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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyIdentification
- Name
- Saquinavir
- Accession Number
- DB01232 (APRD00623)
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Description
An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases.
- Structure
Structure for Saquinavir (DB01232)
- Synonyms
- Saquinavir
- External IDs
- RO 31-8959/000 / RO-31-8959/000 / SCH-52852
- Product Ingredients
Ingredient UNII CAS InChI Key Saquinavir mesylate UHB9Z3841A 149845-06-7 IRHXGOXEBNJUSN-YOXDLBRISA-N - Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Unlock Additional DataFortovase Capsule, liquid filled 200 mg/1 Oral Genentech, Inc. 1997-11-07 2012-04-18 US 
Fortovase Roche Capsule Oral Hoffmann La Roche 1998-11-26 2007-03-06 Canada 
Invirase Capsule 200 mg Oral Roche Registration Gmb H 1996-10-04 Not applicable EU 
Invirase Tablet 500 mg Oral Hoffmann La Roche 2006-04-10 Not applicable Canada Invirase Tablet, film coated 500 mg/1 Oral Genentech, Inc. 2004-12-17 Not applicable US Invirase Capsule 200 mg/1 Oral Genentech, Inc. 1995-12-06 Not applicable US Invirase Capsule 200 mg/1 Oral REMEDYREPACK INC. 2013-05-01 2013-05-02 US Invirase Tablet, film coated 500 mg/1 Oral State of Florida DOH Central Pharmacy 2009-07-01 Not applicable US Invirase Tablet, film coated 500 mg Oral Roche Registration Gmb H 1996-10-04 Not applicable EU Invirase - Cap 200mg Capsule Oral Hoffmann La Roche 1996-12-31 2018-12-31 Canada Additional Data Available- Application NumberApplication Number
A unique ID assigned by the FDA when a product is submitted for approval by the labeller.
Learn more - Product CodeProduct Code
A governmentally-recognized ID which uniquely identifies the product within its regulatory market.
Learn more
- Categories
- Agents Causing Muscle Toxicity
- Anti-HIV Agents
- Anti-Infective Agents
- Anti-Retroviral Agents
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- BCRP/ABCG2 Inhibitors
- BSEP/ABCB11 Substrates
- Chemically-Induced Disorders
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (moderate)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (weak)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strong)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Inhibitors
- Cytochrome P-450 CYP3A5 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A5 Inhibitors (strong)
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A7 Inhibitors
- Cytochrome P-450 CYP3A7 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A7 Inhibitors (weak)
- Cytochrome P-450 CYP3A7 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Direct Acting Antivirals
- Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- HIV Protease Inhibitors
- Hyperglycemia-Associated Agents
- Isoquinolines
- Moderate Risk QTc-Prolonging Agents
- OATP1B1/SLCO1B1 Inhibitors
- OCT1 inhibitors
- P-glycoprotein inducers
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Protease Inhibitors
- QTc Prolonging Agents
- Quinolines
- UNII
- L3JE09KZ2F
- CAS number
- 127779-20-8
- Weight
- Average: 670.8408
Monoisotopic: 670.38426874 - Chemical Formula
- C38H50N6O5
- InChI Key
- QWAXKHKRTORLEM-UGJKXSETSA-N
- InChI
- InChI=1S/C38H50N6O5/c1-38(2,3)43-37(49)32-20-26-14-7-8-15-27(26)22-44(32)23-33(45)30(19-24-11-5-4-6-12-24)41-36(48)31(21-34(39)46)42-35(47)29-18-17-25-13-9-10-16-28(25)40-29/h4-6,9-13,16-18,26-27,30-33,45H,7-8,14-15,19-23H2,1-3H3,(H2,39,46)(H,41,48)(H,42,47)(H,43,49)/t26-,27+,30-,31-,32-,33+/m0/s1
- IUPAC Name
- (2S)-N-[(2S,3R)-4-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)-decahydroisoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-[(quinolin-2-yl)formamido]butanediamide
- SMILES
- [H][C@@]12CCCC[C@]1([H])CN(C[C@@H](O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(N)=O)NC(=O)C1=NC3=C(C=CC=C3)C=C1)[C@@H](C2)C(=O)NC(C)(C)C
Pharmacology
- Indication
For the treatment of HIV-1 with advanced immunodeficiency together with antiretroviral nucleoside analogues.
- Associated Conditions
- Pharmacodynamics
Saquinavir 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. Saquinavir 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
Saquinavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.
Target Actions Organism AHuman immunodeficiency virus type 1 protease inhibitorHuman immunodeficiency virus 1 - Absorption
Absolute bioavailability averages 4%
- Volume of distribution
- 700 L
- Protein binding
98%
- Metabolism
Hepatic
- Saquinavir M2 di-hydroxylated metabolite
- Saquinavir (2S)-N-[(2S,3R)-4-[(3S,4aS,8aS)-3-[(1-hydroxy-2-methylpropan-2-yl)carbamoyl]-decahydroisoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-[(quinolin-2-yl)formamido]butanediamide
- Saquinavir (2S)-N-[(2S,3R)-4-[(3S,4aR,8aS)-3-(tert-butylcarbamoyl)-6-hydroxy-decahydroisoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-[(quinolin-2-yl)formamido]butanediamide
- Saquinavir (2S)-N-[(2S,3R)-4-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)-7-hydroxy-decahydroisoquinolin-2-yl]-3-hydroxy-1-phenylbutan-2-yl]-2-[(quinolin-2-yl)formamido]butanediamide
- Route of elimination
In vitro studies using human liver microsomes have shown that the metabolism of saquinavir is cytochrome P450 mediated with the specific isoenzyme, CYP3A4, responsible for more than 90% of the hepatic metabolism. Only 1% of saquinavir is excreted in the urine, so the impact of renal impairment on saquinavir elimination should be minimal.
- Half life
- Not Available
- Clearance
- 1.14 L/h/kg [Healthy volunteers receiving IV doses of 6, 36, and 72 mg]
- Toxicity
Probably experience pain in the throat
- Affected organisms
- Human Immunodeficiency Virus
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Unlock Additional Data
Additional Data Available
Adverse Effects
Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.
Learn more Additional Data Available
Contraindications
Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.
Learn more Additional Data Available
Blackbox Warnings
Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.
Learn moreInteractions
- 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.
Drug Interaction Unlock Additional Data(R)-warfarin The serum concentration of (R)-warfarin can be increased when it is combined with Saquinavir. (S)-Warfarin The serum concentration of (S)-Warfarin can be increased when it is combined with Saquinavir. 2,4-thiazolidinedione The therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Saquinavir. 4-hydroxycoumarin The metabolism of 4-hydroxycoumarin can be decreased when combined with Saquinavir. 4-Methoxyamphetamine The metabolism of 4-Methoxyamphetamine can be decreased when combined with Saquinavir. 5-methoxy-N,N-dimethyltryptamine The metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Saquinavir. 9-aminocamptothecin The metabolism of Saquinavir can be decreased when combined with 9-aminocamptothecin. Abatacept The metabolism of Saquinavir can be increased when combined with Abatacept. Abemaciclib The metabolism of Saquinavir can be decreased when combined with Abemaciclib. Abexinostat The risk or severity of QTc prolongation can be increased when Saquinavir is combined with Abexinostat. Additional Data Available- Extended DescriptionExtended Description
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - Severity
- Evidence Level
- ActionAction
An effect category for each drug interaction. Know how this interaction affects the subject drug.
Learn more
- Food Interactions
- Take after a meal.
References
- Synthesis Reference
- US5196438
- General References
- Forestier F, de Renty P, Peytavin G, Dohin E, Farinotti R, Mandelbrot L: Maternal-fetal transfer of saquinavir studied in the ex vivo placental perfusion model. Am J Obstet Gynecol. 2001 Jul;185(1):178-81. [PubMed:11483925]
- External Links
- KEGG Drug
- D00429
- PubChem Compound
- 441243
- PubChem Substance
- 46508726
- ChemSpider
- 390016
- BindingDB
- 519
- RxNav
- 83395
- ChEBI
- 63621
- ChEMBL
- CHEMBL114
- ZINC
- ZINC000003914596
- Therapeutic Targets Database
- DAP000171
- PharmGKB
- PA451305
- PDBe Ligand
- ROC
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Saquinavir
- ATC Codes
- J05AE01 — Saquinavir
- AHFS Codes
- 08:18.08.08 — HIV Protease Inhibitors
- PDB Entries
- 1c6z / 1fb7 / 1hxb / 2nmy / 2nmz / 2nnk / 2nnp / 3cyx / 3d1x / 3d1y … show 17 more
- FDA label
- Download (362 KB)
- MSDS
- Download (15.8 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- A-S Medication Solutions LLC
- F Hoffmann La Roche Ltd.
- F Hoffmann-La Roche Ltd.
- Pharmaceutical Utilization Management Program VA Inc.
- Physicians Total Care Inc.
- R.P. Scherer GmbH and Co. KG
- Dosage forms
Form Route Strength Capsule, liquid filled Oral 200 mg/1 Capsule Oral 200 mg Capsule Oral 200 mg/1 Tablet Oral 500 mg Tablet, film coated Oral 500 mg/1 Tablet, film coated Oral 500 mg Capsule Oral - Prices
Unit description Cost Unit Invirase 500 mg tablet 8.72USD tablet Invirase 200 mg capsule 3.87USD capsule Fortovase 200 mg capsule 1.46USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Unlock Additional DataUS5196438 No 1993-03-23 2010-11-19 US CA2224125 No 2004-09-28 2016-06-04 Canada CA2030433 No 1997-10-21 2010-11-21 Canada US6352717 Yes 2002-03-05 2020-05-16 US US6008228 Yes 1999-12-28 2015-12-06 US Additional Data Available- Filed On
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 349.84 °C Not Available water solubility Insoluble Not Available logP 3.8 Not Available Caco2 permeability -6.26 ADME Research, USCD - Predicted Properties
Property Value Source Water Solubility 0.00247 mg/mL ALOGPS logP 4.04 ALOGPS logP 3.16 ChemAxon logS -5.4 ALOGPS pKa (Strongest Acidic) 13.61 ChemAxon pKa (Strongest Basic) 8.47 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 7 ChemAxon Hydrogen Donor Count 5 ChemAxon Polar Surface Area 166.75 Å2 ChemAxon Rotatable Bond Count 13 ChemAxon Refractivity 186.67 m3·mol-1 ChemAxon Polarizability 73.76 Å3 ChemAxon Number of Rings 5 ChemAxon Bioavailability 0 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.7774 Blood Brain Barrier - 0.9949 Caco-2 permeable - 0.8957 P-glycoprotein substrate Substrate 0.9048 P-glycoprotein inhibitor I Inhibitor 0.8563 P-glycoprotein inhibitor II Inhibitor 0.5195 Renal organic cation transporter Non-inhibitor 0.8612 CYP450 2C9 substrate Non-substrate 0.8593 CYP450 2D6 substrate Substrate 0.8918 CYP450 3A4 substrate Substrate 0.7406 CYP450 1A2 substrate Non-inhibitor 0.8729 CYP450 2C9 inhibitor Non-inhibitor 0.7442 CYP450 2D6 inhibitor Non-inhibitor 0.8536 CYP450 2C19 inhibitor Non-inhibitor 0.7124 CYP450 3A4 inhibitor Inhibitor 0.5219 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9053 Ames test Non AMES toxic 0.8489 Carcinogenicity Non-carcinogens 0.865 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.6007 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9687 hERG inhibition (predictor II) Inhibitor 0.8153
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Taxonomy
- Description
- This compound belongs to the class of organic compounds known as quinoline carboxamides. These are quinolines in which the quinoline ring system is substituted by one or more carboxamide groups.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Quinolines and derivatives
- Sub Class
- Quinoline carboxamides
- Direct Parent
- Quinoline carboxamides
- Alternative Parents
- Phenylbutylamines / Amphetamines and derivatives / Pyridinecarboxylic acids and derivatives / Piperidinecarboxamides / 2-heteroaryl carboxamides / Aralkylamines / Heteroaromatic compounds / Trialkylamines / Secondary carboxylic acid amides / Secondary alcohols show 8 more
- Substituents
- Quinoline-2-carboxamide / Phenylbutylamine / Amphetamine or derivatives / 2-piperidinecarboxamide / Piperidinecarboxamide / Pyridine carboxylic acid or derivatives / 2-heteroaryl carboxamide / Aralkylamine / Monocyclic benzene moiety / Piperidine show 26 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- quinolines, L-asparagine derivative (CHEBI:63621)
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
- 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]
- 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]
- Dandache S, Coburn CA, Oliveira M, Allison TJ, Holloway MK, Wu JJ, Stranix BR, Panchal C, Wainberg MA, Vacca JP: PL-100, a novel HIV-1 protease inhibitor displaying a high genetic barrier to resistance: an in vitro selection study. J Med Virol. 2008 Dec;80(12):2053-63. doi: 10.1002/jmv.21329. [PubMed:19040279]
- Rhee SY, Taylor J, Fessel WJ, Kaufman D, Towner W, Troia P, Ruane P, Hellinger J, Shirvani V, Zolopa A, Shafer RW: HIV-1 protease mutations and protease inhibitor cross-resistance. Antimicrob Agents Chemother. 2010 Oct;54(10):4253-61. doi: 10.1128/AAC.00574-10. Epub 2010 Jul 26. [PubMed:20660676]
- Alcaro S, Artese A, Ceccherini-Silberstein F, Ortuso F, Perno CF, Sing T, Svicher V: Molecular dynamics and free energy studies on the wild-type and mutated HIV-1 protease complexed with four approved drugs: mechanism of binding and drug resistance. J Chem Inf Model. 2009 Jul;49(7):1751-61. doi: 10.1021/ci900012k. [PubMed:19537723]
- Vella S, Lazzarin A, Carosi G, Sinicco A, Armignacco O, Angarano G, Andreoni M, Tambussi G, Chiodera A, Floridia M, Scaccabarozzi S, Facey K, Duncan I, Boudes P, Bragman K: A randomized controlled trial of a protease inhibitor (saquinavir) in combination with zidovudine in previously untreated patients with advanced HIV infection. Antivir Ther. 1996 Aug;1(3):129-40. [PubMed:11322246]
- 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]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- 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]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- 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]
- Frohlich M, Hoffmann MM, Burhenne J, Mikus G, Weiss J, Haefeli WE: Association of the CYP3A5 A6986G (CYP3A5*3) polymorphism with saquinavir pharmacokinetics. Br J Clin Pharmacol. 2004 Oct;58(4):443-4. doi: 10.1111/j.1365-2125.2004.02159.x. [PubMed:15373940]
- Josephson F, Allqvist A, Janabi M, Sayi J, Aklillu E, Jande M, Mahindi M, Burhenne J, Bottiger Y, Gustafsson LL, Haefeli WE, Bertilsson L: CYP3A5 genotype has an impact on the metabolism of the HIV protease inhibitor saquinavir. Clin Pharmacol Ther. 2007 May;81(5):708-12. doi: 10.1038/sj.clpt.6100117. Epub 2007 Feb 28. [PubMed:17329995]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- 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]
- 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]
- Eagling VA, Wiltshire H, Whitcombe IW, Back DJ: CYP3A4-mediated hepatic metabolism of the HIV-1 protease inhibitor saquinavir in vitro. Xenobiotica. 2002 Jan;32(1):1-17. doi: 10.1080/00498250110085845. [PubMed:11824416]
- Schmitt C, Hofmann C, Riek M, Patel A, Zwanziger E: Effect of saquinavir-ritonavir on cytochrome P450 3A4 activity in healthy volunteers using midazolam as a probe. Pharmacotherapy. 2009 Oct;29(10):1175-81. doi: 10.1592/phco.29.10.1175. [PubMed:19792991]
- Flockhart Table of Drug Interactions [Link]
- FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
- 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
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]
- Parikh S, Ouedraogo JB, Goldstein JA, Rosenthal PJ, Kroetz DL: Amodiaquine metabolism is impaired by common polymorphisms in CYP2C8: implications for malaria treatment in Africa. Clin Pharmacol Ther. 2007 Aug;82(2):197-203. doi: 10.1038/sj.clpt.6100122. Epub 2007 Mar 14. [PubMed:17361129]
- 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
- 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]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Holladay JW, Dewey MJ, Michniak BB, Wiltshire H, Halberg DL, Weigl P, Liang Z, Halifax K, Lindup WE, Back DJ: Elevated alpha-1-acid glycoprotein reduces the volume of distribution and systemic clearance of saquinavir. Drug Metab Dispos. 2001 Mar;29(3):299-303. [PubMed:11181499]
- 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
- Holladay JW, Dewey MJ, Michniak BB, Wiltshire H, Halberg DL, Weigl P, Liang Z, Halifax K, Lindup WE, Back DJ: Elevated alpha-1-acid glycoprotein reduces the volume of distribution and systemic clearance of saquinavir. Drug Metab Dispos. 2001 Mar;29(3):299-303. [PubMed:11181499]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitorInducer
- 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
- 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]
- 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]
- 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]
- Kim AE, Dintaman JM, Waddell DS, Silverman JA: Saquinavir, an HIV protease inhibitor, is transported by P-glycoprotein. J Pharmacol Exp Ther. 1998 Sep;286(3):1439-45. [PubMed:9732409]
- Huisman MT, Smit JW, Wiltshire HR, Hoetelmans RM, Beijnen JH, Schinkel AH: P-glycoprotein limits oral availability, brain, and fetal penetration of saquinavir even with high doses of ritonavir. Mol Pharmacol. 2001 Apr;59(4):806-13. [PubMed:11259625]
- Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. [PubMed:12948019]
- Eagling VA, Profit L, Back DJ: Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-1 protease inhibitor saquinavir by grapefruit juice components. Br J Clin Pharmacol. 1999 Oct;48(4):543-52. [PubMed:10583025]
- Collett A, Tanianis-Hughes J, Hallifax D, Warhurst G: Predicting P-glycoprotein effects on oral absorption: correlation of transport in Caco-2 with drug pharmacokinetics in wild-type and mdr1a(-/-) mice in vivo. Pharm Res. 2004 May;21(5):819-26. [PubMed:15180340]
- FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
- 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
- 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]
- Moss DM, Liptrott NJ, Siccardi M, Owen A: Interactions of antiretroviral drugs with the SLC22A1 (OCT1) drug transporter. Front Pharmacol. 2015 Apr 10;6:78. doi: 10.3389/fphar.2015.00078. eCollection 2015. [PubMed:25914645]
- 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
- 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
- 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
- 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]
- Janneh O, Owen A, Chandler B, Hartkoorn RC, Hart CA, Bray PG, Ward SA, Back DJ, Khoo SH: Modulation of the intracellular accumulation of saquinavir in peripheral blood mononuclear cells by inhibitors of MRP1, MRP2, P-gp and BCRP. AIDS. 2005 Dec 2;19(18):2097-102. [PubMed:16284458]
- 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
- 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
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- Williams GC, Liu A, Knipp G, Sinko PJ: Direct evidence that saquinavir is transported by multidrug resistance-associated protein (MRP1) and canalicular multispecific organic anion transporter (MRP2). Antimicrob Agents Chemother. 2002 Nov;46(11):3456-62. [PubMed:12384350]
- Kind
- Protein
- Organism
- Humans
- 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
- Williams GC, Liu A, Knipp G, Sinko PJ: Direct evidence that saquinavir is transported by multidrug resistance-associated protein (MRP1) and canalicular multispecific organic anion transporter (MRP2). Antimicrob Agents Chemother. 2002 Nov;46(11):3456-62. [PubMed:12384350]
- 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]
- Zelcer N, Huisman MT, Reid G, Wielinga P, Breedveld P, Kuil A, Knipscheer P, Schellens JH, Schinkel AH, Borst P: Evidence for two interacting ligand binding sites in human multidrug resistance protein 2 (ATP binding cassette C2). J Biol Chem. 2003 Jun 27;278(26):23538-44. Epub 2003 Apr 17. [PubMed:12702717]
- Honda Y, Ushigome F, Koyabu N, Morimoto S, Shoyama Y, Uchiumi T, Kuwano M, Ohtani H, Sawada Y: Effects of grapefruit juice and orange juice components on P-glycoprotein- and MRP2-mediated drug efflux. Br J Pharmacol. 2004 Dec;143(7):856-64. Epub 2004 Oct 25. [PubMed:15504753]
- 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
- 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
- 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
- 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 May 24, 2020 19:35
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