Nelfinavir

Targets (1)Enzymes (8)Carriers (1)Transporters (8)Biointeractions (22)

Identification

Name
Nelfinavir
Accession Number
DB00220  (APRD00003)
Type
Small Molecule
Groups
Approved
Description

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.

Structure
Thumb
3D
Similar Structures
Synonyms
  • Nelfinavir
External IDs
AG1343
Product Ingredients
IngredientUNIICASInChI Key
Nelfinavir mesylate98D603VP8V159989-65-8NQHXCOAXSHGTIA-SKXNDZRYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ViraceptPowder50 mg/1gOralAGOURON PHARMACEUTICALS, INC.2007-08-282007-08-28Us
ViraceptTablet625 mgOralPfizer2004-08-11Not applicableCanada
ViraceptTablet, film coated250 mg/1OralAgouron Pharmaceuticals1997-03-14Not applicableUs
ViraceptTablet, film coated250 mg/1OralPhysicians Total Care, Inc.1997-03-142002-06-30Us
ViraceptTablet, film coated625 mg/1OralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs53808 080920180907 15195 wvfb52
ViraceptTablet, film coated250 mg/1OralH.J. Harkins Company1997-03-14Not applicableUs63010 0010 30 nlmimage10 691934d9
ViraceptTablet, film coated250 mg/1OralPD-Rx Pharmaceuticals, Inc.1997-03-14Not applicableUs
ViraceptTablet, film coated625 mg/1OralAgouron Pharmaceuticals2003-04-30Not applicableUs
ViraceptTablet, film coated625 mg/1OralRemedy Repack2013-03-272014-03-27Us63010 0027 70 nlmimage10 aa3dd57e
Viracept -250mgTablet250 mgOralPfizer1998-09-21Not applicableCanada
Categories
UNII
HO3OGH5D7I
CAS number
159989-64-7
Weight
Average: 567.782
Monoisotopic: 567.313077633
Chemical Formula
C32H45N3O4S
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

Pharmacology

Indication

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

Associated Conditions
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

Nelfinavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.

TargetActionsOrganism
AHIV-1 protease
inhibitor
Human Immunodeficiency Virus
Absorption

Well absorbed following oral administration.

Volume of distribution
  • 2 to 7 L/kg
Protein binding

>98%

Metabolism

Primarily hepatic via cytochrome P450 (CYP450) enzymes. CYP3A and CYP2C19 appear to be the predominant enzymes that metabolize nelfinavir in humans. One major and several minor metabolites are found in plasma; the major oxidative metabolite has in vitro antiviral activity comparable to that of the parent drug.

Route of elimination

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

Half life

3.5 - 5 hours

Clearance
Not Available
Toxicity

Oral LD50 is over 5g/kg in rats. Side effects include thirst and hunger, unexplained weight loss, increased urination, fatigue, and dry, itchy skin.

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

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Nelfinavir.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Nelfinavir.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Nelfinavir.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Nelfinavir.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Nelfinavir.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Nelfinavir.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Nelfinavir.
6-Deoxyerythronolide BThe metabolism of Nelfinavir can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Nelfinavir.
7-ethyl-10-hydroxycamptothecinThe metabolism of 7-ethyl-10-hydroxycamptothecin can be decreased when combined with Nelfinavir.
Food Interactions
  • Food significantly increases absorption (2 to 3 times).
  • Take with food.

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. [PubMed:9397180]
External Links
Human Metabolome Database
HMDB0014365
KEGG Drug
D08259
KEGG Compound
C07257
PubChem Compound
64143
PubChem Substance
46507719
ChemSpider
57718
BindingDB
518
ChEBI
7496
ChEMBL
CHEMBL584
Therapeutic Targets Database
DAP000705
PharmGKB
PA450606
HET
1UN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Nelfinavir
ATC Codes
J05AE04 — Nelfinavir
AHFS Codes
  • 08:18.08.08 — HIV Protease Inhibitors
PDB Entries
1ohr / 2pym / 2pyn / 2q63 / 2q64 / 2qak / 2r5q / 3ekx / 3el0 / 3el5
FDA label
Download (294 KB)
MSDS
Download (56.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0TerminatedTreatmentCastleman's Disease / EBV / Kaposi s Sarcoma (KS) / Lymphoma, Hodgkins / Malignant Neoplasm of Nasopharynx / Malignant Neoplasm of Stomach / Non-Hodgkin's Lymphoma (NHL)1
1Active Not RecruitingNot AvailableGliomas1
1Active Not RecruitingTreatmentAdenocarcinoma of the Pancreas / Stage III Pancreatic Cancer1
1Active Not RecruitingTreatmentBrain and Central Nervous System Tumors1
1Active Not RecruitingTreatmentCancer of the Ovary / Carcinoid tumour of the gastrointestinal tract / Colorectal Cancers / Head and Neck Carcinoma / Islet Cell Tumor / Lung Cancers / Metastatic Cancers / Neuroendocrine Carcinoma of the Skin / Pheochromocytomas / Sarcomas / Unspecified Adult Solid Tumor, Protocol Specific1
1Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1CompletedTreatmentCervical Cancers1
1CompletedTreatmentGlioblastomas1
1CompletedTreatmentHIV Seronegativity / Human Immunodeficiency Virus (HIV) Infections / Lipodystrophies1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections12
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Pregnancy1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis Infection1
1CompletedTreatmentImmune Response1
1CompletedTreatmentLeukemias / Malignant Lymphomas / Mature T-cell and Nk-cell Neoplasms / Multiple Myeloma and Plasma Cell Neoplasm1
1CompletedTreatmentMalignancies / Renal Cell Adenocarcinoma1
1CompletedTreatmentSepsis1
1CompletedTreatmentTumors, Solid1
1RecruitingTreatmentUterine Cervix Cancer1
1TerminatedPreventionCardiopulmonary Bypass1
1TerminatedTreatmentNeoplasms, Pancreatic1
1WithdrawnTreatmentMalignant Lymphomas / Neoplasms1
1, 2Active Not RecruitingTreatmentLung Cancers1
1, 2Active Not RecruitingTreatmentMultiple Myeloma (MM)1
1, 2CompletedTreatmentCarcinoma, Colorectal / Colorectal Cancers / Colorectal Tumors / Neoplasms, Colorectal1
1, 2RecruitingTreatmentPancreatic Neoplasms (Locally Advanced Non-metastatic)1
1, 2TerminatedTreatmentAdult Liposarcoma / Recurrent Adult Soft Tissue Sarcoma / Stage III Adult Soft Tissue Sarcoma / Stage IV Adult Soft Tissue Sarcoma1
1, 2WithdrawnTreatmentLung Cancers1
2Active Not RecruitingTreatmentAdenocarcinoma of the Pancreas / Resectable Pancreatic Cancers / Resectable Pancreatic Carcinoma / Stage I Pancreatic Cancer / Stage IA Pancreatic Cancer / Stage IB Pancreatic Cancer / Stage II Pancreatic Cancer / Stage IIA Pancreatic Cancer / Stage IIB Pancreatic Cancer / Stage III Pancreatic Cancer1
2Active Not RecruitingTreatmentOligometastases1
2CompletedTreatmentCarcinoma, Adenoid Cystic / Neoplasms, Head and Neck1
2CompletedTreatmentCytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections16
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Infection, Mycobacterium Avium-Intracellulare1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Kaposi s Sarcoma (KS)1
2CompletedTreatmentPlasma Cell Myeloma1
2CompletedTreatmentSarcomas1
2CompletedTreatmentSystemic Lupus Erythematosus (SLE)1
2RecruitingDiagnosticStage III, IVa, or IVb Squamous Cell Carcinoma of the Oral Cavity, Oropharynx, Larynx, or Hypopharynx1
2RecruitingTreatmentCervical Dysplasia1
2RecruitingTreatmentMetastatic Renal Cell Cancer / Recurrent Melanoma / Recurrent Non-Small Cell Lung Carcinoma / Renal Cell Carcinoma Recurrent / Stage IV Cutaneous Melanoma AJCC v6 and v7 / Stage IV Non-Small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer AJCC v7 / Stage IV Renal Cell Cancer / Stage IV Renal Cell Cancer AJCC V7 / Stage IV Skin Melanoma1
2RecruitingTreatmentRecurrent Kaposi's Sarcoma / Skin Kaposi Sarcoma1
2SuspendedTreatmentHuman Immunodeficiency Virus (HIV) Infections2
2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2WithdrawnTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2, 3CompletedTreatmentHuman 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
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Pregnancy1
3Not Yet RecruitingTreatmentCarcinoma Cervix, Stage III1
3TerminatedPreventionSevere or persistent diarrhea1
3TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections3
4CompletedDiagnosticCardiovascular Disease (CVD) / HIV-Associated Lipodystrophy Syndrome1
4CompletedDiagnosticHuman Immunodeficiency Virus (HIV) Infections / Lipodystrophies1
4CompletedTreatmentHealthy Volunteers2
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections2
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis Infection1
4Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections20
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Infection, Mycobacterium Avium-Intracellulare1
Not AvailableTerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableUnknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections1

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
PowderOral50 mg/1g
TabletOral625 mg
Tablet, film coatedOral250 mg/1
Tablet, film coatedOral625 mg/1
TabletOral250 mg
PowderOral50 mg
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)
US5484926No1996-01-162014-04-07Us
CA2173328No1999-08-312014-10-07Canada

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
Polarizability63.8 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

Taxonomy

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
Alpha-amino acid amide / Piperidinecarboxamide / 2-piperidinecarboxamide / Toluamide / Benzamide / O-toluamide / Benzoic acid or derivatives / Thiophenol ether / O-cresol / Benzoyl
show 31 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary amino compound, secondary alcohol, aryl sulfide, phenols, benzamides, organic heterobicyclic compound (CHEBI:7496)

Targets

Details1. HIV-1 protease
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. [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. 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. [PubMed:17854027]
  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. [PubMed:17849388]
  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. [PubMed:17638694]
  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. [PubMed:17459746]
  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. [PubMed:11396919]
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Details1. Cytochrome P450 2B6
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. [PubMed:11159797]
  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. [PubMed:18602099]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  4. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  5. 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. [PubMed:17101742]
Details2. Cytochrome P450 2C19
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Details3. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  4. Flockhart Table - Indiana University [Link]
Details4. Cytochrome P450 3A7
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  3. Flockhart Table - Indiana University [Link]
Details5. Cytochrome P450 3A5
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 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. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  4. Flockhart Table - Indiana University [Link]
Details6. Cytochrome P450 2D6
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. 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. [PubMed:9758674]
  3. 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. [PubMed:9660842]
Details7. UDP-glucuronosyltransferase 1-1
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]
Details8. Cytochrome P450 2C9
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
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. [PubMed:21930825]
  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. [PubMed:19196837]

Carriers

Details1. Serum albumin
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. [PubMed:15814459]
  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. [PubMed:16336266]

Transporters

Details1. Multidrug resistance protein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. [PubMed:10894301]
  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. [PubMed:10820137]
  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. [PubMed:12699389]
  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. [PubMed:9435299]
Details2. Solute carrier family 22 member 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. [PubMed:10681378]
  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. [PubMed:22875535]
Details3. Solute carrier organic anion transporter family member 1A2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. [PubMed:10421612]
Details4. ATP-binding cassette sub-family G member 2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. [PubMed:15007102]
Details5. Solute carrier organic anion transporter family member 1B1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. [PubMed:12490595]
Details6. Solute carrier organic anion transporter family member 1B3
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. [PubMed:22541068]
Details7. Solute carrier organic anion transporter family member 2B1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. [PubMed:22541068]
Details8. Bile salt export pump
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. [PubMed:24014644]

Drug created on June 13, 2005 07:24 / Updated on January 21, 2019 07:02