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Maraviroc

July 24, 2017
Common Name

Maraviroc 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

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source SelzentryMeSH Pfizer brand OF maravirocMeSH 4,4-difluoro-N-((1S)-3-(exo-3-(3-Isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo(3.2.1)oct-8-yl)-1-phenylpropyl)cyclohexanecarboxamideMeSH

Chemical Formlia

C29H41F2N5O Average Molecliar Weight

513.6655 Monoisotopic Molecliar Weight

513.327917369 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 Traditional Name

selzentry CAS Registry Number

376348-65-1 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

InChI Identifier

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

InChI Key

GSNHKUDZZFZSJB-HLMSNRGBSA-N Chemical Taxonomy Classification

Not classified Ontology Status

Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anti-HIV Agents

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility1.06e-02 g/LNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source Water Solubility0.011 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 Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Not Available Biological Properties Cellliar Locations

  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB04835

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB04835

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB04835 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    2273675 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Maraviroc NuGOwiki Link

    HMDB15584 Metagene Link

    HMDB15584 METLIN ID

    Not Available PubChem Compound

    3002977 PDB ID

    Not Available ChEBI ID

    Not Available

    Product: Galanthaminone

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References Not Available

    Enzymes

    General function:
    Involved in monooxygenase 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 xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
    Gene Name:
    CYP3A4
    Uniprot ID:
    P08684
    Molecular weight:
    57255.585
    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 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    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
    Gene Name:
    CCR5
    Uniprot ID:
    P51681
    Molecular weight:
    40523.6
    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 ]

    PMID: 21355588

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