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Identification
NameMaraviroc
Accession NumberDB04835
TypeSmall Molecule
GroupsApproved, Investigational
Description

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.

Structure
Thumb
SynonymsNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Selzentrytablet, film coated150 mgoralPfizer Laboratories Div Pfizer Inc2007-08-06Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Selzentrytablet, film coated300 mgoralPfizer Laboratories Div Pfizer Inc2007-08-06Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Selzentrytablet, film coated300 mgoralVii V Healthcare Company2010-09-012015-03-31Us 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Selzentrytablet, film coated150 mgoralVii V Healthcare Company2011-05-16Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Selzentrytablet, film coated300 mgoralVii V Healthcare Company2011-05-16Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Selzentrytablet, film coated150 mgoralREMEDYREPACK INC.2013-02-18Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Selzentrytablet, film coated300 mgoralPhysicians Total Care, Inc.2007-12-19Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Celsentritablet150 mgoralViiv Healthcare UlcNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Celsentritablet300 mgoralViiv Healthcare UlcNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
CAS number376348-65-1
WeightAverage: 513.6655
Monoisotopic: 513.327917369
Chemical FormulaC29H41F2N5O
InChI KeyGSNHKUDZZFZSJB-HLMSNRGBSA-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,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
[H][C@]12CC[C@]([H])(CC(C1)N1C(C)=NN=C1C(C)C)N2CC[C@H](NC(=O)C1CCC(F)(F)CC1)C1=CC=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylpropylamines. These are compounds containing a phenylpropylamine moiety, which consists of a phenyl group substituted at the third carbon by an propan-1-amine.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylpropylamines
Direct ParentPhenylpropylamines
Alternative Parents
Substituents
  • Phenylpropylamine
  • Tropane alkaloid
  • Aralkylamine
  • 4-aminopiperidine
  • N-alkylpyrrolidine
  • Piperidine
  • Heteroaromatic compound
  • 1,2,4-triazole
  • Pyrrolidine
  • Azole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Alkyl halide
  • Alkyl fluoride
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor treatment-experienced adult patients infected with only CCR5-tropic HIV-1 detectable, who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.
PharmacodynamicsMaraviroc 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 actionMaraviroc 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.
AbsorptionThe 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 bindingApproximately 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 eliminationNot Available
Half life14-18 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Human Immunodeficiency Virus
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrateInhibitor0.6028
CYP450 2D6 substrateNon-inhibitor0.8331
CYP450 2C19 substrateInhibitor0.5684
CYP450 3A4 substrateInhibitor0.6066
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
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral150 mg
Tabletoral300 mg
Tablet, film coatedoral150 mg
Tablet, film coatedoral300 mg
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
CountryPatent NumberApprovedExpires (estimated)
Canada23500732007-04-172019-12-23
Canada24089092006-06-272021-05-09
United States65864301999-12-012019-12-01
United States73684602002-11-252022-11-25
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0106 mg/mLALOGPS
logP4.3ALOGPS
logP3.63ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)14.5ChemAxon
pKa (Strongest Basic)9.38ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area63.05 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity142.88 m3·mol-1ChemAxon
Polarizability55.59 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US020013337
General ReferenceNot Available
External Links
ATC CodesJ05AX09
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (241 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AprepitantMay increase the serum concentration of CYP3A4 Substrates.
AtazanavirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
BoceprevirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
BosentanMay decrease the serum concentration of CYP3A4 Substrates.
CarbamazepineCYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc.
ClarithromycinCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
ConivaptanMay increase the serum concentration of CYP3A4 Substrates.
DabrafenibMay decrease the serum concentration of CYP3A4 Substrates.
DarunavirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
DasatinibMay increase the serum concentration of CYP3A4 Substrates.
DeferasiroxMay decrease the serum concentration of CYP3A4 Substrates.
DelavirdineCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
EfavirenzMay decrease the serum concentration of Maraviroc. Of note, this effect only applies in the absence of a strong CYP3A4 inhibitor
EnzalutamideCYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc.
EtravirineMay decrease the serum concentration of Maraviroc. Of note, this effect only applies in the absence of a strong CYP3A4 inhibitor
FosamprenavirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
FosaprepitantMay increase the serum concentration of CYP3A4 Substrates.
FosphenytoinCYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc.
IndinavirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
ItraconazoleCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
IvacaftorMay increase the serum concentration of CYP3A4 Substrates.
LopinavirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
LULICONAZOLEMay increase the serum concentration of CYP3A4 Substrates.
MifepristoneMay increase the serum concentration of CYP3A4 Substrates.
MitotaneMay decrease the serum concentration of CYP3A4 Substrates.
NefazodoneCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
NelfinavirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
PhenobarbitalCYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc.
PhenytoinCYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc.
PosaconazoleCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
PrimidoneCYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc.
RifampicinCYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc.
RifapentineCYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc.
RitonavirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
SaquinavirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
SiltuximabMay decrease the serum concentration of CYP3A4 Substrates.
SimeprevirMay increase the serum concentration of CYP3A4 Substrates.
TelaprevirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
TelithromycinCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
TocilizumabMay decrease the serum concentration of CYP3A4 Substrates.
VoriconazoleCYP3A4 Inhibitors (Strong) may increase the serum concentration of Maraviroc.
Food InteractionsNot Available

Targets

1. C-C chemokine receptor type 5

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
C-C chemokine receptor type 5 P51681 Details

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. Pubmed
  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. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  4. Levy JA: HIV pathogenesis: 25 years of progress and persistent challenges. AIDS. 2009 Jan 14;23(2):147-60. Pubmed
  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. Epub 2009 Aug 19. Pubmed
  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. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Abel S, Back DJ, Vourvahis M: Maraviroc: pharmacokinetics and drug interactions. Antivir Ther. 2009;14(5):607-18. Pubmed
  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. Pubmed
  3. Mannu J, Jenardhanan P, Mathur PP: A computational study of CYP3A4 mediated drug interaction profiles for anti-HIV drugs. J Mol Model. 2010 Nov 16. Pubmed

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Drug created on September 11, 2007 19:14 / Updated on October 08, 2013 14:24