U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C29H41F2N5O
Molecular Weight 513.6666
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MARAVIROC

SMILES

CC(C)c1nnc(C)n1[C@@]2([H])C[C@]3([H])CC[C@]([H])(C2)N3CC[C@@]([H])(c4ccccc4)N=C(C5CCC(CC5)(F)F)O

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 513.6666
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16251317

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

Curator's Comment:: Several factors suggest maraviroc may have CNS antiviral activity. First, due to pharmacological properties, such as a relatively low degree of plasma protein binding (∼76%), maraviroc may theoretically cross the blood–brain barrier (BBB) and gain exposure in the CSF at concentrations great enough to suppress HIV viral replication. Second, as a predominance of CCR5-tropic HIV has been described within the CNS, CCR5 inhibitors such as maraviroc may have profound antiviral activity within this compartment.

Originator

Curator's Comment:: from a high-throughput screen of the Pfizer compound file # Pfizer

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.86 nM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
SELZENTRY

Approved Use

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 studies of SELZENTRY in treatment-experienced subjects and one study in treatment-naïve subjects. Both studies in treatment-experienced subjects were conducted in clinically advanced, 3-class antiretroviral-experienced (NRTI, NNRTI, PI, or enfuvirtide) adults with evidence of HIV-1 replication despite ongoing antiretroviral therapy. The following points should be considered when initiating therapy with SELZENTRY: Adult patients infected with only CCR5-tropic HIV-1 should use SELZENTRY. Tropism testing must be conducted with a highly sensitive tropism assay that has demonstrated the ability to identify patients appropriate for SELZENTRY use. Outgrowth of pre-existing low-level CXCR4- or dual/mixed-tropic HIV-1 not detected by tropism testing at screening has been associated with virologic failure on SELZENTRY. [see Microbiology (12.4) Clinical Studies (14.3)

Launch Date

1.18635836E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
538 ng/mL
300 mg 2 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
MARAVIROC plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
888 ng/mL
300 mg 2 times / day multiple, oral
dose: 300 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MARAVIROC plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
335.6 ng/mL
300 mg single, oral
dose: 300 mg
route of administration: oral
experiment type: single
co-administered:
MARAVIROC plasma
Homo sapiens
population: healthy
age:
sex:
food status:
801.16 ng/mL
300 mg single, oral
dose: 300 mg
route of administration: oral
experiment type: single
co-administered:
MARAVIROC plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2422 ng × h/mL
300 mg 2 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
MARAVIROC plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2908 ng × h/mL
300 mg 2 times / day multiple, oral
dose: 300 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MARAVIROC plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
1320.7 ng*h/mL
300 mg single, oral
dose: 300 mg
route of administration: oral
experiment type: single
co-administered:
MARAVIROC plasma
Homo sapiens
population: healthy
age:
sex:
food status:
4255.5 ng*h/mL
300 mg single, oral
dose: 300 mg
route of administration: oral
experiment type: single
co-administered:
MARAVIROC plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
1348.4 ng*h/mL
300 mg single, oral
dose: 300 mg
route of administration: oral
experiment type: single
co-administered:
MARAVIROC plasma
Homo sapiens
population: healthy
age:
sex:
food status:
4367.7 ng*h/mL
300 mg single, oral
dose: 300 mg
route of administration: oral
experiment type: single
co-administered:
MARAVIROC plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.63 h
300 mg 2 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
MARAVIROC plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
14.36 h
300 mg single, oral
dose: 300 mg
route of administration: oral
experiment type: single
co-administered:
MARAVIROC plasma
Homo sapiens
population: healthy
age:
sex:
food status:
17.29 h
300 mg single, oral
dose: 300 mg
route of administration: oral
experiment type: single
co-administered:
MARAVIROC plasma
Homo sapiens
population: unhealthy
age:
sex:
food status:
PubMed

PubMed

TitleDatePubMed
Maraviroc.
2007
V3 loop truncations in HIV-1 envelope impart resistance to coreceptor inhibitors and enhanced sensitivity to neutralizing antibodies.
2007 Aug 24
Maraviroc (Celsentri) for multidrug-resistant human immunodeficiency virus (HIV)-1.
2007 Dec
Allosteric modulation of heterodimeric G-protein-coupled receptors.
2007 Dec
Asymmetric allylboration of acyl imines catalyzed by chiral diols.
2007 Dec 12
Species selectivity of small-molecular antagonists for the CCR5 chemokine receptor.
2007 Dec 5
Host factors influencing susceptibility to HIV infection and AIDS progression.
2007 Jul 25
Maraviroc--new HIV drug. Emerging options need to be used wisely.
2007 Jul-Aug
Translational research: application to HIV/AIDS.
2007 Jun
FDA panel backs HIV drug.
2007 Jun
Anti-HIV agents. Access to maraviroc.
2007 Mar-Apr
Anti-HIV agents. Maraviroc--absorption and drug-interaction issues.
2007 Mar-Apr
Anti-HIV agents. Getting to know your co-receptors.
2007 Mar-Apr
Maraviroc.
2007 Nov
Randomized trials to optimize treatment of multidrug-resistant tuberculosis.
2007 Nov 6
New drugs: Maraviroc and Lanreotide.
2007 Nov-Dec
Antiviral drugs in the treatment of AIDS: what is in the pipeline ?
2007 Oct 15
Treatment with CCR5 antagonists: which patient may have a benefit?
2007 Oct 15
How will CCR5 antagonists influence the recommendations for the antiretroviral treatment of HIV-1 infection.
2007 Oct 15
CCR5 antagonists in the treatment of treatment-naive patients infected with CCR5 tropic HIV-1.
2007 Oct 15
CCR5 antagonists in the treatment of treatment-experienced patients infected with CCR5 tropic HIV-1.
2007 Oct 15
CCR5 antagonists: comparison of efficacy, side effects, pharmacokinetics and interactions--review of the literature.
2007 Oct 15
Changes in HIV-1 tropism: clinical and prognostic consequences.
2007 Oct 15
FDA approves maraviroc tablets.
2007 Sep
FDA approves drug for resistant HIV.
2007 Sep
Phylodynamics of HIV-1 in lymphoid and non-lymphoid tissues reveals a central role for the thymus in emergence of CXCR4-using quasispecies.
2007 Sep 26
Anti-HIV agents. New drugs--hope and a degree of caution.
2007 Sep-Oct
Anti-HIV agents. Using maraviroc in first-line therapy.
2007 Sep-Oct
Anti-HIV agents. Maraviroc and resistance.
2007 Sep-Oct
Anti-HIV agents. One year clinical trial results with maraviroc.
2007 Sep-Oct
Anti-HIV agents. Maraviroc approved in Canada.
2007 Sep-Oct
A receptor theory-based semimechanistic PD model for the CCR5 noncompetitive antagonist maraviroc.
2008 Apr
Population pharmacokinetic/pharmacodynamic analysis of CCR5 receptor occupancy by maraviroc in healthy subjects and HIV-positive patients.
2008 Apr
A population pharmacokinetic meta-analysis of maraviroc in healthy volunteers and asymptomatic HIV-infected subjects.
2008 Apr
Effect of single doses of maraviroc on the QT/QTc interval in healthy subjects.
2008 Apr
Assessment of the absorption, metabolism and absolute bioavailability of maraviroc in healthy male subjects.
2008 Apr
A novel probe drug interaction study to investigate the effect of selected antiretroviral combinations on the pharmacokinetics of a single oral dose of maraviroc in HIV-positive subjects.
2008 Apr
The effects of cotrimoxazole or tenofovir co-administration on the pharmacokinetics of maraviroc in healthy volunteers.
2008 Apr
Effects of CYP3A4 inducers with and without CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers.
2008 Apr
Effects of CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers.
2008 Apr
Effect of maraviroc on the pharmacokinetics of midazolam, lamivudine/zidovudine, and ethinyloestradiol/levonorgestrel in healthy volunteers.
2008 Apr
Assessment of the pharmacokinetics, safety and tolerability of maraviroc, a novel CCR5 antagonist, in healthy volunteers.
2008 Apr
A review of the clinical pharmacology of maraviroc. Introduction.
2008 Apr
The incidence of multidrug and full class resistance in HIV-1 infected patients is decreasing over time (2001-2006) in Portugal.
2008 Feb 1
Anti-HIV-1 entry optimization of novel imidazopiperidine-tropane CCR5 antagonists.
2008 Feb 15
Post-exposure prophylaxis with a maraviroc-containing regimen after occupational exposure to a multi-resistant HIV-infected source person.
2008 Jan
Two new drugs for HIV infection.
2008 Jan 14
Variation in HIV-1 R5 macrophage-tropism correlates with sensitivity to reagents that block envelope: CD4 interactions but not with sensitivity to other entry inhibitors.
2008 Jan 18
CXCR2 chemokine receptor antagonism enhances DOP opioid receptor function via allosteric regulation of the CXCR2-DOP receptor heterodimer.
2008 Jun 1
Molecular interactions of CCR5 with major classes of small-molecule anti-HIV CCR5 antagonists.
2008 Mar
Patents

Sample Use Guides

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
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
Created
by admin
on Sat Jun 26 12:28:53 UTC 2021
Edited
by admin
on Sat Jun 26 12:28:53 UTC 2021
Record UNII
MD6P741W8A
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MARAVIROC
EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   VANDF   WHO-DD  
INN  
Official Name English
4,4-DIFLUORO-N-((1S)-3-((1R,3S,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)CYCLOHEXANECARBOXAMIDE
Common Name English
MARAVIROC [INN]
Common Name English
MARAVIROC [EMA EPAR]
Common Name English
MARAVIROC [VANDF]
Common Name English
MARAVIROC [MART.]
Common Name English
MARAVIROC [JAN]
Common Name English
MARAVIROC [WHO-DD]
Common Name English
CELSENTRI
Brand Name English
SELZENTRY
Brand Name English
MARAVIROC [MI]
Common Name English
MARAVIROC [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
LIVERTOX 582
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
NDF-RT N0000175572
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
WHO-VATC QJ05AX09
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
NCI_THESAURUS C1660
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
NCI_THESAURUS C63817
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
EMA ASSESSMENT REPORTS CELSENTRI (AUTHORIZED: HIV INFECTIONS)
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
WHO-ATC J05AX09
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
NDF-RT N0000175445
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
Code System Code Type Description
MESH
C502411
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
PRIMARY
HSDB
8021
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
PRIMARY
EPA CompTox
376348-65-1
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
PRIMARY
DRUG CENTRAL
1635
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
PRIMARY
IUPHAR
806
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
PRIMARY
INN
8450
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
PRIMARY
EVMPD
SUB25224
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
PRIMARY
CAS
376348-65-1
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
PRIMARY
NCI_THESAURUS
C73144
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
PRIMARY
FDA UNII
MD6P741W8A
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
PRIMARY
MERCK INDEX
M7084
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
PRIMARY Merck Index
ChEMBL
CHEMBL1201187
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
PRIMARY
RXCUI
620216
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
PRIMARY RxNorm
WIKIPEDIA
MARAVIROC
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
PRIMARY
LACTMED
Maraviroc
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
PRIMARY
DRUG BANK
DB04835
Created by admin on Sat Jun 26 12:28:53 UTC 2021 , Edited by admin on Sat Jun 26 12:28:53 UTC 2021
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
METABOLIC ENZYME -> SUBSTRATE
TARGET ORGANISM->INHIBITOR
TRANSPORTER -> SUBSTRATE
TARGET->ANTAGONIST
BINDER->LIGAND
BINDING
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
<1% radioactivity
MINOR
FECAL; PLASMA; URINE
METABOLITE -> PARENT
METABOLITE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

SINGLE AND MULTIPLE DOSE

blood-to-plasma ratio PHARMACOKINETIC