Maraviroc

Category	Human immunodeficiency Virus (HIV)
CAS	376348-65-1
Description	Maraviroc is a selective CCR5 antagonist.

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Product Information

Synonyms	Maraviroc; Selzentry; Celsentri; UK-427857; UK-427,857; Pfizer Brand of maraviroc; Selzentry; UK-427,857; UK-427857; 4,4-Difluoro-N-[(1S)-3-[(3-exo)-3-[3-methyl-5-(1-methylethyl-d6)-4H-1,2,4-triazol-4-yl]-8-azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl]cyclohexanecarboxamide; UK 427857-d6;
Molecular Weight	513.67
Molecular Formula	C29H41F2N5O
Canonical SMILES	O=C(C1CCC(CC1)(F)F)N[C@H](c1ccccc1)CCN1C2CCC1CC(C2)n1c(C)nnc1C(C)C
InChI	CC1=NN=C(N1C2CC3CCC(C2)N3CCC(C4=CC=CC=C4)NC(=O)C5CCC(CC5)(F)F)C(C)C
InChIKey	GSNHKUDZZFZSJB-HLMSNRGBSA-N
Melting Point	197-198(dec.)
Purity	0.9995
Density	1.3±0.1 g/cm3
Solubility	Soluble to 75 mM in DMSO and to 100 mM in ethanol
Appearance	White to Off-White Solid
Shelf Life	24 months.
Storage	Store at +4°C
Animal Admin	Preclinical pharmacokinetic studies are carried out with maraviroc following a single intravenous and oral administration to both male Sprague-Dawley rats and male beagle dogs (0.5 mg/kg i.v. and 2 mg/kg p.o; n=4). Plasma samples are taken for up to 24 h postdose, and the concentrations of unchanged maraviroc are determined using a specific high-performance liquid chromatography-tandem mass spectrum assay. Mice Splenocytes are collected from 6-10 week old CCR5-/- mice or wild-type controlmice (n=8 per group) and naive CD4+ CD45RBhigh T-cells are isolated by cell sorting. A total of 3×105 CD45RBhigh cells are then injected intravenously into Rag1-/- mice that are subsequently weighed and assessed for fecal score every 20 days to evaluate IBD development.
Complexity	751
Exact Mass	513.32791727
Index Of Refraction	1.628
In Vitro	Maraviroc (UK-427857) is a selective CCR5 antagonist with potent anti-human immunodeficiency virus type 1 (HIV-1) activity. Maraviroc 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. Maraviroc (UK-427857) is active (IC90) at low nanomolar concentrations against HIV-1 Ba-L (a lab-adapted R5 strain) when measured in a 5-day antiviral assay using either isolated multiple (pooled) donor PBMC (IC90, 3.1 nM), single-donor PBMC (IC90, 1.8 nM) or PM-1 cells (IC90, 1.1 nM).
In Vivo	Clearance values are moderate to high in both rat and dog species following i.v. administration (74 and 21 mL/min/kg, respectively). Maraviroc also has a moderate volume of distribution in both species (4.3 to 6.5 liters/kg). The half-life values of maraviroc are 0.9 h in the rat and 2.3 h in the dog. Following oral administration (2 mg/kg) to the dog, the Cmax(256 ng/mL) occurs 1.5 h. post-dose, and the bioavailability is 40%. For the rat, investigation of the concentrations obtain in the portal vein following oral administration indicated that approximately 30% of the administered dose is absorbed from the intestinal tract. In the DSS/TNBS colitis and in the transfer model, Maraviroc attenuates development of intestinal inflammation by selectively reducing the recruitment of CCR5 bearing leukocytes.
PSA	63.05000
Target	MIP-1α-CCR5: 3.3 nM (IC50, in HEK-293 cell membrane) RANTES-CCR5: 5.2 nM (IC50, in HEK-293 cell membrane) MIP-1β-CCR5: 7.2 nM (IC50, in HEK-293 cell membrane) HIV-1 (Ba-L): 1.1 nM (IC50, in PM-1 cells)
XLogP3-AA	5.1