Identification

Name
Indinavir
Accession Number
DB00224  (APRD00069)
Type
Small Molecule
Groups
Approved
Description

A potent and specific HIV protease inhibitor that appears to have good oral bioavailability. [PubChem]

Structure
Thumb
Synonyms
  • (1(1S,2R),5(S))-2,3,5-Trideoxy-N-(2,3-dihydro-2-hydroxy-1H-inden-1-yl)-5-(2-(((1,1-dimethylethyl)amino)carbonyl)-4-(3-pyridinylmethyl)-1-piperazinyl)-2-(phenylmethyl)-D-erythro-pentonamide
  • Indinavir anhydrous
Product Ingredients
IngredientUNIICASInChI Key
Indinavir monohydrate5W6YA9PKKH180683-37-8XTYSXGHMTNTKFH-BDEHJDMKSA-N
Indinavir sulfate771H53976Q157810-81-6NUBQKPWHXMGDLP-BDEHJDMKSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CrixivanCapsule200 mgOralMerck Sharp & Dohme Limited1996-10-04Not applicableEu
CrixivanCapsule200 mgOralMerck Ltd.1996-09-262014-09-19Canada
CrixivanCapsule200 mg/1OralMerck Sharp & Dohme Limited1996-03-13Not applicableUs
CrixivanCapsule400 mg/1OralAvera McKennan Hospital2015-03-012018-07-09Us
CrixivanCapsule400 mg/1OralRebel Distributors1996-03-13Not applicableUs
CrixivanCapsule400 mgOralMerck Sharp & Dohme Limited1996-10-04Not applicableEu
CrixivanCapsule200 mgOralMerck Sharp & Dohme Limited1996-10-04Not applicableEu
CrixivanCapsule333 mg/1OralMerck & Co., Inc2006-08-072006-08-07Us
CrixivanCapsule400 mg/1OralStat Rx USA1996-03-13Not applicableUs
CrixivanCapsule400 mgOralMerck Ltd.1996-09-302016-11-01Canada
Categories
UNII
9MG78X43ZT
CAS number
150378-17-9
Weight
Average: 613.7895
Monoisotopic: 613.362805017
Chemical Formula
C36H47N5O4
InChI Key
CBVCZFGXHXORBI-PXQQMZJSSA-N
InChI
InChI=1S/C36H47N5O4/c1-36(2,3)39-35(45)31-24-40(22-26-12-9-15-37-21-26)16-17-41(31)23-29(42)19-28(18-25-10-5-4-6-11-25)34(44)38-33-30-14-8-7-13-27(30)20-32(33)43/h4-15,21,28-29,31-33,42-43H,16-20,22-24H2,1-3H3,(H,38,44)(H,39,45)/t28-,29+,31+,32-,33+/m1/s1
IUPAC Name
(2S)-1-[(2S,4R)-4-benzyl-2-hydroxy-4-{[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]carbamoyl}butyl]-N-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide
SMILES
CC(C)(C)NC(=O)[C@@H]1CN(CC2=CN=CC=C2)CCN1C[C@@H](O)C[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]1[C@H](O)CC2=CC=CC=C12

Pharmacology

Indication

Indinavir is an antiretroviral drug for the treatment of HIV infection.

Associated Conditions
Pharmacodynamics

Indinavir 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. Indinavir 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

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

TargetActionsOrganism
AHuman immunodeficiency virus type 1 protease
inhibitor
Human immunodeficiency virus 1
Absorption

Rapidly absorbed

Volume of distribution
Not Available
Protein binding

60%

Metabolism

Hepatic. Seven metabolites have been identified, one glucuronide conjugate and six oxidative metabolites. In vitro studies indicate that cytochrome P-450 3A4 (CYP3A4) is the major enzyme responsible for formation of the oxidative metabolites.

Route of elimination

Less than 20% of indinavir is excreted unchanged in the urine.

Half life

1.8 (± 0.4) hours

Clearance
Not Available
Toxicity

Symptoms of overdose include myocardial infarction and angina pectoris.

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

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Indinavir can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Indinavir can be decreased when combined with (S)-Warfarin.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Indinavir.
3,5-diiodothyropropionic acidThe metabolism of Indinavir can be decreased when combined with 3,5-diiodothyropropionic acid.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Indinavir.
5-androstenedioneThe metabolism of Indinavir can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Indinavir can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of Indinavir can be decreased when combined with 6-O-benzylguanine.
AbacavirThe metabolism of Abacavir can be decreased when combined with Indinavir.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Indinavir.
Food Interactions
  • Avoid excessive or chronic alcohol use.
  • Avoid taking with grapefruit juice
  • Take on empty stomach: 1 hour before or 2 hours after meals.
  • Take with a full glass of water.

References

Synthesis Reference
US5413999
General References
Not Available
External Links
Human Metabolome Database
HMDB0014369
KEGG Compound
C07051
PubChem Compound
5362440
PubChem Substance
46506442
ChemSpider
4515036
BindingDB
517
ChEBI
44032
ChEMBL
CHEMBL115
Therapeutic Targets Database
DAP000168
PharmGKB
PA449977
HET
MK1
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Indinavir
ATC Codes
J05AE02 — Indinavir
AHFS Codes
  • 08:18.08.08 — HIV Protease Inhibitors
PDB Entries
1c6y / 1hsg / 1hsh / 1k6c / 1sdt / 1sdu / 1sdv / 1sgu / 2avo / 2avs
show 5 more
FDA label
Download (671 KB)
MSDS
Download (57 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Pregnancy1
1CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentCardiovascular Disease (CVD) / High Blood Pressure (Hypertension) / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections7
1, 2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
1, 2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis Infection1
2CompletedTreatmentClassical Kaposi's Sarcoma1
2CompletedTreatmentEwing's Sarcoma (ES) / Rhabdomyosarcomas1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections21
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Infection, Mycobacterium Avium-Intracellulare1
2CompletedTreatmentSarcomas1
2SuspendedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections3
2Unknown StatusTreatmentMalignancies1
2WithdrawnTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections12
3Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4CompletedDiagnosticCardiovascular Disease (CVD) / HIV-Associated Lipodystrophy Syndrome1
4CompletedTreatmentHealthy Volunteers / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentHemophilia A / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections3
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections24
Not AvailableTerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections3
Not AvailableWithdrawnTreatmentHuman Immunodeficiency Virus (HIV) Infections1

Pharmacoeconomics

Manufacturers
  • Merck sharp and dohme corp
Packagers
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Dispensing Solutions
  • H.J. Harkins Co. Inc.
  • Merck & Co.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nucare Pharmaceuticals Inc.
  • Remedy Repack
  • Stat Rx Usa
Dosage forms
FormRouteStrength
CapsuleOral100 mg/1
CapsuleOral200 mg
CapsuleOral200 mg/1
CapsuleOral300 mg
CapsuleOral333 mg/1
CapsuleOral400 mg/1
CapsuleOral400 mg
Prices
Unit descriptionCostUnit
Crixivan 360 200 mg capsule Bottle570.02USD bottle
Crixivan 400 mg capsule2.86USD each
Crixivan 333 mg capsule2.54USD each
Crixivan 200 mg capsule1.52USD each
Crixivan 100 mg capsule0.76USD each
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5413999No1995-05-092012-05-09Us
CA2081970No1997-07-082012-11-02Canada
US6689761No2001-02-102021-02-10Us
US6645961No1998-03-042018-03-04Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)167.5-168 °CNot Available
water solubility0.015 mg/mlNot Available
logP2.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0482 mg/mLALOGPS
logP3.26ALOGPS
logP2.81ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)13.19ChemAxon
pKa (Strongest Basic)7.37ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area118.03 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity175.89 m3·mol-1ChemAxon
Polarizability68.63 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.821
Blood Brain Barrier-0.9923
Caco-2 permeable-0.8183
P-glycoprotein substrateSubstrate0.8899
P-glycoprotein inhibitor IInhibitor0.7987
P-glycoprotein inhibitor IINon-inhibitor0.5819
Renal organic cation transporterNon-inhibitor0.8501
CYP450 2C9 substrateNon-substrate0.7816
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.7831
CYP450 1A2 substrateNon-inhibitor0.9057
CYP450 2C9 inhibitorNon-inhibitor0.6278
CYP450 2D6 inhibitorNon-inhibitor0.7476
CYP450 2C19 inhibitorNon-inhibitor0.6264
CYP450 3A4 inhibitorInhibitor0.6525
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7808
Ames testNon AMES toxic0.8629
CarcinogenicityNon-carcinogens0.887
BiodegradationNot ready biodegradable0.9951
Rat acute toxicity2.1844 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9557
hERG inhibition (predictor II)Inhibitor0.7265
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
Indanes / Piperazine carboxamides / Aralkylamines / N-alkylpiperazines / Benzene and substituted derivatives / N-acyl amines / Pyridines and derivatives / Heteroaromatic compounds / Secondary alcohols / Trialkylamines
show 7 more
Substituents
Alpha-amino acid amide / Indane / Piperazine-2-carboxamide / N-alkylpiperazine / Aralkylamine / Monocyclic benzene moiety / 1,4-diazinane / Fatty amide / N-acyl-amine / Piperazine
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
dicarboxylic acid diamide, N-(2-hydroxyethyl)piperazine, piperazinecarboxamide (CHEBI:44032)

Targets

Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Aspartic-type endopeptidase activity
Specific Function
Not Available
Gene Name
pol
Uniprot ID
Q72874
Uniprot Name
Pol polyprotein
Molecular Weight
10778.7 Da
References
  1. 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]
  2. 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]
  3. Hoetelmans RM, Meenhorst PL, Mulder JW, Burger DM, Koks CH, Beijnen JH: Clinical pharmacology of HIV protease inhibitors: focus on saquinavir, indinavir, and ritonavir. Pharm World Sci. 1997 Aug;19(4):159-75. [PubMed:9297727]
  4. Stein DS, Fish DG, Bilello JA, Preston SL, Martineau GL, Drusano GL: A 24-week open-label phase I/II evaluation of the HIV protease inhibitor MK-639 (indinavir). AIDS. 1996 May;10(5):485-92. [PubMed:8724039]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Human
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. Ekins S, Bravi G, Wikel JH, Wrighton SA: Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33. [PubMed:10490933]
  4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  5. Flockhart Table - Indiana University [Link]
Kind
Protein
Organism
Human
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. 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. [PubMed:16433896]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  4. Flockhart Table - Indiana University [Link]
Kind
Protein
Organism
Human
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
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. 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. [PubMed:16433896]
  4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  5. Flockhart Table - Indiana University [Link]
Details
4. Cytochrome P450 2D6
Kind
Protein
Organism
Human
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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. Yong WP, Ramirez J, Innocenti F, Ratain MJ: Effects of ketoconazole on glucuronidation by UDP-glucuronosyltransferase enzymes. Clin Cancer Res. 2005 Sep 15;11(18):6699-704. doi: 10.1158/1078-0432.CCR-05-0703. [PubMed:16166450]

Transporters

Kind
Protein
Organism
Human
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. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. [PubMed:11602674]
  4. Yamazaki M, Neway WE, Ohe T, Chen I, Rowe JF, Hochman JH, Chiba M, Lin JH: In vitro substrate identification studies for p-glycoprotein-mediated transport: species difference and predictability of in vivo results. J Pharmacol Exp Ther. 2001 Mar;296(3):723-35. [PubMed:11181899]
  5. 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]
  6. Hochman JH, Chiba M, Nishime J, Yamazaki M, Lin JH: Influence of P-glycoprotein on the transport and metabolism of indinavir in Caco-2 cells expressing cytochrome P-450 3A4. J Pharmacol Exp Ther. 2000 Jan;292(1):310-8. [PubMed:10604964]
Kind
Protein
Organism
Human
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Olson DP, Scadden DT, D'Aquila RT, De Pasquale MP: The protease inhibitor ritonavir inhibits the functional activity of the multidrug resistance related-protein 1 (MRP-1). AIDS. 2002 Sep 6;16(13):1743-7. [PubMed:12218384]
Kind
Protein
Organism
Human
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]
Kind
Protein
Organism
Human
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Huisman MT, Smit JW, Crommentuyn KM, Zelcer N, Wiltshire HR, Beijnen JH, Schinkel AH: Multidrug resistance protein 2 (MRP2) transports HIV protease inhibitors, and transport can be enhanced by other drugs. AIDS. 2002 Nov 22;16(17):2295-301. [PubMed:12441801]
Kind
Protein
Organism
Human
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. Annaert P, Ye ZW, Stieger B, Augustijns P: Interaction of HIV protease inhibitors with OATP1B1, 1B3, and 2B1. Xenobiotica. 2010 Mar;40(3):163-76. doi: 10.3109/00498250903509375. [PubMed:20102298]
Kind
Protein
Organism
Human
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 November 14, 2018 12:39