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Identification
- Summary
Lopinavir is an HIV-1 protease inhibitor used in combination with ritonavir to treat human immunodeficiency virus (HIV) infection.
- Brand Names
- Kaletra
- Generic Name
- Lopinavir
- DrugBank Accession Number
- DB01601
- Background
Lopinavir is an antiretroviral protease inhibitor used in combination with other antiretrovirals in the treatment of HIV-1 infection.7 Lopinavir is marketed and administered exclusively in combination with ritonavir - this combination, first marketed by Abbott under the brand name Kaletra in 2000, is necessary due to lopinavir's poor oral bioavailability and extensive biotransformation. Ritonavir is a potent inhibitor of the enzymes responsible for lopinavir metabolism, and its co-administration "boosts" lopinavir exposure and improves antiviral activity.7 Like many other protease inhibitors (e.g. saquinavir, nelfinavir), lopinavir is a peptidomimetic molecule - it contains a hydroxyethylene scaffold that mimics the peptide linkage typically targeted by the HIV-1 protease enzyme but which itself cannot be cleaved, thus preventing the activity of the HIV-1 protease.5
Lopinavir was previously under investigation in combination with ritonavir for the treatment of COVID-19 caused by SARS-CoV-2.8
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Lopinavir (DB01601)
- Weight
- Average: 628.8008
Monoisotopic: 628.362470666 - Chemical Formula
- C37H48N4O5
- Synonyms
- Lopinavir
- External IDs
- A-157378-0
- A-157378.0
- ABT-378
Pharmacology
- Indication
The combination product lopinavir/ritonavir, marketed under the brand name Kaletra, is indicated in combination with other antiretrovirals for the treatment of HIV-1 infection in adults and pediatric patients ≥14 days old.7
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Hiv-1 infection Combination Product in combination with: Ritonavir (DB00503) •••••••••••• ••••••••• •••••• - Contraindications & Blackbox Warnings
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Lopinavir inhibits the activity of an enzyme critical for the HIV viral lifecycle.7 It has a moderate duration of action necessitating once or twice daily dosing.7 Lopinavir, like other protease inhibitors, has a propensity for participating in drug interactions - use caution when administering lopinavir to patients maintained on other pharmaceutical agents as pharmacodynamic and pharmacokinetic interactions are common. Fatal hepatotoxicity and pancreatitis have been noted in patients undergoing therapy with lopinavir and patients with an increased baseline risk of these events should be monitored closely throughout therapy.7
- Mechanism of action
The HIV lifecycle is comprised of 3 distinct stages: assembly, involving creation and packaging of essential viral components; budding, wherein the viral particle crosses the host cell plasma membrane and forms a lipid envelope; and maturation, wherein the viral particle alters its structure and becomes infectious.2 At the center of this lifecycle is the Gag polyprotein which, along with the products of its proteolysis, coordinate these stages and function as the major structural proteins of the virus. The HIV-1 protease enzyme, a dimeric aspartic protease, is the enzyme responsible for cleaving the Gag polyprotein and thus plays a critical role in many aspects of the HIV viral lifecycle.2
Lopinavir is an inhibitor of the HIV-1 protease enzyme.7 Its design is based on the "peptidomimetic" principle, wherein the molecule contains a hydroxyethylene scaffold which mimics the normal peptide linkage (cleaved by HIV protease) but which itself cannot be cleaved.5 By preventing HIV-1 protease activity, and thus the proteolysis of the Gag polyprotein, lopinavir results in the production of immature, non-infectious viral particles.
Target Actions Organism APol polyprotein inhibitorHuman immunodeficiency virus 1 - Absorption
When administered alone, lopinavir has exceptionally low oral bioavailability (~25%) - for this reason, it is exclusively co-administered with ritonavir, which dramatically improves bioavailability, hinders drug metabolism, and allows for the attainment of therapeutic lopinavir concentrations.3,4 Following oral administration of lopinavir/ritonavir, maximal plasma concentrations are achieved at approximately 4.4 hours (Tmax), and the Cmax and AUCtau are 9.8 ± 3.7 - 11.8 ± 3.7 µg/mL and 92.6 ± 36.7 - 154.1 ± 61.4 μg•h/mL, respectively.7
Relative to administration in the fasted state, administration with a meal increases the AUC of the tablet formulation slightly (~19%) but dramatically increases the AUC of the oral solution formulation (~130%).7
- Volume of distribution
The volume of distribution of lopinavir following oral administration is approximately 16.9 L.7
- Protein binding
Lopinavir is >98% protein-bound in plasma.7 It binds to both alpha-1-acid glycoprotein and albumin, but exhibits a greater affinity for alpha-1-acid glycoprotein.10
- Metabolism
Lopinavir undergoes extensive oxidative metabolism, almost exclusively via hepatic CYP3A isozymes.10 Co-administration with ritonavir, a potent inhibitor of CYP3A enzymes, helps to stave off lopinavir's biotransformation and increase plasma levels of active antiviral drug. Twelve metabolites have been identified in vitro, with the C-4 oxidation products M1, M3, and M4 being the predominant metabolites found in plasma.6 The structures of these primary metabolites have been identified, but precise structural information regarding the remaining minor metabolites has not been elucidated.
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- Route of elimination
Lopinavir is primarily eliminated in the feces. Following oral administration, approximately 10.4 ± 2.3% of the administered dose is excreted in the urine and 82.6 ± 2.5% is excreted in the feces.7 Unchanged parent drug accounted for 2.2% and 19.8% of the administered dose in urine and feces, respectively.10
- Half-life
The elimination half-life of lopinavir is 6.9 ± 2.2 hours.7
- Clearance
The estimated apparent clearance following oral administration is approximately 6-7 L/h.3,10
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
As lopinavir is only available in combination with ritonavir, experience with acute lopinavir overdose in isolation is limited. The risk related to overdose appears more pronounced in pediatric patients. One case report detailed a fatal cardiogenic shock in a 2.1kg infant following an approximately 10-fold overdose of Kaletra oral solution, while other reported reactions to overdose in infants include complete AV block, cardiomyopathy, lactic acidosis, and acute renal failure. The oral Kaletra solution is highly concentrated, posing a greater risk of overdose, and contains approximately 42% (v/v) ethanol, further increasing risk in children and infants.7
There is no antidote for lopinavir overdose. Treatment of overdose should consist largely of supportive measures and close observation of vital signs and clinical status of the affected patient. Consideration should be given to the removal of unabsorbed drug using gastric lavage or activated charcoal, if clinically indicated. Dialysis is unlikely to be of benefit as lopinavir is highly protein-bound, but may help to remove ethanol and propylene glycol from the circulation in the case of overdose with Kaletra oral solution.7
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The metabolism of 1,2-Benzodiazepine can be decreased when combined with Lopinavir. Abacavir The serum concentration of Abacavir can be decreased when it is combined with Lopinavir. Abametapir The serum concentration of Lopinavir can be increased when it is combined with Abametapir. Abatacept The serum concentration of Abatacept can be increased when it is combined with Lopinavir. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Lopinavir. - Food Interactions
- Avoid St. John's Wort. Induction of CYP3A by co-administration with St. John's Wort may result in reduced drug plasma concentrations and therapeutic failure.
- Take with food. The oral solution formulation must be taken with food, but the tablet formulation may be taken with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Aluviran / Koletra
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image ALUVIA Lopinavir (100 mg) + Ritonavir (25 mg) Tablet, film coated Oral Abbott Indonesia 2015-11-30 2025-03-06 Indonesia 
ALUVIA Lopinavir (200 mg) + Ritonavir (50 mg) Tablet, film coated Oral Abbott Indonesia 2017-06-05 2022-06-05 Indonesia ALUVIA (100 MG/25 MG) Lopinavir (100 MG) + Ritonavir (25 MG) Tablet, film coated Oral บริษัท ซิลลิค ฟาร์มา จำกัด 2018-05-11 Not applicable Thailand 
DUOVIHR®TABLETA RECUBIERTA Lopinavir (200 mg) + Ritonavir (50 mg) Tablet, coated Oral NUTRI MACK S.A.S. 2018-06-22 Not applicable Colombia 
Kaletra Lopinavir (200 mg/1) + Ritonavir (50 mg/1) Tablet, film coated Oral HHS/Program Support Center/Supply Service Center 2010-06-18 Not applicable US 
- Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Kaletra Lopinavir (200 mg/1) + Ritonavir (50 mg/1) Tablet Oral Remedy Repack 2010-09-27 2013-05-16 US
Categories
- ATC Codes
- J05AR10 — Lopinavir and ritonavir
- Drug Categories
- Anti-HIV Agents
- Anti-Infective Agents
- Anti-Retroviral Agents
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Antivirals used in combination for the treatment of HIV infections
- BSEP/ABCB11 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2B6 Inhibitors (weak)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (weak)
- Cytochrome P-450 CYP2C9 Inducers
- Cytochrome P-450 CYP2C9 Inducers (strength unknown)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (weak)
- Cytochrome P-450 CYP2D6 Substrates
- 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 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Direct Acting Antivirals
- Enzyme Inhibitors
- Experimental Unapproved Treatments for COVID-19
- HIV Protease Inhibitors
- Hyperglycemia-Associated Agents
- Nephrotoxic agents
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- Organic Anion Transporting Polypeptide 1B1 Inhibitors
- P-glycoprotein inducers
- P-glycoprotein inhibitors
- Potential QTc-Prolonging Agents
- Protease Inhibitors
- Pyrimidinones
- QTc Prolonging Agents
- Viral Protease Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as valine and derivatives. These are compounds containing valine or a derivative thereof resulting from reaction of valine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Valine and derivatives
- Alternative Parents
- Amphetamines and derivatives / m-Xylenes / Phenol ethers / Phenoxy compounds / Alkyl aryl ethers / Pyrimidones / Diazinanes / N-acyl amines / Secondary carboxylic acid amides / Ureas show 7 more
- Substituents
- 1,3-diazinane / Alcohol / Alkyl aryl ether / Amphetamine or derivatives / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Carbonic acid derivative / Carbonyl group / Carboxamide group show 23 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- dicarboxylic acid diamide, amphetamines (CHEBI:31781)
- Affected organisms
- Human Immunodeficiency Virus
- SARS-CoV-2
Chemical Identifiers
- UNII
- 2494G1JF75
- CAS number
- 192725-17-0
- InChI Key
- KJHKTHWMRKYKJE-SUGCFTRWSA-N
- InChI
- InChI=1S/C37H48N4O5/c1-25(2)34(41-20-12-19-38-37(41)45)36(44)39-30(21-28-15-7-5-8-16-28)23-32(42)31(22-29-17-9-6-10-18-29)40-33(43)24-46-35-26(3)13-11-14-27(35)4/h5-11,13-18,25,30-32,34,42H,12,19-24H2,1-4H3,(H,38,45)(H,39,44)(H,40,43)/t30-,31-,32-,34-/m0/s1
- IUPAC Name
- (2S)-N-[(2S,4S,5S)-5-[2-(2,6-dimethylphenoxy)acetamido]-4-hydroxy-1,6-diphenylhexan-2-yl]-3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanamide
- SMILES
- CC(C)[C@H](N1CCCNC1=O)C(=O)N[C@H](C[C@H](O)[C@H](CC1=CC=CC=C1)NC(=O)COC1=C(C)C=CC=C1C)CC1=CC=CC=C1
References
- Synthesis Reference
- US5914332
- General References
- Li F, Lu J, Ma X: CYP3A4-mediated lopinavir bioactivation and its inhibition by ritonavir. Drug Metab Dispos. 2012 Jan;40(1):18-24. doi: 10.1124/dmd.111.041400. Epub 2011 Sep 27. [Article]
- Sundquist WI, Krausslich HG: HIV-1 assembly, budding, and maturation. Cold Spring Harb Perspect Med. 2012 Jul;2(7):a006924. doi: 10.1101/cshperspect.a006924. [Article]
- Niu WJ, Sun T, Liu L, Liu XQ, Zhang RF, Yin L, Wang JR, Jia XF, Lu HZ, Zhong MK, Jiao Z, Zhang LJ: Population pharmacokinetics and dosing regimen optimisation of lopinavir in Chinese adults infected with HIV. Basic Clin Pharmacol Toxicol. 2019 Apr;124(4):456-465. doi: 10.1111/bcpt.13154. Epub 2018 Nov 23. [Article]
- Sham HL, Kempf DJ, Molla A, Marsh KC, Kumar GN, Chen CM, Kati W, Stewart K, Lal R, Hsu A, Betebenner D, Korneyeva M, Vasavanonda S, McDonald E, Saldivar A, Wideburg N, Chen X, Niu P, Park C, Jayanti V, Grabowski B, Granneman GR, Sun E, Japour AJ, Leonard JM, Plattner JJ, Norbeck DW: ABT-378, a highly potent inhibitor of the human immunodeficiency virus protease. Antimicrob Agents Chemother. 1998 Dec;42(12):3218-24. [Article]
- De Clercq E: Anti-HIV drugs: 25 compounds approved within 25 years after the discovery of HIV. Int J Antimicrob Agents. 2009 Apr;33(4):307-20. doi: 10.1016/j.ijantimicag.2008.10.010. Epub 2008 Dec 23. [Article]
- Kumar GN, Jayanti V, Lee RD, Whittern DN, Uchic J, Thomas S, Johnson P, Grabowski B, Sham H, Betebenner D, Kempf DJ, Denissen JF: In vitro metabolism of the HIV-1 protease inhibitor ABT-378: species comparison and metabolite identification. Drug Metab Dispos. 1999 Jan;27(1):86-91. [Article]
- FDA Approved Drug Products: Kaletra (lopinavir/ritonavir) for oral use [Link]
- Nature Biotechnology: Coronavirus puts drug repurposing on the fast track [Link]
- CaymanChem: Lopinavir MSDS [Link]
- Health Canada Product Monograph: Kaletra (lopinavir/ritonavir) for oral use [Link]
- External Links
- Human Metabolome Database
- HMDB0015539
- KEGG Drug
- D01425
- KEGG Compound
- C12871
- PubChem Compound
- 92727
- PubChem Substance
- 46508588
- ChemSpider
- 83706
- BindingDB
- 50180655
- 195088
- ChEBI
- 31781
- ChEMBL
- CHEMBL729
- ZINC
- ZINC000003951740
- Therapeutic Targets Database
- DAP000708
- PharmGKB
- PA450264
- PDBe Ligand
- AB1
- RxList
- RxList Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Lopinavir
- PDB Entries
- 1mui / 1rv7 / 2o4s / 2q5k / 2qhc / 2rkf / 2rkg / 2z54 / 3ogq / 4l1a … show 5 more
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
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Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule, liquid filled Oral Tablet Oral Tablet, film coated Oral Syrup Oral 80 mg Tablet, film coated Oral 100 mg Capsule Oral Capsule, coated Oral Granule Oral Solution Oral Tablet, coated Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6703403 Yes 2004-03-09 2016-12-26 US US6037157 Yes 2000-03-14 2016-12-26 US US6232333 Yes 2001-05-15 2018-05-07 US US7432294 Yes 2008-10-07 2020-11-22 US US7141593 Yes 2006-11-28 2020-11-22 US US5914332 Yes 1999-06-22 2016-06-13 US US6284767 Yes 2001-09-04 2016-08-15 US US7364752 Yes 2008-04-29 2021-05-10 US US8309613 Yes 2012-11-13 2025-06-24 US US8377952 Yes 2013-02-19 2028-04-22 US US8691878 Yes 2014-04-08 2025-02-25 US US8025899 Yes 2011-09-27 2028-06-14 US US7148359 Yes 2006-12-12 2020-01-19 US US8470347 Yes 2013-06-25 2027-03-17 US US8268349 Yes 2012-09-18 2025-02-25 US US8399015 Yes 2013-03-19 2025-02-25 US US6458818 Yes 2002-10-01 2018-05-07 US US6521651 Yes 2003-02-18 2018-05-07 US US6911214 Yes 2005-06-28 2022-05-28 US US8501219 No 2013-08-06 2021-11-28 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Practically insoluble Health Canada Monograph - Predicted Properties
Property Value Source Water Solubility 0.00192 mg/mL ALOGPS logP 3.91 ALOGPS logP 4.69 Chemaxon logS -5.5 ALOGPS pKa (Strongest Acidic) 13.39 Chemaxon pKa (Strongest Basic) -1.5 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 120 Å2 Chemaxon Rotatable Bond Count 15 Chemaxon Refractivity 179.36 m3·mol-1 Chemaxon Polarizability 68.78 Å3 Chemaxon Number of Rings 4 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 - 0.6593 Blood Brain Barrier - 0.9916 Caco-2 permeable + 0.8856 P-glycoprotein substrate Substrate 0.8755 P-glycoprotein inhibitor I Inhibitor 0.7355 P-glycoprotein inhibitor II Inhibitor 0.5277 Renal organic cation transporter Non-inhibitor 0.8578 CYP450 2C9 substrate Non-substrate 0.7508 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Substrate 0.6732 CYP450 1A2 substrate Non-inhibitor 0.8935 CYP450 2C9 inhibitor Non-inhibitor 0.7326 CYP450 2D6 inhibitor Non-inhibitor 0.9438 CYP450 2C19 inhibitor Non-inhibitor 0.7983 CYP450 3A4 inhibitor Non-inhibitor 0.6469 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9054 Ames test Non AMES toxic 0.8049 Carcinogenicity Non-carcinogens 0.7865 Biodegradation Not ready biodegradable 0.9182 Rat acute toxicity 2.2503 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8605 hERG inhibition (predictor II) Inhibitor 0.8475
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 265.7032133 predictedDarkChem Lite v0.1.0 [M-H]- 266.6366133 predictedDarkChem Lite v0.1.0 [M-H]- 246.51648 predictedDeepCCS 1.0 (2019) [M+H]+ 265.0788133 predictedDarkChem Lite v0.1.0 [M+H]+ 265.1285133 predictedDarkChem Lite v0.1.0 [M+H]+ 248.34137 predictedDeepCCS 1.0 (2019) [M+Na]+ 265.4873133 predictedDarkChem Lite v0.1.0 [M+Na]+ 253.94719 predictedDeepCCS 1.0 (2019)
Targets
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- 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
- Garriga C, Perez-Elias MJ, Delgado R, Ruiz L, Najera R, Pumarola T, Alonso-Socas Mdel M, Garcia-Bujalance S, Menendez-Arias L: Mutational patterns and correlated amino acid substitutions in the HIV-1 protease after virological failure to nelfinavir- and lopinavir/ritonavir-based treatments. J Med Virol. 2007 Nov;79(11):1617-28. [Article]
- Reddy GS, Ali A, Nalam MN, Anjum SG, Cao H, Nathans RS, Schiffer CA, Rana TM: Design and synthesis of HIV-1 protease inhibitors incorporating oxazolidinones as P2/P2' ligands in pseudosymmetric dipeptide isosteres. J Med Chem. 2007 Sep 6;50(18):4316-28. Epub 2007 Aug 16. [Article]
- Wittayanarakul K, Hannongbua S, Feig M: Accurate prediction of protonation state as a prerequisite for reliable MM-PB(GB)SA binding free energy calculations of HIV-1 protease inhibitors. J Comput Chem. 2008 Apr 15;29(5):673-85. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Authors unspecified: Lopinavir/ritonavir: a protease inhibitor combination. Med Lett Drugs Ther. 2001 Jan 8;43(1095):1-2. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Yeh RF, Gaver VE, Patterson KB, Rezk NL, Baxter-Meheux F, Blake MJ, Eron JJ Jr, Klein CE, Rublein JC, Kashuba AD: Lopinavir/ritonavir induces the hepatic activity of cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP1A2 but inhibits the hepatic and intestinal activity of CYP3A as measured by a phenotyping drug cocktail in healthy volunteers. J Acquir Immune Defic Syndr. 2006 May;42(1):52-60. doi: 10.1097/01.qai.0000219774.20174.64. [Article]
- Weemhoff JL, von Moltke LL, Richert C, Hesse LM, Harmatz JS, Greenblatt DJ: Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir. J Pharm Pharmacol. 2003 Mar;55(3):381-6. doi: 10.1211/002235702739. [Article]
- Sham HL, Betebenner DA, Herrin T, Kumar G, Saldivar A, Vasavanonda S, Molla A, Kempf DJ, Plattner JJ, Norbeck DW: Synthesis and antiviral activities of the major metabolites of the HIV protease inhibitor ABT-378 (Lopinavir). Bioorg Med Chem Lett. 2001 Jun 4;11(11):1351-3. [Article]
- Li F, Lu J, Ma X: CYP3A4-mediated lopinavir bioactivation and its inhibition by ritonavir. Drug Metab Dispos. 2012 Jan;40(1):18-24. doi: 10.1124/dmd.111.041400. Epub 2011 Sep 27. [Article]
- Drug Interactions & Labeling - FDA [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- Anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Weemhoff JL, von Moltke LL, Richert C, Hesse LM, Harmatz JS, Greenblatt DJ: Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir. J Pharm Pharmacol. 2003 Mar;55(3):381-6. doi: 10.1211/002235702739. [Article]
- Li F, Lu J, Ma X: CYP3A4-mediated lopinavir bioactivation and its inhibition by ritonavir. Drug Metab Dispos. 2012 Jan;40(1):18-24. doi: 10.1124/dmd.111.041400. Epub 2011 Sep 27. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- Aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 Da
References
- Li F, Lu J, Ma X: CYP3A4-mediated lopinavir bioactivation and its inhibition by ritonavir. Drug Metab Dispos. 2012 Jan;40(1):18-24. doi: 10.1124/dmd.111.041400. Epub 2011 Sep 27. [Article]
- Weemhoff JL, von Moltke LL, Richert C, Hesse LM, Harmatz JS, Greenblatt DJ: Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir. J Pharm Pharmacol. 2003 Mar;55(3):381-6. doi: 10.1211/002235702739. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). 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 imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
- Specific Function
- (r)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
- Specific Function
- Anandamide 11,12 epoxidase activity
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Weemhoff JL, von Moltke LL, Richert C, Hesse LM, Harmatz JS, Greenblatt DJ: Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir. J Pharm Pharmacol. 2003 Mar;55(3):381-6. doi: 10.1211/002235702739. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- InhibitorInducer
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
- Specific Function
- (r)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Weemhoff JL, von Moltke LL, Richert C, Hesse LM, Harmatz JS, Greenblatt DJ: Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir. J Pharm Pharmacol. 2003 Mar;55(3):381-6. doi: 10.1211/002235702739. [Article]
- Hughes CA, Freitas A, Miedzinski LJ: Interaction between lopinavir/ritonavir and warfarin. CMAJ. 2007 Aug 14;177(4):357-9. doi: 10.1503/cmaj.061284. [Article]
- Lim ML, Min SS, Eron JJ, Bertz RJ, Robinson M, Gaedigk A, Kashuba AD: Coadministration of lopinavir/ritonavir and phenytoin results in two-way drug interaction through cytochrome P-450 induction. J Acquir Immune Defic Syndr. 2004 Aug 15;36(5):1034-40. [Article]
- Kaletra FDA label [File]
- Cytochrome P450 Enzymes and Transporters Induced by Anti-Human Immunodeficiency Virus Protease Inhibitors in Human Hepatocytes: Implications for Predicting Clinical Drug Interactions [File]
- Kaletra EPAR [File]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
Components:
| Name | UniProt ID |
|---|---|
| Cytochrome P450 3A4 | P08684 |
| Cytochrome P450 3A43 | Q9HB55 |
| Cytochrome P450 3A5 | P20815 |
| Cytochrome P450 3A7 | P24462 |
References
- Weemhoff JL, von Moltke LL, Richert C, Hesse LM, Harmatz JS, Greenblatt DJ: Apparent mechanism-based inhibition of human CYP3A in-vitro by lopinavir. J Pharm Pharmacol. 2003 Mar;55(3):381-6. doi: 10.1211/002235702739. [Article]
- FDA Approved Drug Products: Kaletra (lopinavir/ritonavir) for oral use [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Functions as a 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 the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction
- Specific Function
- Not Available
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23539.43 Da
References
- Health Canada Product Monograph: Kaletra (lopinavir/ritonavir) for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- Antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Health Canada Product Monograph: Kaletra (lopinavir/ritonavir) for oral use [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- InhibitorInducer
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- Abc-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463)
- Specific Function
- Bile acid transmembrane transporter activity
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 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. [Article]
- FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
- FDA Approved Drug Products: Kaletra (lopinavir/ritonavir) for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10779507, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) (PubMed:10779507, PubMed:11159893, PubMed:12568656, PubMed:15159445, PubMed:17412826, PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Involved in the clearance of bile acids and organic anions from the liver (PubMed:22232210). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:15159445). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748)
- Specific Function
- Bile acid transmembrane transporter activity
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:15791618, PubMed:16332456, PubMed:18985798, PubMed:19228692, PubMed:20010382, PubMed:20398791, PubMed:22262466, PubMed:24711118, PubMed:29507376, PubMed:32203132). Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456). Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (PubMed:15901796, PubMed:18245269)
- Specific Function
- Abc-type bile acid transporter activity
- 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. [Article]
Drug created at August 29, 2007 18:45 / Updated at April 01, 2022 19:23