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Details

Stereochemistry ABSOLUTE
Molecular Formula C29H41F2N5O
Molecular Weight 513.6655
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Maraviroc

SMILES

CC(C)C1=NN=C(C)N1[C@H]2C[C@@H]3CC[C@H](C2)N3CC[C@H](NC(=O)C4CCC(F)(F)CC4)C5=CC=CC=C5

InChI

InChIKey=GSNHKUDZZFZSJB-QYOOZWMWSA-N
InChI=1S/C29H41F2N5O/c1-19(2)27-34-33-20(3)36(27)25-17-23-9-10-24(18-25)35(23)16-13-26(21-7-5-4-6-8-21)32-28(37)22-11-14-29(30,31)15-12-22/h4-8,19,22-26H,9-18H2,1-3H3,(H,32,37)/t23-,24+,25-,26-/m0/s1

HIDE SMILES / InChI

Molecular Formula C29H41F2N5O
Molecular Weight 513.6655
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Maraviroc (UK-427,857; brand-named Selzentry, or Celsentri outside the U.S) is a selective CCR5 antagonist with potent anti-human immunodeficiency virus type 1 (HIV-1) activity and favorable pharmacological properties. Maraviroc is the product of a medicinal chemistry effort initiated following identification of an imidazopyridine CCR5 ligand from a high-throughput screen of the Pfizer compound file. Selzentry, in combination with other antiretroviral agents, is indicated for adult patients infected with only CCR5-tropic HIV-1. This indication is based on analyses of plasma HIV-1 RNA levels in two controlled trials of SELZENTRY in treatment-experienced subjects and one trial in treatment-naive subjects. Maraviroc selectively binds to the human chemokine receptor CCR5 present on the cell membrane, preventing the interaction of HIV-1 gp120 and CCR5 necessary for CCR5-tropic HIV-1 to enter cells. CXCR4-tropic and dual-tropic HIV-1 entry is not inhibited by maraviroc. Antiviral Activity in Cell Culture Maraviroc inhibits the replication of CCR5-tropic laboratory strains and primary isolates of HIV-1 in models of acute peripheral blood leukocyte infection. The mean EC50 value (50% effective concentration) for maraviroc against HIV-1 group M isolates (subtypes A to J and circulating recombinant form AE) and group O isolates ranged from 0.1 to 4.5 nM (0.05 to 2.3 ng per mL) in cell culture. When used with other antiretroviral agents in cell culture, the combination of maraviroc was not antagonistic with NNRTIs (delavirdine, efavirenz, and nevirapine), NRTIs (abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, zalcitabine, and zidovudine), or protease inhibitors (amprenavir, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, and tipranavir). Maraviroc was not antagonistic with the HIV fusion inhibitor enfuvirtide. Maraviroc was not active against CXCR4-tropic and dual-tropic viruses (EC50 value greater than 10 µM). The antiviral activity of maraviroc against HIV-2 has not been evaluated. Maraviroc can cause serious, life-threatening side effects such as, liver problems, skin reactions, and allergic reactions.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
0.86 nM [Kd]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
SELZENTRY

Cmax

ValueDoseCo-administeredAnalytePopulation
538 ng/mL
300 mg 2 times / day steady-state, oral
MARAVIROC plasma
Homo sapiens
888 ng/mL
300 mg 2 times / day multiple, oral
MARAVIROC plasma
Homo sapiens
335.6 ng/mL
300 mg single, oral
MARAVIROC plasma
Homo sapiens
801.16 ng/mL
300 mg single, oral
MARAVIROC plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
2422 ng × h/mL
300 mg 2 times / day steady-state, oral
MARAVIROC plasma
Homo sapiens
2908 ng × h/mL
300 mg 2 times / day multiple, oral
MARAVIROC plasma
Homo sapiens
1320.7 ng*h/mL
300 mg single, oral
MARAVIROC plasma
Homo sapiens
4255.5 ng*h/mL
300 mg single, oral
MARAVIROC plasma
Homo sapiens
1348.4 ng*h/mL
300 mg single, oral
MARAVIROC plasma
Homo sapiens
4367.7 ng*h/mL
300 mg single, oral
MARAVIROC plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
8.63 h
300 mg 2 times / day steady-state, oral
MARAVIROC plasma
Homo sapiens
14.36 h
300 mg single, oral
MARAVIROC plasma
Homo sapiens
17.29 h
300 mg single, oral
MARAVIROC plasma
Homo sapiens

PubMed

Sample Use Guides

In Vivo Use Guide
The recommended dose of SELZENTRY (maraviroc tablets, for oral use) differs based on concomitant medications due to drug interactions. SELZENTRY can be taken with or without food. SELZENTRY must be given in combination with other antiretroviral medications.
Route of Administration: Oral
In Vitro Use Guide
PM-1 cells were infected with CCR5-tropic HIV-1 BaL in the presence or absence of inhibitory concentrations of maraviroc (MVC) 50 nM or controls. P24 and viral load levels were measured by ELISA and qRT-PCR after 4 hours.
Substance Class Chemical
Record UNII
MD6P741W8A
Record Status Validated (UNII)
Record Version