Relebactam
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Identification
- Summary
Relebactam is a beta-lactamase inhibitor used to prevent hydrolysis of beta-lactam antibiotics, leading to increased effectiveness.
- Brand Names
- Recarbrio
- Generic Name
- Relebactam
- DrugBank Accession Number
- DB12377
- Background
Relebactam is a diazabicyclooctane beta-lactamase inhibitor, similar in structure to avibactam.5,6 It includes a piperidine ring which reduces export from bacterial cells by producing a positive charge.6 It is currently available in a combination product which includes imipenem and cilastatin to treat complicated urinary tract infections (UTIs), pyelonephritis, and complicated intra-abdominal infections in adults.Label It is considered to be a last-line treatment option and gained FDA approval as part of the combination product RecarbrioⓇ in July 2019.9
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 348.37
Monoisotopic: 348.110355554 - Chemical Formula
- C12H20N4O6S
- Synonyms
- Relebactam
- Relebactam anhydrous
- External IDs
- MK-7655
Pharmacology
- Indication
Relebactam is indicated in combination with imipenem and cilastatin for the treatment of complicated urinary tract infections (including pyelonephritis), and complicated intra-abdominal infections caused by susceptible organisms in adults.Label
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 Complicated intra-abdominal infection •••••••••••• ••••• ••••••••• Treatment of Pyelonephritis •••••••••••• ••••• ••••••••• Treatment of Complicated uti •••••••••••• ••••• ••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Relebactam prevents the hydrolysis of imipenem, allowing it to exert its bactericidal effect.
- Mechanism of action
Relebactam is a beta-lactamase inhibitor known to inhibit many types of beta-lactamases including Ambler class A and Ambler class C enzymes, helping to prevent imipenem from degrading in the body.Label,3,4,5 Similar to the structurally-related avibactam, first, relebactam binds non-covalently to a beta-lactamase binding site, then, it covalently acylates the serine residue in the active site of the enzyme.2,5,7 In contrast to some other beta-lactamase inhibitors, once relebactam de-acylates from the active site, it can reform it's 5 membered ring and is capable of rebinding to target enzymes.5
Target Actions Organism ABeta-lactamase inhibitorStaphylococcus aureus ABeta-lactamase TEM inhibitorEscherichia coli ABeta-lactamase SHV-1 inhibitorEscherichia coli ABeta-lactamase CTX-M inhibitorEscherichia coli ABeta-lactamase inhibitorKlebsiella pneumoniae ABeta-lactamase inhibitorEnterobacter cloacae - Absorption
Currently, relebactam is only available as an intravenous product; therefore, there is no relevant absorption data in the literature.
- Volume of distribution
Relebactam has a volume of distribution of approximately 19 L with both single and steady state dosing.Label,1,2
- Protein binding
Relebactam is approximately 22% plasma protein bound.Label,8
- Metabolism
Relebactam does not undergo significant metabolism and can be found mostly unchanged in human plasma.Label
- Route of elimination
Approximately 90-100% of relebactam is renally eliminated.Label,1,2
- Half-life
Relebactam has a half-life of 1.2 hours as per official FDA labeling.Label Values reported in pharmacokinetic studies vary from 1.35-1.8 hours.1,2
- Clearance
Relebactam has a reported total clearance of approximately 130-150 mL/min (8 L/h).Label,1,2 About 30% of the total drug clearance can be attributed to active tubular secretion.Label
- 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
If overdose with the combination product which includes relebactam, imipenem and cilastatin occurs, the drug should be stopped immediately and the patient should be provided with supportive care.Label Relebactam, imipenem, and cilastatin may be removed via hemodialysis; however, the use of hemodialysis to manage cases of overdose has not been studied.Label
- 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 softwareAbemaciclib The excretion of Abemaciclib can be decreased when combined with Relebactam. Acetylsalicylic acid The excretion of Relebactam can be decreased when combined with Acetylsalicylic acid. Acyclovir The excretion of Relebactam can be decreased when combined with Acyclovir. Aminohippuric acid The excretion of Relebactam can be decreased when combined with Aminohippuric acid. Apalutamide The excretion of Relebactam can be decreased when 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.
- Product Ingredients
Ingredient UNII CAS InChI Key Relebactam sodium EX0546AJ8R 1502858-91-4 MMUZXOWPDRLGBD-UXQCFNEQSA-M - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Recarbrio Relebactam (250 mg/100mL) + Cilastatin (500 mg/100mL) + Imipenem (500 mg/100mL) Injection, powder, for solution Intravenous Merck Sharp & Dohme B.V. 2020-01-06 Not applicable US Recarbrio Relebactam (250 mg) + Cilastatin sodium (500 mg) + Imipenem monohydrate (500 mg) Injection, powder, for solution Intravenous Merck Sharp & Dohme B.V. 2020-12-23 Not applicable EU RECARBRIO Relebactam (250 MG) + Cilastatin (500 MG) + Imipenem (500 MG) Powder, for solution Intravenous Merck Sharp & Dohme B.V. 2020-05-11 Not applicable Italy
Categories
- ATC Codes
- J01DH56 — Imipenem, cilastatin and relebactam
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Alpha amino acid amides
- Alternative Parents
- Piperidinecarboxamides / 1,3-diazepanes / Imidazolidinones / Organic sulfuric acids and derivatives / Secondary carboxylic acid amides / Dialkylamines / Azacyclic compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- 1,3-diazepane / 2-piperidinecarboxamide / Aliphatic heteropolycyclic compound / Alpha-amino acid amide / Amine / Azacycle / Carbonyl group / Carboxamide group / Diazepane / Hydrocarbon derivative
- Molecular Framework
- Aliphatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Pseudomonas aeruginosa
- Escherichia coli
- Bacteroides fragilis
- Enterobacter cloacae
- Klebsiella pneumoniae
- Klebsiella oxytoca
- Citrobacter freundii
- Bacteroides thetaiotaomicron
- Klebsiella aerogenes
- Bacteroides caccae
- Bacteroides ovatus
- Bacteroides stercoris
- Bacteroides uniformis
- Bacteroides vulgatus
- Fusobacterium nucleatum
- Parabacteroides distasonis
Chemical Identifiers
- UNII
- 1OQF7TT3PF
- CAS number
- 1174018-99-5
- InChI Key
- SMOBCLHAZXOKDQ-ZJUUUORDSA-N
- InChI
- InChI=1S/C12H20N4O6S/c17-11(14-8-3-5-13-6-4-8)10-2-1-9-7-15(10)12(18)16(9)22-23(19,20)21/h8-10,13H,1-7H2,(H,14,17)(H,19,20,21)/t9-,10+/m1/s1
- IUPAC Name
- [(1R,2S,5R)-7-oxo-2-[(piperidin-4-yl)carbamoyl]-1,6-diazabicyclo[3.2.1]octan-6-yl]oxidanesulfonic acid
- SMILES
- OS(=O)(=O)ON1[C@H]2C[N@]([C@@H](CC2)C(=O)NC2CCNCC2)C1=O
References
- General References
- Rhee EG, Rizk ML, Calder N, Nefliu M, Warrington SJ, Schwartz MS, Mangin E, Boundy K, Bhagunde P, Colon-Gonzalez F, Jumes P, Liu Y, Butterton JR: Pharmacokinetics, Safety, and Tolerability of Single and Multiple Doses of Relebactam, a beta-Lactamase Inhibitor, in Combination with Imipenem and Cilastatin in Healthy Participants. Antimicrob Agents Chemother. 2018 Aug 27;62(9). pii: AAC.00280-18. doi: 10.1128/AAC.00280-18. Print 2018 Sep. [Article]
- Crass RL, Pai MP: Pharmacokinetics and Pharmacodynamics of beta-Lactamase Inhibitors. Pharmacotherapy. 2019 Feb;39(2):182-195. doi: 10.1002/phar.2210. Epub 2019 Jan 20. [Article]
- Papp-Wallace KM, Barnes MD, Alsop J, Taracila MA, Bethel CR, Becka SA, van Duin D, Kreiswirth BN, Kaye KS, Bonomo RA: Relebactam Is a Potent Inhibitor of the KPC-2 beta-Lactamase and Restores Imipenem Susceptibility in KPC-Producing Enterobacteriaceae. Antimicrob Agents Chemother. 2018 May 25;62(6). pii: AAC.00174-18. doi: 10.1128/AAC.00174-18. Print 2018 Jun. [Article]
- Barnes MD, Bethel CR, Alsop J, Becka SA, Rutter JD, Papp-Wallace KM, Bonomo RA: Inactivation of the Pseudomonas-Derived Cephalosporinase-3 (PDC-3) by Relebactam. Antimicrob Agents Chemother. 2018 Apr 26;62(5). pii: AAC.02406-17. doi: 10.1128/AAC.02406-17. Print 2018 May. [Article]
- Zhanel GG, Lawrence CK, Adam H, Schweizer F, Zelenitsky S, Zhanel M, Lagace-Wiens PRS, Walkty A, Denisuik A, Golden A, Gin AS, Hoban DJ, Lynch JP 3rd, Karlowsky JA: Imipenem-Relebactam and Meropenem-Vaborbactam: Two Novel Carbapenem-beta-Lactamase Inhibitor Combinations. Drugs. 2018 Jan;78(1):65-98. doi: 10.1007/s40265-017-0851-9. [Article]
- Jones JA, Virga KG, Gumina G, Hevener KE: Recent Advances in the Rational Design and Optimization of Antibacterial Agents. Medchemcomm. 2016 Sep 1;7(9):1694-1715. doi: 10.1039/C6MD00232C. Epub 2016 Jul 7. [Article]
- Wong D, van Duin D: Novel Beta-Lactamase Inhibitors: Unlocking Their Potential in Therapy. Drugs. 2017 Apr;77(6):615-628. doi: 10.1007/s40265-017-0725-1. [Article]
- Rizk ML, Rhee EG, Jumes PA, Gotfried MH, Zhao T, Mangin E, Bi S, Chavez-Eng CM, Zhang Z, Butterton JR: Intrapulmonary Pharmacokinetics of Relebactam, a Novel beta-Lactamase Inhibitor, Dosed in Combination with Imipenem-Cilastatin in Healthy Subjects. Antimicrob Agents Chemother. 2018 Feb 23;62(3). pii: AAC.01411-17. doi: 10.1128/AAC.01411-17. Print 2018 Mar. [Article]
- FDA Approved Drug Products: Recarbrio (imipenem, cilastatin, and relebactam) for intravenous injection [Link]
- External Links
- PubChem Compound
- 44129647
- PubChem Substance
- 347828625
- ChemSpider
- 31137585
- BindingDB
- 1858
- 2268500
- ChEMBL
- CHEMBL3112741
- ZINC
- ZINC000043206319
- Wikipedia
- Relebactam
- MSDS
- Download (211 KB)
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 Unknown Status Not Available Ceftolozane/Tazobactam / Hematology and Oncology / Imipenem/Relebactam 1 somestatus stop reason just information to hide 4 Enrolling by Invitation Other Critically Ill Patients / Obesity 1 somestatus stop reason just information to hide 4 Recruiting Other Bacterial Pneumonia / Cystic Fibrosis (CF) 1 somestatus stop reason just information to hide 4 Withdrawn Treatment Antibiotic Resistant Infection / Carbapenem Resistant Enterobacteriaceae Infection / Gram-Negative Bacterial Infections / KPC 1 somestatus stop reason just information to hide 3 Completed Treatment Bacterial Infections 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous Powder, for solution Intravenous - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8487093 No 2013-07-16 2029-11-19 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 2.91 mg/mL ALOGPS logP -2 ALOGPS logP -3.1 Chemaxon logS -2.1 ALOGPS pKa (Strongest Acidic) -2 Chemaxon pKa (Strongest Basic) 10.03 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 128.28 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 77.54 m3·mol-1 Chemaxon Polarizability 32.83 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes 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
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-08is-8591000000-e844715aa3c75905c8ef Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0009000000-26819e10f31a50ea0334 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-0029000000-b0e34f6e712e7f8fc0b4 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0379000000-4f01543f62a41ecb21d8 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0007-9135000000-647e5a97f9e1d8c1d874 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-004l-1912000000-0150cc2e268053373c01 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0005-9251000000-6fe55bb33d9b43b7957f Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 163.24364 predictedDeepCCS 1.0 (2019) [M+H]+ 165.63922 predictedDeepCCS 1.0 (2019) [M+Na]+ 171.97981 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Staphylococcus aureus
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Not Available
- Specific Function
- beta-lactamase activity
- Gene Name
- blaZ
- Uniprot ID
- P00807
- Uniprot Name
- Beta-lactamase
- Molecular Weight
- 31348.98 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Escherichia coli
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- TEM-type are the most prevalent beta-lactamases in enterobacteria; they hydrolyze the beta-lactam bond in susceptible beta-lactam antibiotics, thus conferring resistance to penicillins and cephalosporins. TEM-3 and TEM-4 are capable of hydrolyzing cefotaxime and ceftazidime. TEM-5 is capable of hydrolyzing ceftazidime. TEM-6 is capable of hydrolyzing ceftazidime and aztreonam. TEM-8/CAZ-2, TEM-16/CAZ-7 and TEM-24/CAZ-6 are markedly active against ceftazidime. IRT-4 shows resistance to beta-lactamase inhibitors.
- Specific Function
- beta-lactamase activity
- Gene Name
- bla
- Uniprot ID
- P62593
- Uniprot Name
- Beta-lactamase TEM
- Molecular Weight
- 31514.865 Da
References
- Zhanel GG, Lawrence CK, Adam H, Schweizer F, Zelenitsky S, Zhanel M, Lagace-Wiens PRS, Walkty A, Denisuik A, Golden A, Gin AS, Hoban DJ, Lynch JP 3rd, Karlowsky JA: Imipenem-Relebactam and Meropenem-Vaborbactam: Two Novel Carbapenem-beta-Lactamase Inhibitor Combinations. Drugs. 2018 Jan;78(1):65-98. doi: 10.1007/s40265-017-0851-9. [Article]
- Kind
- Protein
- Organism
- Escherichia coli
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Not Available
- Specific Function
- beta-lactamase activity
- Gene Name
- bla
- Uniprot ID
- P0AD63
- Uniprot Name
- Beta-lactamase SHV-1
- Molecular Weight
- 31223.635 Da
References
- Zhanel GG, Lawrence CK, Adam H, Schweizer F, Zelenitsky S, Zhanel M, Lagace-Wiens PRS, Walkty A, Denisuik A, Golden A, Gin AS, Hoban DJ, Lynch JP 3rd, Karlowsky JA: Imipenem-Relebactam and Meropenem-Vaborbactam: Two Novel Carbapenem-beta-Lactamase Inhibitor Combinations. Drugs. 2018 Jan;78(1):65-98. doi: 10.1007/s40265-017-0851-9. [Article]
- Kind
- Protein group
- Organism
- Escherichia coli
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Not Available
- Specific Function
- beta-lactamase activity
Components:
References
- Zhanel GG, Lawrence CK, Adam H, Schweizer F, Zelenitsky S, Zhanel M, Lagace-Wiens PRS, Walkty A, Denisuik A, Golden A, Gin AS, Hoban DJ, Lynch JP 3rd, Karlowsky JA: Imipenem-Relebactam and Meropenem-Vaborbactam: Two Novel Carbapenem-beta-Lactamase Inhibitor Combinations. Drugs. 2018 Jan;78(1):65-98. doi: 10.1007/s40265-017-0851-9. [Article]
- Kind
- Protein
- Organism
- Klebsiella pneumoniae
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Not Available
- Specific Function
- beta-lactamase activity
- Gene Name
- KPC-2
- Uniprot ID
- Q93LQ9
- Uniprot Name
- Beta-lactamase
- Molecular Weight
- 31114.99 Da
References
- Zhanel GG, Lawrence CK, Adam H, Schweizer F, Zelenitsky S, Zhanel M, Lagace-Wiens PRS, Walkty A, Denisuik A, Golden A, Gin AS, Hoban DJ, Lynch JP 3rd, Karlowsky JA: Imipenem-Relebactam and Meropenem-Vaborbactam: Two Novel Carbapenem-beta-Lactamase Inhibitor Combinations. Drugs. 2018 Jan;78(1):65-98. doi: 10.1007/s40265-017-0851-9. [Article]
- Kind
- Protein
- Organism
- Enterobacter cloacae
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
- Specific Function
- beta-lactamase activity
- Gene Name
- ampC
- Uniprot ID
- P05364
- Uniprot Name
- Beta-lactamase
- Molecular Weight
- 41301.33 Da
References
- Zhanel GG, Lawrence CK, Adam H, Schweizer F, Zelenitsky S, Zhanel M, Lagace-Wiens PRS, Walkty A, Denisuik A, Golden A, Gin AS, Hoban DJ, Lynch JP 3rd, Karlowsky JA: Imipenem-Relebactam and Meropenem-Vaborbactam: Two Novel Carbapenem-beta-Lactamase Inhibitor Combinations. Drugs. 2018 Jan;78(1):65-98. doi: 10.1007/s40265-017-0851-9. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
- Specific Function
- organic anion transmembrane transporter activity
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Organic anion transporter 3
- Molecular Weight
- 59855.585 Da
References
- Chan G, Houle R, Lin M, Yabut J, Cox K, Wu J, Chu X: Role of transporters in the disposition of a novel beta-lactamase inhibitor: relebactam (MK-7655). J Antimicrob Chemother. 2019 Jul 1;74(7):1894-1903. doi: 10.1093/jac/dkz101. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Antiporter that mediates the transport of conjugated steroids and other specific organic anions at the basal membrane of syncytiotrophoblast and at the apical membrane of proximal tubule epithelial cells, in exchange for anionic compounds (PubMed:10660625, PubMed:11907186, PubMed:15037815, PubMed:15102942, PubMed:15291761, PubMed:15576633, PubMed:17229912, PubMed:18501590, PubMed:26277985, PubMed:28027879). May be responsible for placental absorption of fetal-derived steroid sulfates such as estrone sulfate (E1S) and the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S), as well as clearing waste products and xenobiotics from the fetus (PubMed:12409283). Maybe also be involved in placental urate homeostasis (PubMed:17229912). Facilitates the renal reabsorption of organic anions such as urate and derived steroid sulfates (PubMed:15037815, PubMed:17229912). Organic anion glutarate acts as conteranion for E1S renal uptake (PubMed:15037815, PubMed:17229912). Possible transport mode may also include DHEA-S/E1S exchange (PubMed:28027879). Also interacts with inorganic anions such as chloride and hydroxyl ions, therefore possible transport modes may include E1S/Cl(-), E1S/OH(-), urate/Cl(-) and urate/OH(-) (PubMed:17229912). Also mediates the transport of prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may be involved in their renal excretion (PubMed:11907186). Also able to uptake anionic drugs, diuretics, bile salts and ochratoxin A (PubMed:10660625, PubMed:26277985). Mediates the unidirectional efflux of glutamate and aspartate (PubMed:28027879). Glutamate efflux down its transmembrane gradient may drive SLC22A11/OAT4-mediated placental uptake of E1S (PubMed:26277985)
- Specific Function
- organic anion transmembrane transporter activity
- Gene Name
- SLC22A11
- Uniprot ID
- Q9NSA0
- Uniprot Name
- Solute carrier family 22 member 11
- Molecular Weight
- 59970.945 Da
References
- Chan G, Houle R, Lin M, Yabut J, Cox K, Wu J, Chu X: Role of transporters in the disposition of a novel beta-lactamase inhibitor: relebactam (MK-7655). J Antimicrob Chemother. 2019 Jul 1;74(7):1894-1903. doi: 10.1093/jac/dkz101. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Multidrug efflux pump that functions as a H(+)/organic cation antiporter (PubMed:16330770, PubMed:17509534). Plays a physiological role in the excretion of cationic compounds including endogenous metabolites, drugs, toxins through the kidney and liver, into urine and bile respectively (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). Mediates the efflux of endogenous compounds such as creatinine, vitamin B1/thiamine, agmatine and estrone-3-sulfate (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). May also contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable)
- Specific Function
- antiporter activity
- Gene Name
- SLC47A1
- Uniprot ID
- Q96FL8
- Uniprot Name
- Multidrug and toxin extrusion protein 1
- Molecular Weight
- 61921.585 Da
References
- Chan G, Houle R, Lin M, Yabut J, Cox K, Wu J, Chu X: Role of transporters in the disposition of a novel beta-lactamase inhibitor: relebactam (MK-7655). J Antimicrob Chemother. 2019 Jul 1;74(7):1894-1903. doi: 10.1093/jac/dkz101. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Multidrug efflux pump that functions as a H(+)/organic cation antiporter. Mediates the efflux of cationic compounds, such as the model cations, tetraethylammonium (TEA) and 1-methyl-4-phenylpyridinium (MPP+), the platinum-based drug oxaliplatin or weak bases that are positively charged at physiological pH, cimetidine, the platinum-based drugs cisplatin and oxaliplatin or the antidiabetic drug metformin. Mediates the efflux of endogenous compounds such as, creatinine, thiamine and estrone-3-sulfate. Plays a physiological role in the excretion of drugs, toxins and endogenous metabolites through the kidney
- Specific Function
- antiporter activity
- Gene Name
- SLC47A2
- Uniprot ID
- Q86VL8
- Uniprot Name
- Multidrug and toxin extrusion protein 2
- Molecular Weight
- 65083.915 Da
References
- Chan G, Houle R, Lin M, Yabut J, Cox K, Wu J, Chu X: Role of transporters in the disposition of a novel beta-lactamase inhibitor: relebactam (MK-7655). J Antimicrob Chemother. 2019 Jul 1;74(7):1894-1903. doi: 10.1093/jac/dkz101. [Article]
Drug created at October 20, 2016 22:08 / Updated at August 26, 2024 19:23