Maraviroc

Catalog No.S2003 Batch:S200305

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Technical Data

Formula

C29H41F2N5O

Molecular Weight 513.67 CAS No. 376348-65-1
Solubility (25°C)* In vitro DMSO 100 mg/mL (194.67 mM)
Ethanol 100 mg/mL (194.67 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Maraviroc is a CCR5 antagonist for MIP-1α, MIP-1β and RANTES with IC50 of 3.3 nM, 7.2 nM and 5.2 nM in cell-free assays, respectively. Maraviroc is used in the treatment of HIV infection.
Targets
CCR5 [3]
(Cell-free assay)
MIP-1α [1]
(Cell-free assay)
RANTES [1]
(Cell-free assay)
MIP-1β [1]
(Cell-free assay)
3.3 nM 5.2 nM 7.2 nM
In vitro

Maraviroc inhibits MIP-1β-stimulated γ-S-GTP binding to HEK-293 cell membranes, indicating its ability to inhibit chemokine-dependent stimulation of GDP-GTP exchange at the CCR5/G protein complex. Maraviroc also inhibits the downstream event of chemokine-induced intracellular calcium redistribution, with IC50s ranging from 7 to 30 nM obtained against MIP-1β, MIP-1α and RANTES. In the same experiments, Maraviroc does not trigger release of intracellular calcium at concentrations up to 10 μM, indicating that it is devoid of CCR5 agonist activity. Consistent with this, Maraviroc fails to induce CCR5 internalization. Maraviroc is active at low nanomolar concentrations against HIV-1 Ba-L. Maraviroc inhibits all 200 pseudotyped viruses with a geometric mean IC90 of 13.7 nM. [1] At concentrations >1000 times the 50% inhibitory concentration, maraviroc did not inhibit other chemokine receptors (CCR1, 2, 3, 4, 7, and 8; CXCR1 and 2) to a clinically relevant degree[3].

In vivo

The half-life values of Maraviroc are 0.9 hour in the rat and 2.3 hours in the dog. Following oral administration (2 mg/kg) to the dog, the Cmax (256 ng/ml) occurred 1.5 hours post-dose, and the bioavailability is 40%. For the rat, approximately 30% of the administered dose is absorbed from the intestinal tract. [1] Female RAG-hu mice are challenged vaginally with HIV-1 an hour after intravaginal application of the Maraviroc gel. Maraviroc gel treated mice are fully protected against vaginal HIV-1 challenge in contrast to placebo gel treated mice which all became infected. Vaginal administration of Maraviroc fully protects mice against HIV-1 vaginal challenge. While there is a clear pattern of CD4 T cell decline in placebo-gel treated and viral challenged mice, their levels are stable in mice receiving Maraviroc gel. [2]

Protocol (from reference)

Kinase Assay:

[1]

  • Inhibition of chemokine binding to CCR5

    Binding of 125I-labeled MIP-1α, MIP-1β, and RANTES to CCR5 is measured using intact HEK-293 cells stably expressing the receptor or membrane preparations thereof. Briefly, cells are resuspended in binding buffer (50 mM HEPES containing 1 mM CaCl2, 5 mM MgCl2, and 0.5% bovine serum albumin [BSA] and adjusted to pH 7.4) to a density of 2 × 106 cells/ml. For membrane preparations, phosphate-buffered saline (PBS)-washed cells are resuspended in lysis buffer (20 mM HEPES, 1 mM CaCl2, 1 tablet COMPLETE per 50 mL, pH 7.4) prior to homogenization in a Polytron hand-held homogenizer, ultracentrifugation (40,000× g for 30 min), and resuspension in binding buffer to a protein concentration of 0.25 mg/mL (12.5 μg of membrane protein is used in each well of a 96-well plate). 125I-radiolabeled MIP-1α, MIP-1β, and RANTES are prepared and diluted in binding buffer to a final concentration of 400 pM in the assay. Maraviroc dilutions are added to each well to a final volume of 100 μL, the assay plates incubate for 1 hour, and the contents filter through preblocked and washed Unifilter plates which are counted following overnight drying.

Cell Assay:

[1]

  • Cell lines

    PHA-stimulated PBMC or PM-1 cells

  • Concentrations

    0-1 μM

  • Incubation Time

    5 days or 7 days

  • Method

    Drug susceptibility assays are performed in 24-well tissue culture plates. Duplicate eight-point dilution series of Maraviroc are prepared in DMSO and medium to yield a final DMSO concentration of 0.1% (vol/vol) in the assay. PHA-stimulated PBMC or PM-1 cells are infected with virus for 1 hour at 37 °C. Cells are subsequently washed once, and 3.6 × 105 PBMC or 2.0 × 105 PM-1 cells are added to each well of assay plates containing diluted Maraviroc. Plates are incubated for 5 days (lab-adapted strains) or 7 days (primary isolates) at 37 °C in a humidified 5% CO2 (vol/vol) atmosphere.

Animal Study:

[2]

  • Animal Models

    Humanized BALB/c-Rag2−/−γc−/− and BALB/c-Rag1−/−γc−/− (RAG-hu) mice

  • Dosages

    ~64 μg

  • Administration

    A 25 μL volume of the gel formulation is carefully applied in to the vaginal vault of mice.

Customer Product Validation

Data from [Cancer Res, 2012, 72(15), 3839-50]

, 2010, Dr. Johanna Weiss of University Hospital Heidelberg

Data from [Data independently produced by , , Clin Cancer Res, 2018, 78(7):1657-1671]

Data from [Data independently produced by , , Cancer Res, 2018, 78(7):1657-1671]

Selleck's Maraviroc has been cited by 48 publications

Microglial-to-neuronal CCR5 signaling regulates autophagy in neurodegeneration [ Neuron, 2023, S0896-6273(23)00268-4] PubMed: 37105172
CCL5/CCR5-mediated peripheral inflammation exacerbates blood‒brain barrier disruption after intracerebral hemorrhage in mice [ J Transl Med, 2023, 21(1):196] PubMed: 36918921
Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes [ Neural Regen Res, 2023, 18(1):141-149] PubMed: 35799534
Acute antagonism in three-drug combinations for vaginal HIV prevention in humanized mice [ Sci Rep, 2023, 13(1):4594] PubMed: 36944714
Revealing viral and cellular dynamics of HIV-1 at the single-cell level during early treatment periods [ Cell Rep Methods, 2023, 3(6):100485] PubMed: 37426753
Cancer-associated fibroblasts facilitate premetastatic niche formation through lncRNA SNHG5-mediated angiogenesis and vascular permeability in breast cancer [ Theranostics, 2022, 12(17):7351-7370] PubMed: 36438499
Tumor bud-derived CCL5 recruits fibroblasts and promotes colorectal cancer progression via CCR5-SLC25A24 signaling [ J Exp Clin Cancer Res, 2022, 41(1):81] PubMed: 35241150
The analgesic properties of Yu-Xue-Bi tablets in the inflammatory pain mice: By the inhibition of CCL3-mediated macrophage transmigration into the spinal cord [ J Ethnopharmacol, 2022, 289:115051] PubMed: 35101573
Imatinib Mesylate Exerted Antitumor Effect by Promoting Infiltration of Effector T Cells in Tumor [ Biol Pharm Bull, 2022, 45(1):34-41] PubMed: 34980779
Pericytes augment glioblastoma cell resistance to temozolomide through CCL5-CCR5 paracrine signaling [ Cell Res, 2021, 10.1038/s41422-021-00528-3] PubMed: 34239070

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.