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Identification
- Summary
Lurbinectedin is a chemotherapeutic DNA alkylating agent used in the treatment of metastatic small-cell lung cancer.
- Brand Names
- Zepzelca
- Generic Name
- Lurbinectedin
- DrugBank Accession Number
- DB12674
- Background
Lurbinectedin is a DNA alkylating agent that has been investigated in the treatment of a variety of cancers, including mesothelioma,4 chronic lymphocytic leukemia (CLL),5 breast cancer,3 and small-cell lung cancer (SCLC).1 It is a derivative of the marine-derived agent ecteinascidin (trabectedin), an anticancer agent found in extracts of the tunicate Ecteinascidia turbinata, with the primary difference being the substitution of the tetrahydroisoquinoline with a tetrahydro β‐carboline that results in increased antitumour activity of lurbinectedin as compared to its predecessor.6
On June 15, 2020, the FDA granted accelerated approval and orphan drug designation to lurbinectedin for the treatment of adult patients with metastatic SCLC who have experienced disease progression despite therapy with platinum-based agents.8 This accelerated approval is based on the rate and duration of therapeutic response observed in ongoing clinical trials and is contingent on the verification of these results in confirmatory trials.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Lurbinectedin (DB12674)
- Weight
- Average: 784.88
Monoisotopic: 784.277814807 - Chemical Formula
- C41H44N4O10S
- Synonyms
- Lurbinectedin
- External IDs
- PM 01183
- PM-01183
- PM01183
- PM1183
- WHO 9397
Pharmacology
- Indication
Lurbinectedin is indicated for the treatment of adult patients with metastatic small-cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.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 Treatment of Metastatic small cell lung cancer •••••••••••• ••••• ••••••• ••••••••••• •• •• ••••• •••••••••••••• •••••••••••• - Contraindications & Blackbox Warnings
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Lurbinectedin exerts its chemotherapeutic activity by covalently binding to DNA, resulting in double-strand DNA breaks and subsequent cell death.1 Lurbinectedin has been associated with myelosuppression, and patients receiving therapy with this agent should be closely monitored for evidence of cytopenias. Prior to beginning therapy, ensure baseline neutrophil counts are >1,500 cells/mm3 and platelet counts are >100,000/mm3.7 The supplementary use of granulocyte colony-stimulating factor (G-CSF) should be considered if the neutrophil count falls below 500 cells/mm3.7 Lurbinectedin has also been associated with hepatotoxicity.7 Monitor liver function tests at baseline and regular intervals throughout therapy, and consider holding, reducing, or permanently discontinuing therapy based on the severity of observed hepatotoxicity.7
- Mechanism of action
Lurbinectedin is a DNA alkylating agent.7 It covalently binds to guanine residues in the DNA minor groove, forming adducts that bend the DNA helix towards the major groove. This process triggers a cascade of events that affect the activity of transcription factors and impairs DNA repair pathways, ultimately leading to double-strand DNA breaks and eventual cell death.7,1 Additional mechanism(s) of action include inhibition of RNA-polymerase-II activity, inactivation of Ewing Sarcoma Oncoprotein (EWS-FL11) via nuclear redistribution, and the inhibition of human monocyte activity and macrophage infiltration into tumor tissue.7,1
Target Actions Organism UDNA adductHumans - Absorption
Following intravenous administration, the Cmax and AUC0-inf were 107 µg/L and 551 µg*h/L, respectively. No accumulation between dosing intervals (every 3 weeks) has been observed.7 No significant differences in absorption were found between special populations (e.g. based on age, sex, ethnicity, etc.), but lurbinectedin has not been studied in the setting of severe renal impairment or moderate/severe hepatic impairment.
- Volume of distribution
The steady-state volume of distribution of lurbinectedin is 504 L.7
- Protein binding
Lurbinectedin is highly protein-bound in plasma (~99%) to both serum albumin and α-1-acid glycoprotein.7
- Metabolism
Lurbinectedin is metabolized primarily by CYP3A4 in vitro, though specific data regarding its biotransformation are lacking.7 An N-desmethylated metabolite has been identified in canine subjects.2
- Route of elimination
Approximately 89% of a given dose is recovered in the feces (<0.2% unchanged) and 6% in the urine (1% unchanged).7
- Half-life
The terminal half-life of lurbinectedin is 51 hours.7
- Clearance
The total plasma clearance of lurbinectedin is approximately 11 L/h.7
- 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
Data regarding overdosage with lurbinectedin are not available. Symptoms of overdose are likely to be consistent with lurbinectedin's adverse effect profile.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 softwareAbametapir The serum concentration of Lurbinectedin can be increased when it is combined with Abametapir. Ambroxol The risk or severity of methemoglobinemia can be increased when Lurbinectedin is combined with Ambroxol. Amiodarone The serum concentration of Lurbinectedin can be increased when it is combined with Amiodarone. Amprenavir The serum concentration of Lurbinectedin can be increased when it is combined with Amprenavir. Apalutamide The serum concentration of Lurbinectedin can be decreased when it is combined with Apalutamide. - Food Interactions
- No interactions found.
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
- Zepsyre
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Zepzelca Powder 4 mg / vial Intravenous Jazz Pharmaceuticals Ireland Limited 2021-12-06 Not applicable Canada 
Zepzelca Injection, powder, lyophilized, for solution .5 mg/1mL Intravenous Jazz Pharmaceuticals, Inc. 2020-06-15 Not applicable US 
Categories
- ATC Codes
- L01XX69 — Lurbinectedin
- Drug Categories
- Alkylating Drugs
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Heterocyclic Compounds, Fused-Ring
- Indole Alkaloids
- Indoles
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- OCT1 inhibitors
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Pyridines
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as harmala alkaloids. These are compounds with a structure based on harmaline, harmine, harmalol, harman or a derivative of those parents. These parents are beta-carbolines, consisting of a pyrimidine fused to the pyrrole moiety of an indole to form a pyrido[3,4-b]indole.
- Kingdom
- Organic compounds
- Super Class
- Alkaloids and derivatives
- Class
- Harmala alkaloids
- Sub Class
- Not Available
- Direct Parent
- Harmala alkaloids
- Alternative Parents
- Beta carbolines / Benzazocines / Tetrahydroisoquinolines / 3-alkylindoles / Alpha amino acids and derivatives / Benzodioxoles / Anisoles / 1-hydroxy-4-unsubstituted benzenoids / Alkyl aryl ethers / N-methylpiperazines show 17 more
- Substituents
- 1,4-diazinane / 1-hydroxy-4-unsubstituted benzenoid / 3-alkylindole / Acetal / Alkanolamine / Alkyl aryl ether / Alpha-amino acid or derivatives / Amine / Amino acid or derivatives / Anisole show 39 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 2CN60TN6ZS
- CAS number
- 497871-47-3
- InChI Key
- YDDMIZRDDREKEP-HWTBNCOESA-N
- InChI
- InChI=1S/C41H44N4O10S/c1-17-11-20-12-25-39(48)45-26-14-52-40(49)41(38-22(9-10-42-41)23-13-21(50-5)7-8-24(23)43-38)15-56-37(31(45)30(44(25)4)27(20)32(47)33(17)51-6)29-28(26)36-35(53-16-54-36)18(2)34(29)55-19(3)46/h7-8,11,13,25-26,30-31,37,39,42-43,47-48H,9-10,12,14-16H2,1-6H3/t25-,26-,30+,31+,37+,39-,41+/m0/s1
- IUPAC Name
- (1R,2R,3R,11S,12S,14R,26R)-5,12-dihydroxy-6,6'-dimethoxy-7,21,30-trimethyl-27-oxo-2',3',4',9'-tetrahydro-17,19,28-trioxa-24-thia-13,30-diazaspiro[heptacyclo[12.9.6.1^{3,11}.0^{2,13}.0^{4,9}.0^{15,23}.0^{16,20}]triacontane-26,1'-pyrido[3,4-b]indole]-4,6,8,15,20,22-hexaen-22-yl acetate
- SMILES
- [H][C@@]12[C@@H]3SC[C@]4(NCCC5=C4NC4=CC=C(OC)C=C54)C(=O)OC[C@H](N1[C@@H](O)[C@@H]1CC4=CC(C)=C(OC)C(O)=C4[C@@]2([H])N1C)C1=C2OCOC2=C(C)C(OC(C)=O)=C31
References
- Synthesis Reference
He W, Zhang Z, Ma D: A Scalable Total Synthesis of the Antitumor Agents Et-743 and Lurbinectedin. Angew Chem Int Ed Engl. 2019 Mar 18;58(12):3972-3975. doi: 10.1002/anie.201900035. Epub 2019 Feb 14.
- General References
- Kauffmann-Guerrero D, Huber RM: Orphan Drugs in Development for the Treatment of Small-Cell Lung Cancer: Emerging Data on Lurbinectedin. Lung Cancer (Auckl). 2020 Mar 2;11:27-31. doi: 10.2147/LCTT.S239223. eCollection 2020. [Article]
- Altares R, Marquez Del Pino FM, Benedit G, Guillen MJ, Cuevas C, Perez de la Cruz MA, Aviles P: Development of a new method for the quantitation of metabolites in the absence of chemically synthetized authentic standards. J Pharm Biomed Anal. 2019 May 30;169:70-74. doi: 10.1016/j.jpba.2019.01.027. Epub 2019 Feb 21. [Article]
- Gourd E: Lurbinectedin for BRCA-mutated advanced breast cancer. Lancet Oncol. 2018 Nov;19(11):e582. doi: 10.1016/S1470-2045(18)30737-X. Epub 2018 Sep 27. [Article]
- Metaxas Y, Fruh M, Eboulet EI, Grosso F, Pless M, Zucali PA, Ceresoli GL, Mark M, Schneider M, Maconi A, Perrino M, Biaggi-Rudolf C, Froesch P, Schmid S, Waibel C, Appenzeller C, Rauch D, von Moos R: Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16). Ann Oncol. 2020 Apr;31(4):495-500. doi: 10.1016/j.annonc.2019.12.009. Epub 2020 Jan 16. [Article]
- Risnik D, Colado A, Podaza E, Almejun MB, Elias EE, Bezares RF, Fernandez-Grecco H, Seija N, Oppezzo P, Borge M, Gamberale R, Giordano M: Immunoregulatory effects of Lurbinectedin in chronic lymphocytic leukemia. Cancer Immunol Immunother. 2020 May;69(5):813-824. doi: 10.1007/s00262-020-02513-y. Epub 2020 Feb 13. [Article]
- Jimenez PC, Wilke DV, Branco PC, Bauermeister A, Rezende-Teixeira P, Gaudencio SP, Costa-Lotufo LV: Enriching cancer pharmacology with drugs of marine origin. Br J Pharmacol. 2020 Jan;177(1):3-27. doi: 10.1111/bph.14876. Epub 2019 Dec 23. [Article]
- FDA Approved Drug Products: Zepzelca (lurbinectedin) for intravenous injection [Link]
- FDA Drug Approvals and Databases: FDA grants accelerated approval to lurbinectedin for metastatic small cell lung cancer [Link]
- External Links
- PubChem Compound
- 57327016
- PubChem Substance
- 347828878
- ChemSpider
- 32701856
- 2374729
- ChEMBL
- CHEMBL4297516
- Wikipedia
- Lurbinectedin
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Recruiting Not Available Extensive-stage Small Cell Lung Cancer (SCLC) 1 somestatus stop reason just information to hide 3 Active Not Recruiting Treatment Small Cell Lung Cancer (SCLC) 2 somestatus stop reason just information to hide 3 Completed Treatment Ovarian Cancer 1 somestatus stop reason just information to hide 3 Completed Treatment Small Cell Lung Cancer (SCLC) 1 somestatus stop reason just information to hide 3 Not Yet Recruiting Treatment Relapsed Small Cell Lung Cancer (SCLC) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, lyophilized, for solution Intravenous .5 mg/1mL Powder Intravenous 4 mg / vial Injection, powder, lyophilized, for solution Intravenous 4.0 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7763615 No 2010-07-27 2024-12-13 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0646 mg/mL ALOGPS logP 2.65 ALOGPS logP 4.52 Chemaxon logS -4.1 ALOGPS pKa (Strongest Acidic) 9.35 Chemaxon pKa (Strongest Basic) 7.2 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 11 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 164.28 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 205.9 m3·mol-1 Chemaxon Polarizability 81.25 Å3 Chemaxon Number of Rings 10 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 273.2524055 predictedDarkChem Lite v0.1.0 [M-H]- 271.73566 predictedDeepCCS 1.0 (2019) [M+H]+ 271.6111055 predictedDarkChem Lite v0.1.0 [M+H]+ 273.45938 predictedDeepCCS 1.0 (2019) [M+Na]+ 273.7857055 predictedDarkChem Lite v0.1.0 [M+Na]+ 279.7883 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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Unknown
Adduct
References
- FDA Approved Drug Products: Zepzelca (lurbinectedin) for intravenous injection [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- FDA Approved Drug Products: Zepzelca (lurbinectedin) for intravenous injection [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- 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
- FDA Approved Drug Products: Zepzelca (lurbinectedin) for intravenous injection [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- 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
- FDA Approved Drug Products: Zepzelca (lurbinectedin) for intravenous injection [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- FDA Approved Drug Products: Zepzelca (lurbinectedin) for intravenous injection [Link]
- 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
- FDA Approved Drug Products: Zepzelca (lurbinectedin) for intravenous injection [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
- FDA Approved Drug Products: Zepzelca (lurbinectedin) for intravenous injection [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:11388889, PubMed:11408531, PubMed:12439218, PubMed:12719534, PubMed:15389554, PubMed:16263091, PubMed:16272756, PubMed:16581093, PubMed:19536068, PubMed:21128598, PubMed:23680637, PubMed:24961373, PubMed:34040533, PubMed:9187257, PubMed:9260930, PubMed:9655880). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation (PubMed:16263091). Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline (PubMed:12439218, PubMed:24961373, PubMed:35469921, PubMed:9260930). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover (PubMed:21128598). Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism (PubMed:24961373). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency (PubMed:17460754). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (Probable). Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:11408531, PubMed:15389554, PubMed:35469921, PubMed:9260930)
- Specific Function
- (r)-carnitine transmembrane transporter activity
- Gene Name
- SLC22A1
- Uniprot ID
- O15245
- Uniprot Name
- Solute carrier family 22 member 1
- Molecular Weight
- 61153.345 Da
References
- FDA Approved Drug Products: Zepzelca (lurbinectedin) for intravenous injection [Link]
Drug created at October 20, 2016 23:34 / Updated at April 23, 2024 11:38