| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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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 is the CCR5 chemokine receptor, a G protein-coupled receptor that serves as a co-receptor for HIV-1 entry into host cells. Aplaviroc acts as a non-competitive allosteric antagonist, binding to CCR5 and blocking the interaction of the viral envelope protein gp120 with the receptor. This prevents HIV-1 from binding and entering T cells, thereby inhibiting viral replication. |
|---|---|
| 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 exerts potent activity against three wild-type R5 HIV-1 strains (HIV-1Ba-L, HIV-1JRFL, and HIV-1MOKW) with IC50 values of 0.1 to 0.4 nM. Aplaviroc suppresses the infectivity and replication of two HIV-1MDR variants, HIV-1MM and HIV-1JSL, at extremely low concentrations (IC50 values of 0.4 to 0.6 nM). It is a highly potent CCR5 antagonist. |
| 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, the concentration of Aplaviroc reaches the maximal concentration immediately after intraperitoneal administration and decreases rapidly. Aplaviroc (60 mg/kg, bid, daily) suppresses R5 HIV-1 viremia in hu-PBMC-NOG mice. These findings demonstrate the in vivo antiviral efficacy of Aplaviroc in a humanized mouse model of HIV-1 infection. |
| Enzyme Assay |
The CCR5 binding assay for Aplaviroc involves incubating the compound with membrane preparations from cells expressing human CCR5 and a radiolabeled CCR5 ligand (such as [¹²⁵I]-MIP-1α). 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, cells expressing CCR5 (such as T cells or CCR5-transfected cell lines) are infected with R5-tropic HIV-1 strains in the presence of varying concentrations of Aplaviroc. 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 is evaluated in hu-PBMC-NOG mice, a humanized mouse model of HIV-1 infection. Mice are engrafted with human peripheral blood mononuclear cells (PBMCs) and then infected with R5-tropic HIV-1. Aplaviroc is administered intraperitoneally at a dose of 60 mg/kg twice daily. Plasma viral load is measured by quantitative RT-PCR to assess the suppression of viremia. |
| ADME/Pharmacokinetics |
Aplaviroc is soluble in DMSO. Specific pharmacokinetic parameters (e.g., Cmax, Tmax, half-life, AUC) are not detailed in the available sources. The compound has a molecular weight of 577.71 and a molecular formula of C33H43N3O6. It is typically stored as a solid powder at -20°C.
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| Toxicity/Toxicokinetics |
Specific toxicity data for Aplaviroc 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 |
spirodikepiperazine compound; a potent, non-competitive CCR5 receptor allosteric antagonist with potent anti-HIV-1 activity. Apravilok is a CC chemokine receptor type 5 (CCR5) antagonist with anti-HIV-1 activity. Apravilok inhibits HIV-1 entry by interacting with the CCR5 co-receptor. Indications: Under investigation for the treatment of HIV infection. Mechanism of Action: GW873140 is a novel CCR5 receptor antagonist that specifically binds to human CCR5. Its binding to human CCR5 is unique in its selective inhibition of monoclonal antibody binding. CCR5 inhibitors differ from currently available HIV drugs in that they bind to the host (CCR5 receptor) cellular target, rather than to viral enzymes in cells such as CD4 cells.
Aplaviroc is a potent non-competitive CCR5 receptor allosteric antagonist with IC50 values of 0.1-0.4 nM for HIV-1Ba-L, HIV-1JRFL, and HIV-1MOKW. It suppresses R5 HIV-1 viremia in hu-PBMC-NOG mice. It is also known as AK 602. It has a molecular formula of C33H43N3O6 and a molecular weight of 577.71. |
| Molecular Formula |
C33H43N3O6
|
|---|---|
| Molecular Weight |
577.71102
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| Exact Mass |
577.315
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| Elemental Analysis |
C, 68.61; H, 7.50; N, 7.27; O, 16.62
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| CAS # |
461443-59-4
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| Related CAS # |
Aplaviroc hydrochloride; 461023-63-2
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| PubChem CID |
3001322
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| Appearance |
Solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
800.6±65.0 °C at 760 mmHg
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| Flash Point |
438.0±34.3 °C
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| Vapour Pressure |
0.0±3.0 mmHg at 25°C
|
| Index of Refraction |
1.630
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| LogP |
4.31
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
10
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| Heavy Atom Count |
42
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| Complexity |
915
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O=C(O)C1=CC=C(OC2=CC=C(CN(CC3)CCC3(N(CCCC)C([C@@H]([C@@H](C4CCCCC4)O)N5)=O)C5=O)C=C2)C=C1
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| InChi Key |
GWNOTCOIYUNTQP-FQLXRVMXSA-N
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| InChi Code |
InChI=1S/C33H43N3O6/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)/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
|
| Synonyms |
GSK-873140; AK 602; GW873140A; ONO-4128; GSK 873140; AGW 873140; ONO 4128; K602; GW-873140; GSK873140; AK 602; AK-602; GW873140; ONO4128; Aplaviroc hydrochloride
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| HS Tariff Code |
2934.99.03.00
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7310 mL | 8.6549 mL | 17.3097 mL | |
| 5 mM | 0.3462 mL | 1.7310 mL | 3.4619 mL | |
| 10 mM | 0.1731 mL | 0.8655 mL | 1.7310 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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