Ancriviroc
Ancriviroc (SCH-351125) is an orally active CCR5 antagonist with an IC50 value of 13 nM against hCCR5. Ancriviroc specifically binds to hCCR5, blocks ligand-induced signal transduction, calcium influx, GTPγS binding, chemotaxis, ligand binding, and HIV-1 entry, induces conformational changes in CCR5, and inhibits infection and replication of R5-tropic HIV-1.
For research use only. We do not sell to patients.
- CAS No.: 370893-06-4
- Formula: C28H37BrN4O3
- Molecular Weight:557.52
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
All Calcium Channel Isoforms
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Biological Activity
Description
IC50 & Target
[1]|
HIV-1 |
CCR5 13 nM (IC50) |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| U-87MG ATCC | IC50 |
0.6 nM
Compound: 1
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Concentration required to inhibit the entry of HIV-1 reporter virus (ADA) into U-87 cells by 50%
Concentration required to inhibit the entry of HIV-1 reporter virus (ADA) into U-87 cells by 50%
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[PMID: 12086500] |
In Vitro
Ancriviroc (0.3-10 nM; 1 h) potently inhibits the binding of RANTES to CCR5 expressed on the membrane of CHO cells, with a Ki value of 2.9 nM[1].
Unlabeled Ancriviroc (10 μM, 2 h) binds to CCR5 on B550 cells with high affinity, with a Kd value of 9.27 nM and a Bmax value of 1.98 × 10-4 fmol/cell[1].
Ancriviroc inhibits agonist-induced CCR5 activation in CHO-CCR5 cell membranes, with an IC50 of approximately 16 nM for MIP-1β-induced [35S]GTPγS binding[1].
Ancriviroc (1 h) inhibits the entry of R5 envelope-pseudotyped HIV-1 into U87-CD4-CCR5 cells, with a mean IC50 of 0.69 nM[1].
Ancriviroc (SCH-351125) (at concentrations up to 10000 nM for 3 h) potently inhibits the binding of [125I]-CCL3 to membranes of B300-19 cells expressing human CCR5, with an IC50 of 13 nM; it shows no activity against mouse CCR5 even at concentrations as high as 10000 nM[2].
Ancriviroc (administered 1 min prior to CCL3) inhibits CCL3-induced intracellular Ca2+ elevation in CCR5-expressing B300-19 cells, with an IC50 of 81 nM; it shows no activity against mouse CCR5 even at concentrations as high as 10000 nM[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:B550 cells (BayF3 murine pro-B cell line stably expressing human CCR5)
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Concentration:0.01 nM-1 μM
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Incubation Time:1.5 h
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Result:Inhibited MIP-1β-induced chemotaxis of B550 cells with an IC50 of less than 1 nM, and had no chemoattractant activity itself.
Parmacokinetics
In Vivo
Ancriviroc (0.01-10 mg/kg; p.o.; single administration) dose-dependently occupies CCR5 receptors in CCR5 transgenic mice, with an ED50 of 0.10 mg/kg, and achieves nearly complete receptor occupancy at doses of 1 mg/kg and 10 mg/kg[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C.B-17 scid/scid (HIV-1 infection model via implantation of human fetal thymus and liver)[1]
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Dosage:3 mg/kg per day; 10 mg/kg per day; 30 mg/kg per day
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Administration:p.o.; twice daily; 28 days
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Result:Reduced p24 levels and viral RNA significantly relative to untreated mice at 3 mg/kg per day and 10 mg/kg per day.
Achieved undetectable p24 antigen and reduced viral RNA by 3.6 log10 compared with untreated mice at 30 mg/kg per day.
Reduced MHC class I expression on implant cells in a dose-dependent manner compared with untreated mice.
Chemical Information
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CAS No. 370893-06-4
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Molecular Weight 557.52
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Formula C28H37BrN4O3
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SMILES
CCO/N=C(C1=CC=C(C=C1)Br)/C2CCN(C3(CCN(CC3)C(C4=C([N+]([O-])=CC=C4C)C)=O)C)CC2
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Synonyms
SCH-351125
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Research Protocol for Infectious Diseases
Infectious-disease experiments test how pathogens interact with host barriers, innate immune receptors, inflammatory signaling, pathogen replication, and tissue injury; pattern-recognition receptors such as TLRs, RIG-I-like receptors, NOD-like receptors, and inflammasomes detect microbial molecules and activate NF-κB, interferon, and cytokine responses. The central hypothesis is that infection severity reflects the balance between pathogen burden and host response: protective inflammation restricts pathogen growth, whereas excessive or mislocalized inflammation contributes to tissue damage and disease phenotype. Unresolved questions include which host pathways are protective versus pathogenic, why some infection models fail to translate to human disease, and which combined readouts best predict clinically relevant infection outcomes.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Cell migration
Cell migration is a method that plays an important role in wound healing, cell differentiation, embryonic development, etc.
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Chemotaxis Gradient Chamber Assay 1
The chemotaxis gradient chamber assay is based on the principle of observing directional cell migration in response to a stable, linear or quasi-linear concentration gradient of a chemoattractant formed between two fluid reservoirs separated by a narrow observation chamber. Cells placed within the chamber respond to the gradient by polarized movement toward higher chemoattractant concentrations, allowing quantification of chemotactic behavior in real time under microscopy. The classic Zigmond chamber design enables simultaneous visualization of gradient formation and individual cell trajectories, making it suitable for studying leukocyte chemotaxis and other motile cell types in vitro.
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Under-Agarose Cell Migration Assay
The under-agarose cell migration assay is a classical in vitro chemotaxis method designed to evaluate directed cell movement through a semi-solid agarose matrix toward soluble chemoattractant gradients, enabling visualization and quantification of leukocyte or motile cell migration in a confined 2D-like environment. In this system, cells and chemoattractants are placed in separate wells cut into an agarose gel, allowing diffusion-driven gradient formation that guides directional migration, which is typically assessed by measuring migration distance, cell morphology changes, and accumulation toward the chemoattractant source. This assay has been widely used to study neutrophil and leukocyte chemotaxis as a simple alternative to filter-based migration systems and allows direct microscopic observation of migrating cells under near-physiological confinement conditions.
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Transwell/Boyden Chamber Migration Assay
The Transwell/Boyden chamber migration assay measures cell movement through a porous membrane separating an upper and lower chamber, usually after a chemoattractant gradient is established by placing cells in the upper chamber and chemoattractant-containing medium in the lower chamber. The readout is generated by quantifying cells that traverse the membrane and appear on the lower membrane surface or in the lower chamber, depending on whether the cell type is adherent or non-adherent. This assay reflects chemotactic or haptotactic migration rather than matrix invasion unless an extracellular-matrix barrier is added to the membrane.
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Ca2+ Staining Technique
Ca2+ staining is an experimental technique that utilizes specific fluorescent probes (such as Fluo-4 AM, Fura-2, etc.) to qualitatively or quantitatively detect dynamic changes in intracellular Ca2+ concentrations; this is achieved by monitoring the changes in fluorescent signals generated when these probes bind to free intracellular calcium ions. The underlying principle relies primarily on the presence of chelating groups within the probe's molecular structure that possess high affinity for calcium ions.
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Chemotaxis Gradient Chamber Assay 2
Chemotaxis gradient chamber assays measure directional cell migration in response to a soluble chemical gradient by imaging cells as they move across a defined observation region; the readout is generated from time-lapse cell trajectories, displacement toward the gradient, forward migration index, trajectory plots, rose/polar plots, and statistical tests of non-random directionality. The Dunn chamber is a direct-viewing glass chamber in which cells migrate across a bridge between control and chemoattractant wells, allowing observation of cells in a linear concentration gradient; related direct-viewing formats include the Insall chamber, which supports defined unidirectional gradients and high numerical-aperture microscopy, and the μ-Slide Chemotaxis chamber, which supports long-term live-cell imaging and gradient characterization with fluorescent dye.
Purity & Documentation
References
[1]. Strizki JM, et al. SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo. Proc Natl Acad Sci U S A. 2001;98(22):12718-12723. [Content Brief]
[2]. Saita Y, et al. Transgenic mouse expressing human CCR5 as a model for in vivo assessments of human selective CCR5 antagonists. Eur J Pharmacol. 2005;518(2-3):227-233. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)