Identification

Name
Maraviroc
Accession Number
DB04835
Type
Small Molecule
Groups
Approved, 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
Synonyms
Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CelsentriTablet, film coated150 mgOralViiV Healthcare ULC2007-09-18Not applicableEu
CelsentriTablet150 mgOralViiV Healthcare ULC2007-09-26Not applicableCanada
CelsentriTablet, film coated300 mgOralViiV Healthcare ULC2007-09-18Not applicableEu
CelsentriTablet, film coated300 mgOralViiV Healthcare ULC2007-09-18Not applicableEu
CelsentriTablet, film coated150 mgOralViiV Healthcare ULC2007-09-18Not applicableEu
CelsentriTablet, film coated150 mgOralViiV Healthcare ULC2007-09-18Not applicableEu
CelsentriTablet, film coated300 mgOralViiV Healthcare ULC2007-09-18Not applicableEu
CelsentriTablet, film coated300 mgOralViiV Healthcare ULC2007-09-18Not applicableEu
CelsentriTablet, film coated150 mgOralViiV Healthcare ULC2007-09-18Not applicableEu
CelsentriTablet300 mgOralViiV Healthcare ULC2007-09-26Not applicableCanada
Categories
UNII
MD6P741W8A
CAS number
376348-65-1
Weight
Average: 513.6655
Monoisotopic: 513.327917369
Chemical Formula
C29H41F2N5O
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-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

Pharmacology

Indication

For 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.

Associated Conditions
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
Human
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
Toxicity
Not Available
Affected organisms
  • Human Immunodeficiency Virus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Maraviroc can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Maraviroc can be decreased when combined with (S)-Warfarin.
3,5-diiodothyropropionic acidThe metabolism of Maraviroc can be decreased when combined with 3,5-diiodothyropropionic acid.
4-hydroxycoumarinThe metabolism of Maraviroc can be decreased when combined with 4-hydroxycoumarin.
5-androstenedioneThe metabolism of Maraviroc can be decreased when combined with 5-androstenedione.
6-O-benzylguanineThe metabolism of Maraviroc can be decreased when combined with 6-O-benzylguanine.
AbemaciclibThe metabolism of Maraviroc can be decreased when combined with Abemaciclib.
AbirateroneThe metabolism of Maraviroc can be decreased when combined with Abiraterone.
AcenocoumarolThe metabolism of Maraviroc can be decreased when combined with Acenocoumarol.
AdinazolamThe metabolism of Maraviroc can be decreased when combined with Adinazolam.
Food Interactions
Not Available

References

Synthesis Reference
US020013337
General References
Not Available
External Links
PubChem Compound
3002977
PubChem Substance
46508040
ChemSpider
20078004
BindingDB
50334986
ChEBI
63608
ChEMBL
CHEMBL1201187
Therapeutic Targets Database
DNC001487
PharmGKB
PA164768835
IUPHAR
806
Guide to Pharmacology
GtP Drug Page
HET
MRV
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Maraviroc
ATC Codes
J05AX09 — Maraviroc
AHFS Codes
  • 08:18.08.04 — HIV Fusion Inhibitors
PDB Entries
4mbs
FDA label
Download (241 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0TerminatedTreatmentInfection, Human Immunodeficiency Virus I1
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV)1
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections / Infection, Human Immunodeficiency Virus I / Mycobacterium avium complex infection1
1CompletedNot AvailableInfection, Human Immunodeficiency Virus I1
1CompletedBasic ScienceCytochrome P450 CYP3A5 Enzyme Polymorphism / Healthy Volunteers / Pharmacokinetics of Maraviroc1
1CompletedBasic ScienceHealthy Volunteers2
1CompletedBasic ScienceHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
1CompletedHealth Services ResearchHuman Immunodeficiency Virus (HIV)1
1CompletedPreventionHealthy Adult Females1
1CompletedPreventionHuman Immunodeficiency Virus (HIV)1
1CompletedTreatmentHealthy Volunteers3
1CompletedTreatmentHealthy Volunteers / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections3
1CompletedTreatmentHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
1CompletedTreatmentHypertriglyceridemias1
1RecruitingPreventionHuman Immunodeficiency Virus (HIV) Infections1
1RecruitingTreatmentMetastatic Colorectal Cancers / MSS1
1TerminatedScreeningHuman Immunodeficiency Virus (HIV) Infections1
1TerminatedTreatmentHealthy Volunteers1
1WithdrawnPreventionHuman Immunodeficiency Virus (HIV) Infections1
1, 2Active Not RecruitingTreatmentGraft Versus Host Disease (GVHD) / Hematopoietic Stem Cell Transplantation (HSCT)1
1, 2CompletedTreatmentAcute HIV Infection1
1, 2RecruitingPreventionDiagnoses That Require Stem Cell Transplant / Graft Versus Host Disease (GVHD)1
2Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV)2
2CompletedNot AvailableHealthy Volunteers1
2CompletedBasic ScienceHuman Immunodeficiency Virus Type 1 (HIV-1)1
2CompletedPreventionChronic Chronic myelogenous leukemia / Chronic Lymphocytic Leukaemia (CLL) / Follicular Lymphoma (FL) / Leukemia, Acute / Lymphoma, B-Cell / Lymphoma, Hodgkins / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Myelodysplasia / Small Lymphocytic Lymphoma (SLL)1
2CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHematologic Malignancy Requiring Allogeneic Stem-cell Transplantation / Malignancies, Hematologic1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections3
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Infection, Human Immunodeficiency Virus I1
2CompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
2CompletedTreatmentInfection, Human Immunodeficiency Virus I1
2RecruitingPreventionGraft Versus Host Disease (GVHD) / Hematopoietic Stem Cell Transplantation (HSCT)1
2RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kidney Diseases1
2TerminatedTreatmentHuman Immunodeficiency Virus (HIV) / Lipohypertrophy1
2TerminatedTreatmentRheumatoid Arthritis1
2Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2, 3CompletedTreatmentAcute HIV Infection1
2, 3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections4
2, 3RecruitingTreatmentAIDS-Related Dementia Complex1
2, 3RecruitingTreatmentHepatic Steatosis / HIV-1-infection1
2, 3RecruitingTreatmentStrokes1
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Infection, Human Immunodeficiency Virus I1
3CompletedTreatmentAdvanced HIV Infection / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentCardiovascular Disease (CVD) / Human Immunodeficiency Virus (HIV) Infections / Inflammatory Reaction1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections3
3CompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
3CompletedTreatmentInfection, Human Immunodeficiency Virus I1
3No Longer AvailableNot AvailableHuman Immunodeficiency Virus (HIV)1
3TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3TerminatedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
3WithdrawnTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
4Active Not RecruitingOtherHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
4CompletedNot AvailableHealthy Volunteers1
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) / Proteinuria1
4CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS)1
4CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV)1
4CompletedTreatmentAtherosclerosis / Cardiovascular Risk Factors / HIV Infection With Other Conditions / Inflammatory Reaction1
4CompletedTreatmentHIV Associated Neurocognitive Disorders (HAND) / Human Immunodeficiency Virus (HIV)1
4CompletedTreatmentHIV Coinfection1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV)3
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections8
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
4RecruitingTreatmentCCR5 / HIV Reservoir / Human Immunodeficiency Virus (HIV) / Transplant, Kidney1
4RecruitingTreatmentHepatitis C Viral Infection / Human Immunodeficiency Virus (HIV)1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4TerminatedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
4TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections2
4Unknown StatusTreatmentAcquired Immune Deficiency Syndrome (AIDS) / HIV-1 Adults Patients / Triple Class Failure1
4Unknown StatusTreatmentEndothelial Dysfunction1
4Unknown StatusTreatmentInfection, Human Immunodeficiency Virus I1
4WithdrawnTreatmentChronic Hepatitis C Virus (HCV) Infection / Human Immunodeficiency Virus (HIV) / Viral Hepatitis B1
Not AvailableActive Not RecruitingNot AvailableCCR5-tropic HIV-1 Infection1
Not AvailableActive Not RecruitingNot AvailableHuman Immunodeficiency Virus (HIV)1
Not AvailableActive Not RecruitingTreatmentChronic Infection / Human Immunodeficiency Virus (HIV)1
Not AvailableCompletedNot AvailableAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedNot AvailableCardiovascular Disease (CVD)1
Not AvailableCompletedNot AvailableColorectal Cancers / Hepatic Metastases / Neoplasms Metastasis1
Not AvailableCompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedNot AvailableHuman Immunodeficiency Virus Type 1 (HIV-1)1
Not AvailableCompletedNot AvailableInfection, Human Immunodeficiency Virus I1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections3
Not AvailableNo Longer AvailableNot AvailableHuman Immunodeficiency Virus (HIV)1
Not AvailableTerminatedBasic ScienceSarcoidosis1
Not AvailableTerminatedPreventionHuman Immunodeficiency Virus (HIV)1
Not AvailableUnknown StatusPreventionHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections / Immune Reconstitution Inflammatory Syndrome1
Not AvailableUnknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableUnknown StatusTreatmentKaposi s Sarcoma (KS)1

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
TabletOral150 mg
TabletOral300 mg
Tablet, film coatedOral150 mg
Tablet, film coatedOral300 mg
SolutionOral20 mg/1mL
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)
CA2350073No2007-04-172019-12-23Canada
CA2408909No2006-06-272021-05-09Canada
US6586430No1999-12-012019-12-01Us
US6667314No2001-08-062021-08-06Us
US7368460No2002-11-252022-11-25Us
US7576097No2001-05-252021-05-25Us

Properties

State
Solid
Experimental Properties
Not 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 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/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Tropane alkaloid / Cyclohexyl halide / Aralkylamine / Monocyclic benzene moiety / Piperidine / N-alkylpyrrolidine / Benzenoid / Azole / Pyrrolidine / 1,2,4-triazole
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, azabicycloalkane, monocarboxylic acid amide, triazoles (CHEBI:63608)

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 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. [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 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. [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]

Drug created on September 11, 2007 19:14 / Updated on October 21, 2018 20:32