[CAS NO. 333994-00-6] TAK-220
PRODUCTS SPECIFICATIONS [333994-00-6]
DESCRIPTION [333994-00-6]
Overview
| MDL | MFCD28502079 |
|---|---|
| Molecular Weight | 553.14 |
| Molecular Formula | C31H41ClN4O3 |
| SMILES | O=C(C1CCN(C(C)=O)CC1)N(CCCN2CCC(CC3=CC=C(C(N)=O)C=C3)CC2)C4=CC=C(C)C(Cl)=C4 |
1 Publications Citing Use of MCE
Summary
TAK-220 is a selective and orally bioavailable CCR5 antagonist, with IC 50 s of 3.5 nM and 1.4 nM for inhibition on the binding of RANTES and MIP-1α to CCR5 , respectively, but shows no effect on the binding to CCR1 , CCR2b, CCR3 , CCR4 , or CCR7 ; TAK-220 also selectively inhibits HIV-1 , with EC 50 s 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 EC 90 s 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.
IC50 & Target
|
MIP-1α-CCR5 1.4 nM (IC 50 , in CHO cells) |
RANTES-CCR5 3.5 nM (IC 50 , in CHO cells) |
HIV-1 (HHA) 0.55 nM (EC 50 , in PBMCs) |
HIV-1 (CTV) 0.72 nM (EC 50 , in PBMCs) |
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|
HIV-1 (HTN) 0.93 nM (EC 50 , in PBMCs) |
HIV-1 (KK) 1.2 nM (EC 50 , in PBMCs) |
HIV-1 (HKW) 1.7 nM (EC 50 , in PBMCs) |
HIV-1 (HNK) 1.7 nM (EC 50 , in PBMCs) |
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HIV-1 (HHA) 4 nM (EC90, in PBMCs) |
HIV-1 (CTV) 5 nM (EC90, in PBMCs) |
HIV-1 (KK) 12 nM (EC90, in PBMCs) |
HIV-1 (HKW) 12 nM (EC90, in PBMCs) |
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|
HIV-1 (HTN) 15 nM (EC90, in PBMCs) |
HIV-1 (HNK) 28 nM (EC90, in PBMCs) |
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In Vitro
TAK-220 is a selective CCR5 antagonist, with IC 50 s of 3.5 nM and 1.4 nM for inhibition on the binding of RANTES and MIP-1α to CCR5 in CHO cells, respectively, but shows no effect on the binding to CCR1, CCR2b, CCR3, CCR4, or CCR7. TAK-220 (0-1000 nM) interacts with CCR5 but not with RANTES and inhibits the CCR5-mediated Casup>2+ signaling. TAK-220 inhibits R5 HIV-1 (JR-FL) envelope-mediated membrane fusion, with an IC 50 value of 0.42 nM, but does not alter X4 HIV-1 (HXB2) envelope-mediated membrane fusion. TAK-220 also selectively inhibits HIV-1, with EC 50 s 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 EC 90 s 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 [1] . TAK-220 shows potent inhibitory activity against the R5 isolates, with IC 50 s 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 (>100 nM) has no toxicity in uninfected PBMCs [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
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
DMSO : ≥ 50 mg/mL ( 90.39 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 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 |
References
- [1] Takashima K, et al. 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] Tremblay CL, et al. 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.