| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
HIV-1Ba-L ( IC50 = 0.4 nM ); HIV-1JRFL ( IC50 = 0.1 nM ); HIV-1MOKW ( IC50 = 0.2 nM ); CCR5
The primary target of Aplaviroc HCl is the CCR5 chemokine receptor. Aplaviroc acts as a CCR5 antagonist, blocking the interaction of the HIV-1 envelope protein gp120 with the CCR5 co-receptor. By inhibiting HIV-1 entry via the CCR5 co-receptor interaction, Aplaviroc HCl prevents viral infection of target cells. The compound is a potent CCR5 entry inhibitor. |
|---|---|
| ln Vitro |
Aplaviroc exhibits strong efficacy against three wild-type R5 HIV-1 strains: HIV-1Ba-L, HIV-1JRFL, and HIV-1MOKW, With IC50 values ranging from 0.1 to 0.4 nM. Two previously reported CCR5 inhibitors, E921/TAK-779 and AK671/SCH-C, are significantly less potent than apiverroc. In two HIV-1MDR variants, HIV-1MM and HIV-1JSL, apivirofoc inhibits replication and infectivity at incredibly low concentrations (IC50 values of 0.4 to 0.6 nM). High affinity binding of plaviroc occurs with CCR5. Kd values for Aplaviroc, E913, E921/TAK-779, and AK671/SCH-C are 2.9±1.0, 111.7±3.5, 32.2±9.6, and 16.0±1.5 nM, respectively, based on the results calculated. At a 2.7 nM IC50, apivermico effectively inhibits the binding of rgp120/sCD4 to CCR5. These findings imply that the strong action of Aplaviroc against R5 HIV-1 originates from its highly selective binding to ECL2B and/or its surrounding regions, which inhibits gp120/CD4 binding to CCR5[1].
In vitro, Aplaviroc HCl exerts potent activity against HIV-1 with IC50 values of 0.1-0.4 nM for HIV-1Ba-L, HIV-1JRFL, and HIV-1MOKW. As the hydrochloride salt of Aplaviroc, it is expected to have the same antiviral activity as the free base. It is a potent CCR5 antagonist commonly used to dissect HIV entry pathways involving chemokine receptor utilization. |
| ln Vivo |
Aplaviroc (AK602, 60 mg/kg, bid, daily) suppresses R5 HIV-1 viremia in hu-PBMC-NOG mice[2].
Immediately following intraperitoneal administration, the concentration of Aplaviroc (AK602) reached its maximum concentration and rapidly declined[2]. In vivo, Aplaviroc HCl is used in research on HIV entry and CCR5-mediated signaling. The hydrochloride salt form enhances the solubility of the compound for formulation and administration. Specific in vivo efficacy data for Aplaviroc HCl are not detailed in the available sources, but the free base Aplaviroc has demonstrated in vivo antiviral activity in hu-PBMC-NOG mice. |
| Enzyme Assay |
The CCR5 binding assay for Aplaviroc HCl involves incubating the compound with membrane preparations from cells expressing human CCR5 and a radiolabeled CCR5 ligand. After incubation, bound and free ligands are separated by filtration, and the radioactivity is counted. The IC50 for displacement of the radioligand is calculated from the competition curve. Functional antagonism is assessed using calcium mobilization or chemotaxis assays.
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| Cell Assay |
To evaluate the cellular activity of Aplaviroc HCl, cells expressing CCR5 are infected with R5-tropic HIV-1 strains in the presence of varying concentrations of Aplaviroc HCl. Viral replication is measured by quantifying p24 antigen levels in the culture supernatant using ELISA. The IC50 for inhibition of viral replication is calculated. The compound's ability to inhibit HIV-1 entry can also be assessed using single-cycle infection assays with pseudotyped viruses.
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| Animal Protocol |
hu-PBMC-NOG mice
60 mg/kg Single intraperitoneal administration, bid, daily The in vivo efficacy of Aplaviroc HCl is evaluated in humanized mouse models of HIV-1 infection, such as hu-PBMC-NOG mice. Mice are engrafted with human PBMCs and infected with R5-tropic HIV-1. Aplaviroc HCl is administered intraperitoneally at various doses. Plasma viral load is measured by quantitative RT-PCR to assess the suppression of viremia. |
| ADME/Pharmacokinetics |
Aplaviroc HCl is soluble in DMSO at 200 mg/mL (325.64 mM). For in vivo studies, it can be formulated in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline at ≥12.5 mg/mL. Specific pharmacokinetic parameters are not detailed. The compound has a molecular weight of 614.17 and a molecular formula of C33H44ClN3O6.
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| Toxicity/Toxicokinetics |
Specific toxicity data for Aplaviroc HCl are not provided in the available sources. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. The compound is a potent CCR5 antagonist, and its toxicity profile would be expected to reflect its mechanism of action. Standard safety precautions should be followed when handling this compound.
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| References |
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| Additional Infomation |
Aplaviroc hydrochloride is the hydrochloride form of Aplaviroc, a CC chemokine receptor type 5 (CCR5) antagonist with anti-HIV-1 activity. Aplaviroc inhibits HIV-1 invasion by interacting with the CCR5 co-receptor.
See also: Aplaviroc (note moved to). Aplaviroc HCl is the hydrochloride salt of Aplaviroc (AK 602), a CCR5 antagonist with IC50 values of 0.1-0.4 nM for HIV-1Ba-L, HIV-1JRFL, and HIV-1MOKW. It is also known as GW873140A, AK-602 hydrochloride, and ONO-4128. It is a CCR5 entry inhibitor for the potential treatment of HIV infection. It has a molecular formula of C33H44ClN3O6 and a molecular weight of 614.17. |
| Molecular Formula |
C33H44CLN3O6
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|---|---|
| Molecular Weight |
614.171968460083
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| Exact Mass |
613.292
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| Elemental Analysis |
C, 64.54; H, 7.22; Cl, 5.77; N, 6.84; O, 15.63
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| CAS # |
461023-63-2
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| Related CAS # |
Aplaviroc; 461443-59-4
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| PubChem CID |
6918686
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| Appearance |
White to off-white solid powder
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| LogP |
5.533
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
43
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| Complexity |
915
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CCCCN1C(=O)C(NC(=O)C12CCN(CC2)CC3=CC=C(C=C3)OC4=CC=C(C=C4)C(=O)O)C(C5CCCCC5)O.Cl
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| InChi Key |
QNNBMSGFNQRUEH-PQQSRXGVSA-N
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| InChi Code |
InChI=1S/C33H43N3O6.ClH/c1-2-3-19-36-30(38)28(29(37)24-7-5-4-6-8-24)34-32(41)33(36)17-20-35(21-18-33)22-23-9-13-26(14-10-23)42-27-15-11-25(12-16-27)31(39)40;/h9-16,24,28-29,37H,2-8,17-22H2,1H3,(H,34,41)(H,39,40);1H/t28-,29-;/m1./s1
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| Chemical Name |
4-[4-[[(3R)-1-butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-2,5-dioxo-1,4,9-triazaspiro[5.5]undecan-9-yl]methyl]phenoxy]benzoic acid;hydrochloride
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| Synonyms |
GW873140A; GW 873140; GW-873140; GW873140; ONO-4128; AK-602; AK602; AK 602; ONO 4128; ONO4128; Aplaviroc hydrochloride
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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: ~200 mg/mL (~325.6 mM)
H2O: < 0.1 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 12.5 mg/mL (20.35 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 125.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 12.5 mg/mL (20.35 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 125.0 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: ≥ 12.5 mg/mL (20.35 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 | 1.6282 mL | 8.1411 mL | 16.2821 mL | |
| 5 mM | 0.3256 mL | 1.6282 mL | 3.2564 mL | |
| 10 mM | 0.1628 mL | 0.8141 mL | 1.6282 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00076284 | Completed | Drug: GW873140 | HIV Infections | National Institute of Allergy and Infectious Diseases (NIAID) |
January 2004 | Phase 2 |
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