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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
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Celsentritablet150 mgoralViiv Healthcare Ulc2007-09-26Not applicableCanada
Celsentritablet300 mgoralViiv Healthcare Ulc2007-09-26Not applicableCanada
Selzentrytablet, film coated150 mg/1oralPfizer Laboratories Div Pfizer Inc2007-08-06Not applicableUs
Selzentrytablet, film coated300 mg/1oralPhysicians Total Care, Inc.2007-12-19Not applicableUs
Selzentrytablet, film coated150 mg/1oralREMEDYREPACK INC.2013-02-18Not applicableUs
Selzentrytablet, film coated300 mg/1oralVii V Healthcare Company2011-05-16Not applicableUs
Selzentrytablet, film coated150 mg/1oralVii V Healthcare Company2011-05-16Not applicableUs
Selzentrytablet, film coated300 mg/1oralPfizer Laboratories Div Pfizer Inc2007-08-06Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIMD6P741W8A
CAS number376348-65-1
WeightAverage: 513.6655
Monoisotopic: 513.327917369
Chemical FormulaC29H41F2N5O
InChI KeyGSNHKUDZZFZSJB-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-carboximidic acid
SMILES
[H][C@@](CCN1[C@@]2([H])CC[C@]1([H])C[C@]([H])(C2)N1C(C)=NN=C1C(C)C)(N=C(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 Descriptors
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.
Related Articles
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 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 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral150 mg
Tabletoral300 mg
Tablet, film coatedoral150 mg/1
Tablet, film coatedoral300 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)
CA2350073 No2007-04-172019-12-23Canada
CA2408909 No2006-06-272021-05-09Canada
US6586430 No1999-12-012019-12-01Us
US6667314 No2001-08-062021-08-06Us
US7368460 No2002-11-252022-11-25Us
US7576097 No2001-05-252021-05-25Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00883 mg/mLALOGPS
logP4.39ALOGPS
logP1.89ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)7.02ChemAxon
pKa (Strongest Basic)10.13ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area66.54 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity143.4 m3·mol-1ChemAxon
Polarizability56.84 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

DrugSyn.org

US020013337
General ReferencesNot Available
External Links
ATC CodesJ05AX09
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (241 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AprepitantThe serum concentration of Maraviroc can be increased when it is combined with Aprepitant.
AtazanavirThe serum concentration of Maraviroc can be increased when it is combined with Atazanavir.
BexaroteneThe serum concentration of Maraviroc can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of Maraviroc can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Maraviroc can be decreased when it is combined with Bosentan.
CarbamazepineThe serum concentration of Maraviroc can be decreased when it is combined with Carbamazepine.
CeritinibThe serum concentration of Maraviroc can be increased when it is combined with Ceritinib.
ClarithromycinThe serum concentration of Maraviroc can be increased when it is combined with Clarithromycin.
CobicistatThe serum concentration of Maraviroc can be increased when it is combined with Cobicistat.
ConivaptanThe serum concentration of Maraviroc can be increased when it is combined with Conivaptan.
DabrafenibThe serum concentration of Maraviroc can be decreased when it is combined with Dabrafenib.
DarunavirThe serum concentration of Maraviroc can be increased when it is combined with Darunavir.
DasatinibThe serum concentration of Maraviroc can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Maraviroc can be decreased when it is combined with Deferasirox.
EfavirenzThe serum concentration of Maraviroc can be decreased when it is combined with Efavirenz.
EnzalutamideThe serum concentration of Maraviroc can be decreased when it is combined with Enzalutamide.
EtravirineThe serum concentration of Maraviroc can be decreased when it is combined with Etravirine.
FluconazoleThe metabolism of Maraviroc can be decreased when combined with Fluconazole.
FosaprepitantThe serum concentration of Maraviroc can be increased when it is combined with Fosaprepitant.
FosphenytoinThe serum concentration of Maraviroc can be decreased when it is combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Maraviroc can be increased when it is combined with Fusidic Acid.
IdelalisibThe serum concentration of Maraviroc can be increased when it is combined with Idelalisib.
IndinavirThe serum concentration of Maraviroc can be increased when it is combined with Indinavir.
ItraconazoleThe serum concentration of Maraviroc can be increased when it is combined with Itraconazole.
IvacaftorThe serum concentration of Maraviroc can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Maraviroc can be increased when it is combined with Ketoconazole.
LuliconazoleThe serum concentration of Maraviroc can be increased when it is combined with Luliconazole.
MifepristoneThe serum concentration of Maraviroc can be increased when it is combined with Mifepristone.
MitotaneThe serum concentration of Maraviroc can be decreased when it is combined with Mitotane.
NefazodoneThe serum concentration of Maraviroc can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Maraviroc can be increased when it is combined with Nelfinavir.
NetupitantThe serum concentration of Maraviroc can be increased when it is combined with Netupitant.
PalbociclibThe serum concentration of Maraviroc can be increased when it is combined with Palbociclib.
PhenobarbitalThe serum concentration of Maraviroc can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Maraviroc can be decreased when it is combined with Phenytoin.
PosaconazoleThe serum concentration of Maraviroc can be increased when it is combined with Posaconazole.
PrimidoneThe serum concentration of Maraviroc can be decreased when it is combined with Primidone.
RifabutinThe serum concentration of Maraviroc can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Maraviroc can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Maraviroc can be decreased when it is combined with Rifapentine.
RitonavirThe serum concentration of Maraviroc can be increased when it is combined with Ritonavir.
SaquinavirThe serum concentration of Maraviroc can be increased when it is combined with Saquinavir.
SiltuximabThe serum concentration of Maraviroc can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Maraviroc can be increased when it is combined with Simeprevir.
St. John's WortThe serum concentration of Maraviroc can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Maraviroc can be increased when it is combined with Stiripentol.
TelaprevirThe serum concentration of Maraviroc can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Maraviroc can be increased when it is combined with Telithromycin.
TocilizumabThe serum concentration of Maraviroc can be decreased when it is combined with Tocilizumab.
VoriconazoleThe serum concentration of Maraviroc can be increased when it is combined with Voriconazole.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
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 role in the control of granulocytic lineage proliferation or differentiation. Acts as a coreceptor (CD4 being the primary receptor) for HIV-1 R5 isolates.(Microbial infection) Acts as a receptor for hu...
Gene Name:
CCR5
Uniprot ID:
P51681
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. [PubMed:17139284 ]
  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:17016423 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  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. [PubMed:19098484 ]
  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. [PubMed:19692476 ]
  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:16298345 ]

Enzymes

Kind
Protein
Organism
Human
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
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. [PubMed:19704163 ]
  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. [PubMed:18333864 ]
  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. [PubMed:21080015 ]
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Drug created on September 11, 2007 19:14 / Updated on August 24, 2016 01:51