TAK-220 (TAK220), a novel 1,4-disubstituted piperidine/piperazine, is a potent, selective and orally bioavailable CCR5 antagonist with IC50s of 3.5 nM and 1.4 nM for inhibition on the binding of RANTES and MIP-1α to CCR5, respectively. It shows no effect on the binding to CCR1, CCR2b, CCR3, CCR4, or CCR7; TAK-220 also selectively inhibits HIV-1, with EC50s 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), and 0.55 nM (HIV-1 HHA), and EC90s of 12 nM (HIV-1 KK), 5 nM (HIV-1 CTV), 12 nM (HIV-1 HKW), 28 nM (HIV-1 HNK), 15 nM (HIV-1 HTN), and 4 nM (HIV-1 HHA) in PBMCs.
Physicochemical Properties
| Molecular Formula | C31H41CLN4O3 |
| Molecular Weight | 553.1352 |
| Exact Mass | 552.287 |
| CAS # | 333994-00-6 |
| Related CAS # | 333994-00-6; 674782-27-5 (TAK-220 HCl) |
| PubChem CID | 5275766 |
| Appearance | White to off-white solid powder |
| LogP | 5.259 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 39 |
| Complexity | 817 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | ASSJTMUEFHUKMJ-UHFFFAOYSA-N |
| 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) |
| Chemical Name | 1-acetyl-N-[3-[4-[(4-carbamoylphenyl)methyl]piperidin-1-yl]propyl]-N-(3-chloro-4-methylphenyl)piperidine-4-carboxamide |
| Synonyms | TAK220, TAK 220, TAK-220 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| 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]. |
| References |
[1]. Highly potent inhibition of human immunodeficiency virus type 1 replication by TAK-220, an orally bioavailable small-molecule CCR5 antagonist. Antimicrob Agents Chemother. 2005 Aug;49(8):3474-82. [2]. TAK-220, a novel small-molecule CCR5 antagonist, has favorable anti-human immunodeficiency virus interactions with other antiretrovirals in vitro. Antimicrob Agents Chemother. 2005 Aug;49(8):3483-5. |
Solubility Data
| Solubility (In Vitro) | DMSO : ≥ 50 mg/mL (~90.39 mM) |
| 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. 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. 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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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 |