Maraviroc

Identification

Summary

Maraviroc is a CCR5 co-receptor antagonist used with other antiretroviral medications to treat CCR5-tropic HIV-1 infection.

Brand Names
Celsentri, Selzentry
Generic Name
Maraviroc
DrugBank Accession Number
DB04835
Background

Maraviroc (brand-named Selzentry, or Celsentri outside the U.S.) is a chemokine receptor antagonist drug developed by the drug company Pfizer that is designed to act against HIV by interfering with the interaction between HIV and CCR5. It was originally labelled as UK-427857 during development but was assigned the Maraviroc name as it entered trials. It was approved for use by the FDA in August, 2007.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 513.6655
Monoisotopic: 513.327917369
Chemical Formula
C29H41F2N5O
Synonyms
  • Maraviroc
  • Maravirocum

Pharmacology

Indication

Maraviroc is indicated in combination with other antiretroviral agents for the treatment of CCR5-tropic HIV-1 infection in adults and pediatric patients weighing at least 2kg.1 It is not recommended in patients with dual/mixed- or CXCR4-tropic HIV-1.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Adjunct therapy in treatment ofCcr5-tropic human immunodeficiency virus type 1 (hiv-1) infection••••••••••••••••••••••••••• ••••••••••••• ••••••
Adjunct therapy in treatment ofCcr5-tropic human immunodeficiency virus type 1 (hiv-1) infection•••••••••••••••••••••••••• ••••••
Used in combination to treatHiv-1 infection••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Maraviroc is a chemokine receptor antagonist drug developed by the drug company Pfizer that is designed to act against HIV by interfering with the interaction between HIV and CCR5.

Mechanism of action

Maraviroc is an entry inhibitor and works by blocking HIV from entering human cells. Specifically maraviroc is a selective, slowly reversible, small molecule antagonist of the interaction between human CCR5 and HIV-1 gp120. Maraviroc selectively binds to the human chemokine receptor CCR5 present on the membrane of CD4 cells (T-cells), preventing the interaction of HIV-1 gp120 and CCR5 necessary for CCR5-tropic HIV-1 to enter cells.

TargetActionsOrganism
AC-C chemokine receptor type 5
antagonist
inhibitor
Humans
Absorption

The absolute oral bioavailability of a 100 mg dose is 23% and is predicted to be 33% at 300 mg. Coadministration of a 300mg tablet with a high fat breakfast reduced maraviroc Cmax and AUC by 33% in healthy volunteers.

Volume of distribution
  • 194 L
Protein binding

Approximately 76% bound to human plasma proteins, with moderate affinity for albumin and alpha-1 acid glycoprotein.

Metabolism

In vitro studies indicate that CYP3A is the major enzyme responsible for maraviroc metabolism.

Route of elimination

Not Available

Half-life

14-18 hours

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Maraviroc can be increased when it is combined with Abametapir.
AdagrasibThe serum concentration of Maraviroc can be increased when it is combined with Adagrasib.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Maraviroc.
AmiodaroneThe metabolism of Maraviroc can be decreased when combined with Amiodarone.
AmprenavirThe metabolism of Maraviroc can be decreased when combined with Amprenavir.
Food Interactions
  • Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of maraviroc.
  • Take with or without food.

Products

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Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CelsentriTablet, film coated300 mgOralVii V Healthcare B.V.2016-09-08Not applicableEU flag
CelsentriTablet, film coated150 mgOralVii V Healthcare B.V.2016-09-08Not applicableEU flag
CelsentriTablet, film coated150 mgOralVii V Healthcare B.V.2016-09-08Not applicableEU flag
CelsentriTablet150 mgOralViiV Healthcare ULC2007-09-26Not applicableCanada flag
CelsentriTablet, film coated75 mgOralVii V Healthcare B.V.2020-12-16Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
MaravirocTablet, film coated300 mg/1OralXLCARE Pharmaceuticals INC.2023-06-01Not applicableUS flag
MaravirocTablet, film coated150 mg/1OralCamber Pharmaceuticals, Inc.2022-02-06Not applicableUS flag
MaravirocTablet, film coated300 mg/1Orali3 Pharmaceuticals, LLC2023-09-15Not applicableUS flag
MaravirocTablet, film coated150 mg/1OralXLCARE Pharmaceuticals INC.2023-06-01Not applicableUS flag
MaravirocTablet, film coated150 mg/1Orali3 Pharmaceuticals, LLC2023-09-15Not applicableUS flag

Categories

ATC Codes
J05AX09 — Maraviroc
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as tropane alkaloids. These are organic compounds containing the nitrogenous bicyclic alkaloid parent N-Methyl-8-azabicyclo[3.2.1]octane.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Tropane alkaloids
Sub Class
Not Available
Direct Parent
Tropane alkaloids
Alternative Parents
Aralkylamines / Cyclohexyl halides / Piperidines / N-alkylpyrrolidines / Benzene and substituted derivatives / Triazoles / Heteroaromatic compounds / Trialkylamines / Secondary carboxylic acid amides / Amino acids and derivatives
show 7 more
Substituents
1,2,4-triazole / Alkyl fluoride / Alkyl halide / Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, azabicycloalkane, monocarboxylic acid amide, triazoles (CHEBI:63608)
Affected organisms
  • Human Immunodeficiency Virus

Chemical Identifiers

UNII
MD6P741W8A
CAS number
376348-65-1
InChI Key
GSNHKUDZZFZSJB-QYOOZWMWSA-N
InChI
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
IUPAC Name
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]cyclohexane-1-carboxamide
SMILES
CC(C)C1=NN=C(C)N1[C@H]1C[C@@H]2CC[C@H](C1)N2CC[C@H](NC(=O)C1CCC(F)(F)CC1)C1=CC=CC=C1

References

Synthesis Reference
US020013337
General References
  1. FDA Approved Drug Products: Selzentry (maraviroc) for oral use [Link]
PubChem Compound
3002977
PubChem Substance
46508040
ChemSpider
20078004
BindingDB
50334986
RxNav
620216
ChEBI
63608
ChEMBL
CHEMBL1201187
ZINC
ZINC000100003902
Therapeutic Targets Database
DNC001487
PharmGKB
PA164768835
Guide to Pharmacology
GtP Drug Page
PDBe Ligand
MRV
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Maraviroc
PDB Entries
4mbs

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Goedecke GmbH
  • Lake Erie Medical and Surgical Supply
  • Pfizer Inc.
  • Physicians Total Care Inc.
  • ViiV Healthcare ULC
Dosage Forms
FormRouteStrength
SolutionOral20 MG/ML
TabletOral150 mg
TabletOral300 mg
Tablet, film coatedOral25 MG
Tablet, film coatedOral75 MG
Tablet, coatedOral150 mg
Tablet, coatedOral300 mg
Tablet, coatedOral
Tablet, film coatedOral150 mg
Tablet, film coatedOral300 mg
Kit; solutionOral20 mg/1mL
SolutionOral20 mg/1mL
TabletOral150.000 mg
Tablet, film coatedOral150 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral300 mg/1
Tablet, film coatedOral75 mg/1
Prices
Unit descriptionCostUnit
Selzentry 150 mg tablet18.36USD tablet
Selzentry 300 mg tablet18.36USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2350073No2007-04-172019-12-23Canada flag
CA2408909No2006-06-272021-05-09Canada flag
US6586430No2003-07-012019-12-01US flag
US6667314Yes2003-12-232022-02-06US flag
US7368460Yes2008-05-062023-05-25US flag
US7576097Yes2009-08-182021-11-25US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0106 mg/mLALOGPS
logP4.3ALOGPS
logP3.63Chemaxon
logS-4.7ALOGPS
pKa (Strongest Acidic)13.98Chemaxon
pKa (Strongest Basic)9.65Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area63.05 Å2Chemaxon
Rotatable Bond Count8Chemaxon
Refractivity142.88 m3·mol-1Chemaxon
Polarizability56.02 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.997
Blood Brain Barrier+0.8329
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.6716
P-glycoprotein inhibitor IInhibitor0.8931
P-glycoprotein inhibitor IIInhibitor0.9431
Renal organic cation transporterNon-inhibitor0.5695
CYP450 2C9 substrateNon-substrate0.8308
CYP450 2D6 substrateNon-substrate0.7344
CYP450 3A4 substrateSubstrate0.8199
CYP450 1A2 substrateNon-inhibitor0.8616
CYP450 2C9 inhibitorInhibitor0.6028
CYP450 2D6 inhibitorNon-inhibitor0.8331
CYP450 2C19 inhibitorInhibitor0.5684
CYP450 3A4 inhibitorInhibitor0.6066
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7814
Ames testNon AMES toxic0.63
CarcinogenicityNon-carcinogens0.706
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7115 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9864
hERG inhibition (predictor II)Inhibitor0.8971
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0000290000-936866526b59a59af560
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-0700390000-a4f3a05567a4e43fd442
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0045590000-65ffe5f4de44e0680f31
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03ec-2600950000-8c10575728b3d2684429
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-01r2-0932210000-79918d7ffc0a8bbb44a9
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-03dl-4620920000-21d3f106baadb797b6e6
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-219.8899
predicted
DeepCCS 1.0 (2019)
[M+H]+221.7853
predicted
DeepCCS 1.0 (2019)
[M+Na]+227.6039
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
Inhibitor
General Function
Virus receptor activity
Specific Function
Receptor for a number of inflammatory CC-chemokines including MIP-1-alpha, MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May play a r...
Gene Name
CCR5
Uniprot ID
P51681
Uniprot Name
C-C chemokine receptor type 5
Molecular Weight
40523.645 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  4. Levy JA: HIV pathogenesis: 25 years of progress and persistent challenges. AIDS. 2009 Jan 14;23(2):147-60. doi: 10.1097/QAD.0b013e3283217f9f. [Article]
  5. Agrawal-Gamse C, Lee FH, Haggarty B, Jordan AP, Yi Y, Lee B, Collman RG, Hoxie JA, Doms RW, Laakso MM: Adaptive mutations in a human immunodeficiency virus type 1 envelope protein with a truncated V3 loop restore function by improving interactions with CD4. J Virol. 2009 Nov;83(21):11005-15. doi: 10.1128/JVI.01238-09. Epub 2009 Aug 19. [Article]
  6. Napier C, Sale H, Mosley M, Rickett G, Dorr P, Mansfield R, Holbrook M: Molecular cloning and radioligand binding characterization of the chemokine receptor CCR5 from rhesus macaque and human. Biochem Pharmacol. 2005 Dec 19;71(1-2):163-72. Epub 2005 Nov 18. [Article]
  7. Clark IA, Vissel B: Neurodegenerative disease treatments by direct TNF reduction, SB623 cells, maraviroc and irisin and MCC950, from an inflammatory perspective - a Commentary. Expert Rev Neurother. 2019 Jun;19(6):535-543. doi: 10.1080/14737175.2019.1618710. Epub 2019 May 24. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Abel S, Back DJ, Vourvahis M: Maraviroc: pharmacokinetics and drug interactions. Antivir Ther. 2009;14(5):607-18. [Article]
  2. Abel S, Jenkins TM, Whitlock LA, Ridgway CE, Muirhead GJ: Effects of CYP3A4 inducers with and without CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers. Br J Clin Pharmacol. 2008 Apr;65 Suppl 1:38-46. doi: 10.1111/j.1365-2125.2008.03134.x. [Article]
  3. Mannu J, Jenardhanan P, Mathur PP: A computational study of CYP3A4 mediated drug interaction profiles for anti-HIV drugs. J Mol Model. 2011 Aug;17(8):1847-54. doi: 10.1007/s00894-010-0890-6. Epub 2010 Nov 16. [Article]

Drug created at September 12, 2007 01:14 / Updated at March 18, 2024 16:48