Identification

Summary

Nelfinavir is a viral protease inhibitor used in the treatment of HIV infection.

Brand Names
Viracept
Generic Name
Nelfinavir
DrugBank Accession Number
DB00220
Background

Nelfinavir is a potent HIV-1 protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. Nelfinavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.6

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 567.782
Monoisotopic: 567.313077633
Chemical Formula
C32H45N3O4S
Synonyms
  • Nelfinavir
External IDs
  • AG1343

Pharmacology

Indication

Used in combination with other antiviral drugs in the treatment of HIV in both adults and children.6

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Nelfinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Nelfinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.

Mechanism of action

HIV viral protease is an important enzyme for HIV maturation and pathogenicity since HIV produces its structural and key proteins in the form of a polyprotein that needs to be cleaved by a protease.2 HIV protease is synthesized as part of the Gag-pol polyprotein, where Gag encodes for the capsid and matrix protein to form the outer protein shell, and Pol encodes for the reverse transcriptase and integrase protein to synthesize and incorporate its genome into host cells.2,3 The Gag-pol polyprotein undergoes proteolytic cleavage by HIV protease to produce 66 molecular species which will assume conformational changes to become fully active.2 Inhibition of protease, therefore, prevents HIV virion from fully maturing and becoming infective.2

Nelfinavir is a competitive inhibitor of the HIV protease by reversibly binding to the active site of the enzyme, preventing it from interacting with its substrate to produce mature and infectious viral particles.6,7

TargetActionsOrganism
AHIV-1 protease
inhibitor
Human Immunodeficiency Virus
Absorption

Well absorbed following oral administration.

Volume of distribution

The apparent volume of distribution following oral administration of nelfinavir was 2-7 L/kg.6

Protein binding

Nelfinavir in serum is extensively protein-bound (>98%).6

Metabolism

Unchanged nelfinavir comprised 82-86% of the total plasma radioactivity after a single oral 750 mg dose of 14C-nelfinavir. In vitro, multiple cytochrome P-450 enzymes including CYP3A and CYP2C19 are responsible for the metabolism of nelfinavir. One major and several minor oxidative metabolites were found in plasma. The major oxidative metabolite has in vitro antiviral activity comparable to the parent drug.6

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Route of elimination

The majority (87%) of an oral 750 mg dose containing 14C-nelfinavir was recovered in the feces; fecal radioactivity consisted of numerous oxidative metabolites (78%) and unchanged nelfinavir (22%). Only 1–2% of the dose was recovered in urine, of which unchanged nelfinavir was the major component.6

Half-life

The terminal half-life in plasma was typically 3.5 to 5 hours.6

Clearance

Oral clearance estimates after single doses (24-33 L/h) and multiple doses (26-61 L/h) indicate that nelfinavir is a drug with medium to high hepatic bioavailability.7

Adverse Effects
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Toxicity

Carcinogenicity studies in mice and rats were conducted with nelfinavir at oral doses up to 1000 mg/kg/day. No evidence of a tumorigenic effect was noted in mice at systemic exposures (Cmax) up to 9-fold those measured in humans at the recommended therapeutic dose (750 mg TID or 1250 mg BID). In rats, thyroid follicular cell adenomas and carcinomas were increased in males at 300 mg/kg/day and higher and in females at 1000 mg/kg/day. Systemic exposures (Cmax) at 300 and 1000 mg/kg/day were 1- to 3-fold, respectively, those measured in humans at the recommended therapeutic dose. Repeated administration of nelfinavir to rats produced effects consistent with hepatic microsomal enzyme induction and increased thyroid hormone deposition; these effects predispose rats, but not humans, to thyroid follicular cell neoplasms. Nelfinavir showed no evidence of mutagenic or clastogenic activity in a battery of in vitro and in vivo genetic toxicology assays. These studies included bacterial mutation assays in S. typhimurium and E. coli, a mouse lymphoma tyrosine kinase assay, a chromosomal aberration assay in human lymphocytes, and an in vivo mouse bone marrow micronucleus assay.6

Nelfinavir produced no effects on either male or female mating and fertility or embryo survival in rats at systemic exposures comparable to the human therapeutic exposure.6

Human experience of acute overdose with nelfinavir is limited. There is no specific antidote for overdose with VIRACEPT. If indicated, elimination of unabsorbed drug should be achieved by emesis or gastric lavage. Administration of activated charcoal may also be used to aid the removal of unabsorbed drug. Since nelfinavir is highly protein-bound, dialysis is unlikely to significantly remove the drug from blood.6

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
1,2-BenzodiazepineThe metabolism of 1,2-Benzodiazepine can be decreased when combined with Nelfinavir.
AbacavirThe metabolism of Abacavir can be increased when combined with Nelfinavir.
AbametapirThe serum concentration of Nelfinavir can be increased when it is combined with Abametapir.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Nelfinavir.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Nelfinavir.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Nelfinavir.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Nelfinavir.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Nelfinavir.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Nelfinavir.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Nelfinavir.
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Food Interactions
  • Take with food. Food increases exposure and decreases pharmacokinetic variability.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Nelfinavir mesylate98D603VP8V159989-65-8NQHXCOAXSHGTIA-SKXNDZRYSA-N
Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ViraceptTablet, film coated625 mg/1OralAGOURON2003-04-30Not applicableUS flag
ViraceptTablet, film coated250 mg/1OralH.J. Harkins Company1997-03-14Not applicableUS flag
ViraceptTablet, film coated625 mg/1OralRemedy Repack2013-03-272014-03-27US flag
ViraceptTablet, film coated250 mg/1OralPD-Rx Pharmaceuticals, Inc.1997-03-142019-09-12US flag
ViraceptTablet, film coated625 mg/1OralState of Florida DOH Central Pharmacy2009-07-01Not applicableUS flag
ViraceptTablet, film coated250 mg/1OralAGOURON1997-03-14Not applicableUS flag
ViraceptTablet625 mgOralPfizer Canada Ulc2004-08-112021-11-12Canada flag
ViraceptTablet, film coated250 mg/1OralPhysicians Total Care, Inc.1997-03-142002-06-30US flag
ViraceptPowder50 mg/1gOralAGOURON PHARMACEUTICALS, INC.2007-08-282007-08-28US flag
Viracept -250mgTablet250 mgOralPfizer Canada Ulc1998-09-212022-06-02Canada flag

Categories

ATC Codes
J05AE04 — Nelfinavir
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acid amides
Alternative Parents
o-Toluamides / Piperidinecarboxamides / Benzamides / Thiophenol ethers / Ortho cresols / Benzoyl derivatives / 1-hydroxy-2-unsubstituted benzenoids / 1-hydroxy-4-unsubstituted benzenoids / Alkylarylthioethers / Trialkylamines
show 9 more
Substituents
1,2-aminoalcohol / 1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / 2-piperidinecarboxamide / Alcohol / Alkylarylthioether / Alpha-amino acid amide / Amine / Aromatic heteropolycyclic compound / Aryl thioether
show 31 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary amino compound, secondary alcohol, aryl sulfide, phenols, benzamides, organic heterobicyclic compound (CHEBI:7496)
Affected organisms
  • Human Immunodeficiency Virus

Chemical Identifiers

UNII
HO3OGH5D7I
CAS number
159989-64-7
InChI Key
QAGYKUNXZHXKMR-HKWSIXNMSA-N
InChI
InChI=1S/C32H45N3O4S/c1-21-25(15-10-16-28(21)36)30(38)33-26(20-40-24-13-6-5-7-14-24)29(37)19-35-18-23-12-9-8-11-22(23)17-27(35)31(39)34-32(2,3)4/h5-7,10,13-16,22-23,26-27,29,36-37H,8-9,11-12,17-20H2,1-4H3,(H,33,38)(H,34,39)/t22-,23+,26-,27-,29+/m0/s1
IUPAC Name
(3S,4aS,8aS)-N-tert-butyl-2-[(2R,3R)-2-hydroxy-3-[(3-hydroxy-2-methylphenyl)formamido]-4-(phenylsulfanyl)butyl]-decahydroisoquinoline-3-carboxamide
SMILES
[H][C@@]12CCCC[C@]1([H])CN(C[C@@H](O)[C@H](CSC1=CC=CC=C1)NC(=O)C1=C(C)C(O)=CC=C1)[C@@H](C2)C(=O)NC(C)(C)C

References

Synthesis Reference
US5461154
General References
  1. Kaldor SW, Kalish VJ, Davies JF 2nd, Shetty BV, Fritz JE, Appelt K, Burgess JA, Campanale KM, Chirgadze NY, Clawson DK, Dressman BA, Hatch SD, Khalil DA, Kosa MB, Lubbehusen PP, Muesing MA, Patick AK, Reich SH, Su KS, Tatlock JH: Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease. J Med Chem. 1997 Nov 21;40(24):3979-85. [Article]
  2. Konnyu B, Sadiq SK, Turanyi T, Hirmondo R, Muller B, Krausslich HG, Coveney PV, Muller V: Gag-Pol processing during HIV-1 virion maturation: a systems biology approach. PLoS Comput Biol. 2013;9(6):e1003103. doi: 10.1371/journal.pcbi.1003103. Epub 2013 Jun 6. [Article]
  3. Takagi S, Momose F, Morikawa Y: FRET analysis of HIV-1 Gag and GagPol interactions. FEBS Open Bio. 2017 Oct 19;7(11):1815-1825. doi: 10.1002/2211-5463.12328. eCollection 2017 Nov. [Article]
  4. McDonald MG, Au NT, Rettie AE: P450-Based Drug-Drug Interactions of Amiodarone and its Metabolites: Diversity of Inhibitory Mechanisms. Drug Metab Dispos. 2015 Nov;43(11):1661-9. doi: 10.1124/dmd.115.065623. Epub 2015 Aug 21. [Article]
  5. Nelfinavir FDA label [Link]
  6. FDA Approved Drug Products: VIRACEPT (nelfinavir mesylate) tablets and powder [Link]
  7. Health Canada Approved Drug Products: VIRACEPT (nelfinavir mesylate) tablets and powder [Link]
  8. Cayman Chemical: Nelfinavir MSDS [Link]
Human Metabolome Database
HMDB0014365
KEGG Drug
D08259
KEGG Compound
C07257
PubChem Compound
64143
PubChem Substance
46507719
ChemSpider
57718
BindingDB
50061306
RxNav
134527
ChEBI
7496
ChEMBL
CHEMBL584
ZINC
ZINC000003833846
Therapeutic Targets Database
DAP000705
PharmGKB
PA450606
PDBe Ligand
1UN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Nelfinavir
PDB Entries
1ohr / 2pym / 2pyn / 2q63 / 2q64 / 2qak / 2r5q / 3ekx / 3el0 / 3el5
show 1 more
FDA label
Download (294 KB)
MSDS
Download (56.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedDiagnosticCardiovascular Disease (CVD) / HIV Lipodystrophy Syndrome1
4CompletedDiagnosticHuman Immunodeficiency Virus (HIV) Infections / Lipodystrophies1
4CompletedTreatmentHealthy Subjects (HS)2
4CompletedTreatmentHepatitis C Virus (HCV) Infection / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections3
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis (TB)1
4Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3CompletedPreventionDisease Transmission, Vertical / Human Immunodeficiency Virus (HIV) Infections / Vertical Human Immunodeficiency Virus Transmission1
3CompletedTreatmentAIDS Associated Nephropathy / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections9

Pharmacoeconomics

Manufacturers
  • Agouron pharmaceuticals inc
Packagers
  • Agouron Pharmaceuticals Inc.
  • A-S Medication Solutions LLC
  • Cardinal Health
  • Dept Health Central Pharmacy
  • Dispensing Solutions
  • Goedecke GmbH
  • H.J. Harkins Co. Inc.
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Patheon Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pfizer Inc.
  • Physicians Total Care Inc.
  • Quality Care
  • Remedy Repack
  • St Mary's Medical Park Pharmacy
  • Watson Pharmaceuticals
Dosage Forms
FormRouteStrength
PowderOral
PowderOral50 mg/1g
TabletOral
TabletOral625 mg
Tablet, film coatedOral
Tablet, film coatedOral250 mg/1
Tablet, film coatedOral625 mg/1
TabletOral250 mg
PowderOral50 mg / g
Prices
Unit descriptionCostUnit
Viracept 625 mg tablet11.24USD tablet
Viracept 250 mg tablet3.46USD tablet
Viracept 50 mg/gm Powder0.54USD gm
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5484926No1996-01-162014-04-07US flag
CA2173328No1999-08-312014-10-07Canada flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)349.84 °CNot Available
water solubilitySlightly solubleNot Available
logP6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00191 mg/mLALOGPS
logP4.61ALOGPS
logP4.72Chemaxon
logS-5.5ALOGPS
pKa (Strongest Acidic)9.32Chemaxon
pKa (Strongest Basic)8.18Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count4Chemaxon
Polar Surface Area101.9 Å2Chemaxon
Rotatable Bond Count10Chemaxon
Refractivity162.67 m3·mol-1Chemaxon
Polarizability63.81 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.7472
Blood Brain Barrier-0.9659
Caco-2 permeable-0.7148
P-glycoprotein substrateSubstrate0.9332
P-glycoprotein inhibitor IInhibitor0.8121
P-glycoprotein inhibitor IIInhibitor0.7572
Renal organic cation transporterNon-inhibitor0.8178
CYP450 2C9 substrateNon-substrate0.7482
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.7408
CYP450 1A2 substrateNon-inhibitor0.9085
CYP450 2C9 inhibitorNon-inhibitor0.7994
CYP450 2D6 inhibitorNon-inhibitor0.8071
CYP450 2C19 inhibitorNon-inhibitor0.6335
CYP450 3A4 inhibitorInhibitor0.5465
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8977
Ames testNon AMES toxic0.8008
CarcinogenicityNon-carcinogens0.8547
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4704 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9786
hERG inhibition (predictor II)Inhibitor0.785
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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

Targets

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Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
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Kind
Protein
Organism
Human Immunodeficiency Virus
Pharmacological action
Yes
Actions
Inhibitor
General Function
Aspartic-type endopeptidase activity
Specific Function
Not Available
Gene Name
HIV-1 protease
Uniprot ID
O90777
Uniprot Name
HIV-1 protease
Molecular Weight
10724.61 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. Garriga C, Perez-Elias MJ, Delgado R, Ruiz L, Najera R, Pumarola T, Alonso-Socas Mdel M, Garcia-Bujalance S, Menendez-Arias L: Mutational patterns and correlated amino acid substitutions in the HIV-1 protease after virological failure to nelfinavir- and lopinavir/ritonavir-based treatments. J Med Virol. 2007 Nov;79(11):1617-28. [Article]
  4. Wittayanarakul K, Hannongbua S, Feig M: Accurate prediction of protonation state as a prerequisite for reliable MM-PB(GB)SA binding free energy calculations of HIV-1 protease inhibitors. J Comput Chem. 2008 Apr 15;29(5):673-85. [Article]
  5. Dandache S, Sevigny G, Yelle J, Stranix BR, Parkin N, Schapiro JM, Wainberg MA, Wu JJ: In vitro antiviral activity and cross-resistance profile of PL-100, a novel protease inhibitor of human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2007 Nov;51(11):4036-43. Epub 2007 Jul 16. [Article]
  6. Perez MA, Fernandes PA, Ramos MJ: Drug design: new inhibitors for HIV-1 protease based on Nelfinavir as lead. J Mol Graph Model. 2007 Oct;26(3):634-42. Epub 2007 Mar 24. [Article]
  7. Velazquez-Campoy A, Kiso Y, Freire E: The binding energetics of first- and second-generation HIV-1 protease inhibitors: implications for drug design. Arch Biochem Biophys. 2001 Jun 15;390(2):169-75. [Article]
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  9. De Clercq E: Emerging anti-HIV drugs. Expert Opin Emerg Drugs. 2005 May;10(2):241-73. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
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. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Lillibridge JH, Liang BH, Kerr BM, Webber S, Quart B, Shetty BV, Lee CA: Characterization of the selectivity and mechanism of human cytochrome P450 inhibition by the human immunodeficiency virus-protease inhibitor nelfinavir mesylate. Drug Metab Dispos. 1998 Jul;26(7):609-16. [Article]
  3. Hsyu PH, Schultz-Smith MD, Lillibridge JH, Lewis RH, Kerr BM: Pharmacokinetic interactions between nelfinavir and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors atorvastatin and simvastatin. Antimicrob Agents Chemother. 2001 Dec;45(12):3445-50. doi: 10.1128/AAC.45.12.3445-3450.2001. [Article]
  4. Granfors MT, Wang JS, Kajosaari LI, Laitila J, Neuvonen PJ, Backman JT: Differential inhibition of cytochrome P450 3A4, 3A5 and 3A7 by five human immunodeficiency virus (HIV) protease inhibitors in vitro. Basic Clin Pharmacol Toxicol. 2006 Jan;98(1):79-85. doi: 10.1111/j.1742-7843.2006.pto_249.x. [Article]
  5. Flockhart Table of Drug Interactions [Link]
  6. Nelfinavir FDA label [Link]
  7. Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  8. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Oxygen binding
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 oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Granfors MT, Wang JS, Kajosaari LI, Laitila J, Neuvonen PJ, Backman JT: Differential inhibition of cytochrome P450 3A4, 3A5 and 3A7 by five human immunodeficiency virus (HIV) protease inhibitors in vitro. Basic Clin Pharmacol Toxicol. 2006 Jan;98(1):79-85. doi: 10.1111/j.1742-7843.2006.pto_249.x. [Article]
  2. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Oxygen binding
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 oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Granfors MT, Wang JS, Kajosaari LI, Laitila J, Neuvonen PJ, Backman JT: Differential inhibition of cytochrome P450 3A4, 3A5 and 3A7 by five human immunodeficiency virus (HIV) protease inhibitors in vitro. Basic Clin Pharmacol Toxicol. 2006 Jan;98(1):79-85. doi: 10.1111/j.1742-7843.2006.pto_249.x. [Article]
  2. Hirt D, Mentre F, Tran A, Rey E, Auleley S, Salmon D, Duval X, Treluyer JM: Effect of CYP2C19 polymorphism on nelfinavir to M8 biotransformation in HIV patients. Br J Clin Pharmacol. 2008 Apr;65(4):548-57. doi: 10.1111/j.1365-2125.2007.03039.x. Epub 2007 Oct 8. [Article]
  3. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Hesse LM, von Moltke LL, Shader RI, Greenblatt DJ: Ritonavir, efavirenz, and nelfinavir inhibit CYP2B6 activity in vitro: potential drug interactions with bupropion. Drug Metab Dispos. 2001 Feb;29(2):100-2. [Article]
  2. Tanabe M, Hashimoto M, Ono H: Imidazoline I(1) receptor-mediated reduction of muscle rigidity in the reserpine-treated murine model of Parkinson's disease. Eur J Pharmacol. 2008 Jul 28;589(1-3):102-5. doi: 10.1016/j.ejphar.2008.06.013. Epub 2008 Jun 7. [Article]
  3. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
  4. Walsky RL, Astuccio AV, Obach RS: Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol. 2006 Dec;46(12):1426-38. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Kattel K, Evande R, Tan C, Mondal G, Grem JL, Mahato RI: Impact of CYP2C19 polymorphism on the pharmacokinetics of nelfinavir in patients with pancreatic cancer. Br J Clin Pharmacol. 2015 Aug;80(2):267-75. doi: 10.1111/bcp.12620. Epub 2015 Jun 11. [Article]
  3. Dixit V, Hariparsad N, Li F, Desai P, Thummel KE, Unadkat JD: Cytochrome P450 enzymes and transporters induced by anti-human immunodeficiency virus protease inhibitors in human hepatocytes: implications for predicting clinical drug interactions. Drug Metab Dispos. 2007 Oct;35(10):1853-9. Epub 2007 Jul 16. [Article]
  4. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inducer
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inducer
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Kirby BJ, Collier AC, Kharasch ED, Dixit V, Desai P, Whittington D, Thummel KE, Unadkat JD: Complex drug interactions of HIV protease inhibitors 2: in vivo induction and in vitro to in vivo correlation of induction of cytochrome P450 1A2, 2B6, and 2C9 by ritonavir or nelfinavir. Drug Metab Dispos. 2011 Dec;39(12):2329-37. doi: 10.1124/dmd.111.038646. Epub 2011 Sep 19. [Article]
  2. Liedtke MD, Rathbun RC: Warfarin-antiretroviral interactions. Ann Pharmacother. 2009 Feb;43(2):322-8. doi: 10.1345/aph.1L497. Epub 2009 Feb 5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. von Moltke LL, Greenblatt DJ, Duan SX, Daily JP, Harmatz JS, Shader RI: Inhibition of desipramine hydroxylation (Cytochrome P450-2D6) in vitro by quinidine and by viral protease inhibitors: relation to drug interactions in vivo. J Pharm Sci. 1998 Oct;87(10):1184-9. doi: 10.1021/js980197h. [Article]
  2. Lillibridge JH, Liang BH, Kerr BM, Webber S, Quart B, Shetty BV, Lee CA: Characterization of the selectivity and mechanism of human cytochrome P450 inhibition by the human immunodeficiency virus-protease inhibitor nelfinavir mesylate. Drug Metab Dispos. 1998 Jul;26(7):609-16. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Bocedi A, Notaril S, Narciso P, Bolli A, Fasano M, Ascenzi P: Binding of anti-HIV drugs to human serum albumin. IUBMB Life. 2004 Oct;56(10):609-14. [Article]
  2. Bocedi A, Notari S, Menegatti E, Fanali G, Fasano M, Ascenzi P: Allosteric modulation of anti-HIV drug and ferric heme binding to human serum albumin. FEBS J. 2005 Dec;272(24):6287-96. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Motoya T, Thevanayagam LN, Blaschke TF, Au S, Stone JA, Jayewardene AL, Chi J, Aweeka FT: Characterization of nelfinavir binding to plasma proteins and the lack of drug displacement interactions. HIV Med. 2006 Mar;7(2):122-8. doi: 10.1111/j.1468-1293.2006.00356.x. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
Inducer
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Perloff MD, von Moltke LL, Fahey JM, Daily JP, Greenblatt DJ: Induction of P-glycoprotein expression by HIV protease inhibitors in cell culture. AIDS. 2000 Jun 16;14(9):1287-9. [Article]
  2. Choo EF, Leake B, Wandel C, Imamura H, Wood AJ, Wilkinson GR, Kim RB: Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab Dispos. 2000 Jun;28(6):655-60. [Article]
  3. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [Article]
  4. Kim RB, Fromm MF, Wandel C, Leake B, Wood AJ, Roden DM, Wilkinson GR: The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest. 1998 Jan 15;101(2):289-94. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Zhang L, Gorset W, Washington CB, Blaschke TF, Kroetz DL, Giacomini KM: Interactions of HIV protease inhibitors with a human organic cation transporter in a mammalian expression system. Drug Metab Dispos. 2000 Mar;28(3):329-34. [Article]
  2. Jung N, Lehmann C, Rubbert A, Schomig E, Fatkenheuer G, Hartmann P, Taubert D: Organic cation transporters OCT1 and OCT2 determine the accumulation of lamivudine in CD4 cells of HIV-infected patients. Infection. 2013 Apr;41(2):379-85. doi: 10.1007/s15010-012-0308-8. Epub 2012 Aug 9. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB: OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos. 1999 Aug;27(8):866-71. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Gupta A, Zhang Y, Unadkat JD, Mao Q: HIV protease inhibitors are inhibitors but not substrates of the human breast cancer resistance protein (BCRP/ABCG2). J Pharmacol Exp Ther. 2004 Jul;310(1):334-41. Epub 2004 Mar 8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Tirona RG, Leake BF, Wolkoff AW, Kim RB: Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. J Pharmacol Exp Ther. 2003 Jan;304(1):223-8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [Article]

Drug created at June 13, 2005 13:24 / Updated at December 01, 2022 23:18