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Purity: ≥98%
| Targets |
TAK-220 targets the C-C chemokine receptor type 5 (CCR5), a G protein-coupled receptor that serves as a co-receptor for HIV-1 entry into CD4+ T cells. CCR5 is also involved in the regulation of immune cell migration and inflammation through its interaction with chemokines such as RANTES (CCL5) and MIP-1α (CCL3). TAK-220 is a selective CCR5 antagonist that blocks the binding of these chemokines to the receptor. The compound inhibits MIP-1α binding with an IC50 of 1.4 nM and RANTES binding with an IC50 of 3.5 nM. TAK-220 shows no effect on binding to CCR1, CCR2b, CCR3, CCR4, or CCR7, demonstrating its selectivity for CCR5.
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| ln Vitro |
TAK-220 is a selective CCR5 antagonist that, in CHO cells, shows IC50s of 3.5 nM and 1.4 nM, respectively, inhibiting the binding of RANTES and MIP-1α to CCR5, but not the binding to CCR1, CCR2b, or CCR3. CCR7 or CCR4. TAK-220 (0-1000 nM) inhibits CCR5-mediated Casup>2+ signaling and binds with CCR5 but not RANTES. With an IC50 value of 0.42 nM, TAK-220 inhibits R5 HIV-1 (JR-FL) envelope-mediated membrane fusion, while it has no effect on X4 HIV-1 (HXB2) envelope-mediated membrane fusion. With EC50 values of 1.2 nM (HIV-1 KK), 0.72 nM (HIV-1 CTV), 1.7 nM (HIV-1 HKW), 1.7 nM (HIV-1 HNK), 0.93 nM (HIV-1 HTN), 0.55 nM (HIV-1 HHA), and EC90 values of 12 nM (HIV-1 KK), 5 nM (HIV-1 CTV), 12 nM (HIV-1 HKW), 28 nM in PBMC of (HIV-1 HNK), 15 nM (HIV-1 HTN), and 4 nM (HIV-1 HHA) [1]. Moreover, TAK-220 selectively inhibits HIV-1. With IC50 values of 3.12 nM against HIV-1 R5-08, 13.47 nM against HIV-1 R5-06, and 2.26 nM against HIV-1 R5-18, TAK-220 demonstrated strong inhibitory efficacy against R5 isolates. In uninfected PBMC, TAK-220 (>100 nM) is not harmful [2].
TAK-220 demonstrates potent in vitro activity as a CCR5 antagonist. In CHO cells expressing CCR5, TAK-220 inhibits the binding of MIP-1α and RANTES with IC50 values of 1.4 nM and 3.5 nM, respectively. The compound shows excellent selectivity for CCR5 over other chemokine receptors, with no effect on binding to CCR1, CCR2b, CCR3, CCR4, or CCR7. This selectivity profile makes TAK-220 a valuable tool for studying CCR5-specific signaling pathways without off-target effects on other chemokine receptors. The compound's potent antagonist activity at CCR5 is consistent with its potential utility in HIV research and in studies of inflammatory diseases. |
| ln Vivo |
TAK-220 has been evaluated in vivo for its ability to block CCR5-mediated effects. The compound is orally bioavailable, making it suitable for oral administration in animal studies. In preclinical models, TAK-220 has been shown to effectively block CCR5-dependent signaling and reduce inflammatory responses. The compound's oral bioavailability and selectivity for CCR5 make it a valuable tool for studying the role of CCR5 in HIV infection, immune cell trafficking, and inflammation. Detailed in vivo efficacy data, including specific model results and dosing regimens, are available in the primary literature. TAK-220's profile supports its utility in validating CCR5 as a therapeutic target.
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| Enzyme Assay |
The in vitro receptor binding assay for TAK-220 measures the inhibition of chemokine binding to CCR5. Membrane preparations from CHO cells expressing recombinant human CCR5 are incubated with varying concentrations of TAK-220 (typically ranging from nanomolar to micromolar) in the presence of a radiolabeled chemokine (e.g., 125I-labeled MIP-1α or RANTES). The amount of bound radioligand is measured by scintillation counting, and IC50 values are determined by fitting competition binding curves. The compound is dissolved in DMSO and diluted in assay buffer to achieve the desired final concentrations, with DMSO concentration kept constant across all wells. Appropriate positive controls (known CCR5 antagonists) and negative controls (DMSO vehicle) are included in each assay run. Selectivity is assessed by testing the compound against other chemokine receptors.
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| Cell Assay |
The in vitro cellular assay for TAK-220 measures the inhibition of CCR5-mediated signaling or chemotaxis. Cells expressing CCR5, such as CHO-CCR5 cells or primary human T cells, are treated with varying concentrations of TAK-220 or vehicle control (DMSO) prior to stimulation with chemokines such as MIP-1α or RANTES. CCR5 activation is measured by assessing downstream signaling events such as calcium mobilization (using fluorescent calcium indicators), GTPγS binding, or chemotaxis in a Boyden chamber assay. The antagonist activity of TAK-220 is quantified by measuring the inhibition of chemokine-induced signaling or cell migration. Dose-response curves are generated to determine IC50 values. The compound's effects on HIV-1 entry can also be assessed using pseudovirus or replication-competent virus entry assays.
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| Animal Protocol |
In vivo animal experiments with TAK-220 are typically conducted using mouse models of inflammation or HIV infection. TAK-220 is administered orally at various doses due to its oral bioavailability. For inflammatory models, mice may be challenged with inflammatory stimuli, and the effects of TAK-220 on immune cell infiltration and cytokine production are assessed. For HIV studies, humanized mouse models or transgenic models expressing human CCR5 may be used. The compound's ability to block CCR5-dependent effects is evaluated by measuring relevant endpoints such as inflammatory markers, viral load, or immune cell trafficking. Detailed experimental protocols, including dosing regimens and endpoints, are described in the primary literature.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) parameters for TAK-220 are not extensively documented in publicly available sources. However, TAK-220 is described as orally bioavailable, indicating that it has adequate oral absorption for in vivo studies. The compound has a molecular weight of 553.14 and a chemical formula of C31H41ClN4O3. The compound is soluble in DMSO for formulation purposes. For in vivo oral administration, TAK-220 is typically formulated using appropriate vehicles to ensure adequate solubility and stability. The compound should be stored under conditions recommended by the manufacturer to maintain stability and prevent degradation. Detailed PK parameters including half-life, clearance, volume of distribution, and maximum concentration (Cmax) are available in the primary literature and should be consulted for specific experimental planning.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for TAK-220 are not extensively documented in publicly available sources. As a research-grade compound, TAK-220 is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. The compound should be stored according to the manufacturer's recommendations to maintain stability and prevent degradation. Comprehensive toxicological profiling (e.g., LD50, maximum tolerated dose, organ-specific toxicity) is not available from the current search results and would require consultation of the primary literature or safety data sheets.
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| References |
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| Additional Infomation |
Structure in the first source
TAK-220 is a research compound developed for studying the role of CCR5 in HIV infection, immune cell trafficking, and inflammation. The compound is a potent and selective CCR5 antagonist that inhibits the binding of MIP-1α and RANTES with IC50 values of 1.4 nM and 3.5 nM, respectively. TAK-220 shows excellent selectivity for CCR5 over other chemokine receptors. The compound is orally bioavailable, making it suitable for in vivo studies. TAK-220 is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical research. The compound is available from various chemical suppliers for research purposes. Its utility lies in its ability to selectively inhibit CCR5 and probe its role in HIV pathogenesis and inflammatory diseases. |
| Molecular Formula |
C31H41CLN4O3
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|---|---|
| Molecular Weight |
553.1352
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| Exact Mass |
552.287
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| CAS # |
333994-00-6
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| Related CAS # |
333994-00-6; 674782-27-5 (TAK-220 HCl)
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| PubChem CID |
5275766
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| Appearance |
White to off-white solid powder
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| LogP |
5.259
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
39
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| Complexity |
817
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C=C(C=C1)N(CCCN2CCC(CC2)CC3=CC=C(C=C3)C(=O)N)C(=O)C4CCN(CC4)C(=O)C)Cl
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| InChi Key |
ASSJTMUEFHUKMJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H41ClN4O3/c1-22-4-9-28(21-29(22)32)36(31(39)27-12-18-35(19-13-27)23(2)37)15-3-14-34-16-10-25(11-17-34)20-24-5-7-26(8-6-24)30(33)38/h4-9,21,25,27H,3,10-20H2,1-2H3,(H2,33,38)
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| Chemical Name |
1-acetyl-N-[3-[4-[(4-carbamoylphenyl)methyl]piperidin-1-yl]propyl]-N-(3-chloro-4-methylphenyl)piperidine-4-carboxamide
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| Synonyms |
TAK220, TAK 220, TAK-220
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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 |
| 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 : ≥ 50 mg/mL (~90.39 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.52 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 25.0 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: ≥ 2.5 mg/mL (4.52 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 25.0 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: ≥ 2.5 mg/mL (4.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8079 mL | 9.0393 mL | 18.0786 mL | |
| 5 mM | 0.3616 mL | 1.8079 mL | 3.6157 mL | |
| 10 mM | 0.1808 mL | 0.9039 mL | 1.8079 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.
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