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Maraviroc

(CAS No:376348-65-1)

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.

CAS No:376348-65-1

Molecular Weight(MW):513.67

Purity:99.00%

Specification:500MG;1G;5G;10G;50G;100G

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COA	MSDS	HPLC	NMR

ChemicalInfomation

CAS No:	376348-65-1
Molecular formula(MF)	C₂₉H₄₁F₂N₅O
Molecular Weight(MW):	513.67
Alias	Maraviroc(UK427857); 4,4-Difluoro-N-[(1S)-3-[(1R,5S)-3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-phenylpropyl]cyclohexane-1-carboxamide; maroviroc; 4,4-Difluoro-N-{(1S)-3-[3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl}cyclohexanecarboxamide; Maraviroc(Selzentry); 4,4-difluoro-N-[(1S)-3-[(1R,3R,5S)-3-[3-Methyl-5-(propan-2-yl)-4H-1,2,4-triazol-4-yl]-8-azabicyclo[3.2.1]octan-8-yl]-1-phenylpropyl]cyclohexane-1-carboxaMide; Celsentri

Solubility

In vitro	DMSO	100 mg/mL (194.67 mM)
	Ethanol	100 mg/mL (194.67 mM)
	Water	<1 mg/mL
In vivo	2% DMSO+corn oil	10mg/mL

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.

Targets

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]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
HeLa-P4 cells	Function assay		20 days	Antagonist activity at CCR5 receptor expressed in HeLa-P4 cells co-expressing CD4 assessed as inhibition of infusion to HIV gp120 expressed in CHO-tat10 cells after 20 hrs by cell-cell fusion assay, IC50=0.2 nM	21128663
rhesus monkey Chem-1 cell	Function assay		120 mins	Displacement of [125I]-MIP-1alpha from CCR5 in rhesus monkey Chem-1 cell membranes after 120 mins by liquid scintillation counting analysis, Ki=0.24 nM	23682308
human TZM-bl cells	Function assay		48 h	Antagonist activity against CCR5 receptor in human TZM-bl cells assessed as inhibition of HIV-1 MGC26-induced cell-cell fusion between viral envelope protein expressing human HEK293 cells to TZM-bl cells after 48 hrs by luciferase reporter gene assay, IC50=0.37 nM	24563723
CHO cells	Function assay		2 h	Displacement of [128I]RANTES from human CCR5 receptor coexpressed with Galphai6 in CHO cells after 2 hrs by scintillation counting, IC50=1.4 nM	20137937
HOS cells	Function assay			Antiviral activity against HIV1 Ba-L infected in HOS cells assessed as inhibition of viral infection, IC50=2 nM	19664920
HEK293 cells	Function assay			Inhibition of human MATE1-mediated ASP+ uptake expressed in HEK293 cells after 1.5 mins by fluorescence assay, IC50=17.3 Îm	23241029
human astrocytes	Function assay	100 nM	30 to 60 mins	Binding affinity to CCR5/MOR in human astrocytes assessed as inhibition of R5 HIV-1 SF162 infection by measuring Tat protein expression at 100 nM preincubated for 30 to 60 mins followed by viral infection measured after 18 hrs by luciferase reporter gene assay	23682308

... Click to View More Cell Line Experimental Data

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]