 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.58 mg/mL (4.86 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 50 mg/mL (94.14 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.8828 mL | 9.4139 mL | 18.8278 mL | |
5 mM | 0.3766 mL | 1.8828 mL | 3.7656 mL | |
10 mM | 0.1883 mL | 0.9414 mL | 1.8828 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Characterization of CHO/CCR5 cells and inhibitory effect of TAK-779 on [125I]-RANTES binding to the cells. Proc Natl Acad Sci U S A . 1999 May 11;96(10):5698-703. td> |
Inhibitory effects of TAK-779 on chemokine binding to CCR1-, CCR2b-, CCR3-, or CCR4-expressing CHO cells. Proc Natl Acad Sci U S A . 1999 May 11;96(10):5698-703 td> |
TAK-779 treatment did not affect myelin oligodendrocyte glycoprotein (MOG)-specific immune responses. Br J Pharmacol . 2009 Dec;158(8):2046-56. td> |
TAK-779 treatment inhibited cellular infiltration into the spinal cord of mice. Br J Pharmacol . 2009 Dec;158(8):2046-56. td> |
TAK-779 treatment decreased the infiltration of CXCR3 and CCR5 bearing leukocytes into the spinal cord. Br J Pharmacol . 2009 Dec;158(8):2046-56. td> |