Doripenem
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Identification
- Summary
Doripenem is an antibiotic of the penem class used to treat complicated intra-abdominal and urinary tract infections.
- Generic Name
- Doripenem
- DrugBank Accession Number
- DB06211
- Background
Doripenem is a broad-spectrum, carbapenem antibiotic marketed under the brand name Doribax by Janssen. Doripenem injection was approved by the FDA in 2007 to treat complicated urinary tract and intra-abdominal infections. In a clinical trial of doripenem treatment in ventilator associated pneumonia (vs. imipenem and cilastatin), it was found that doripenem carried an increased risk of death and lower clinical cure rates, resulting in a premature termination of the trial. The FDA revised the doripenem label in 2014 to include a warning against use in ventilator-associated pneumonia and to reiterate its safety and efficacy for its approved indications.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 420.504
Monoisotopic: 420.1137259 - Chemical Formula
- C15H24N4O6S2
- Synonyms
- Doripenem
- External IDs
- S 4661
- S-4661
Pharmacology
- Indication
Doripenem is indicated in the treatment of complicated intra-abdominal infections and complicated urinary tract infections, including pyelonephritis, caused by designated susceptible bacteria.
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 Bacterial infections •••••••••••• Treatment of Catheter-related bloodstream infection ••• ••••• Treatment of Complicated intra-abdominal infections •••••••••••• Treatment of Complicated urinary tract infections •••••••••••• Treatment of Pyelonephritis •••••••••••• - 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
Similar to other beta-lactam antimicrobial agents, the time that unbound plasma concentration of doripenem exceeds the MIC (T>MIC) of the infecting organism has been shown to best correlate with efficacy in animal models of infection.
- Mechanism of action
Doripenem is a broad-spectrum carbapenem antibiotic with activity against many gram-positive and gram-negative aerobic bacteria, as well as a variety of anaerobes. Like other beta-lactam antibiotics, doripenem's bactericidal mechanism of action is mostly due to cell death after inhibition of bacterial enzymes called penicillin-bindng proteins (PBPs), which are responsible for peptidoglycan cross-linking during the synthesis of the bacterial cell wall. Carbapenems mainly have high affinity for PBPs 1a, 1b, 2 and 3. Inhibition of each PBP usually results in a different inactivating mechanism. Inhibition of PBPs 1a and 1b results in fast bacterial killing through the formation of spheroplasts, inhibition of PBP 2 results in rod-shaped bacteria to become spherical, and inhibition of PBP 3 results in filamentous-shaped organisms. The PBPs preferentially bound by different carbapenems depend on the organism. In E.coli and P.aeruginosa, doripenem binds to PBP 2, which is involved in the maintenance of cell shape, as well as to PBPs 3 and 4. Doripenem has a 1-beta-methyl side chain, which allows it to be relatively resistant to dehydropeptidase, as well as a trans-alpha-1-hydroxyethyl group at position 6 which provides beta-lactamase resistance. Like other carbapenems, doripenem is different from most beta-lactams due to its stability against hydrolysis by most beta-lactamases, including penicillinases, cephalosporinases, ESBL, and Amp-C producing enterobacteriaceae.
Target Actions Organism ADihydropteroate synthase inhibitorEscherichia coli (strain K12) APenicillin-binding protein 1A antagonistinhibitorEscherichia coli (strain K12) APenicillin-binding protein 1B antagonistinhibitorEscherichia coli (strain K12) APenicillin-binding protein 2 antagonistinhibitorEscherichia coli (strain K12) ACell division protein antagonistinhibitorPseudomonas aeruginosa APenicillin-binding protein 4 antagonistinhibitorStaphylococcus aureus - Absorption
Doripenem is administered intravenously as an infusion. There was no accumulation of doripenem following mulitiple infusions of either 500mg or 1g administered every 8 hours for 7-10 days in subjects with normal renal function.
- Volume of distribution
The average Vd is 16.8 L (8.09-55.5 L) at steady-state in healthy subjects. Doripenem penetrates into many tissues and fluids, including potential sites of approved indication infections.
- Protein binding
8.1%
- Metabolism
Metabolism of doripenem is via dehydropeptidase-I (also called dipeptidase-1) into a microbiologically inactive ring-opened metabolite, doripenem-M1. Doripenem does not appear to be a substrate of the hepatic CYP450 enzymes.
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- Route of elimination
Doripenem is primarily eliminated unchanged by the kidneys and undergoes glomerular filtration and active tubular secretion. A mean of 71% and 15% of the dose was recovered in urine as unchanged drug and the ring-opened metabolite, respectively, within 48 hours of 500 mg dose in healthy adults. Following the administration of a single 500 mg dose of radiolabeled doripenem to healthy adults, less than 1% of the total radioactivity was recovered in feces after one week.
- Half-life
1 hour, in healthy non-elderly adults.
- Clearance
10.3 L/hour.
- Adverse Effects
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- Toxicity
Dosage adjustment is necessary in patients with moderate and severe renal impairment.
Doripenem's FDA label includes a warning against use in ventilator-associated bacterial pneumonia, as a clinical trial for that indication resulted in increased mortality with doripenem (23% vs. 16.7% recieving imipenem) as well as lower clinical response rates.
Seizures have been reported with doripenem treatment; patients at greater risk of developing seizures we found to have pre-existing central nervous system (CNS) conditions, compromised renal function, or patients receiving higher doses than 500 mg every 8 hours. Doripenem also reduces plasma levels of valproic acid when administered concomitantly; therefore patients with pre-existing seizure disorders on valproic acid are at even higher risk of breakthrough seizures if receiving both drugs at the same time.
Doripenem is considered pregnancy category B as it was not found to be teratogenic or produce effects on ossification, developmental delays, or fetal weight in rat and rabbit studies. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. It is not known whether doripenem is excreted into breast milk, therefore caution should be exercised with doripenem administration to nursing women.
- 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 softwareAbacavir Abacavir may decrease the excretion rate of Doripenem which could result in a higher serum level. Aceclofenac Aceclofenac may decrease the excretion rate of Doripenem which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Doripenem which could result in a higher serum level. Acenocoumarol The risk or severity of bleeding can be increased when Doripenem is combined with Acenocoumarol. Acetaminophen Acetaminophen may decrease the excretion rate of Doripenem which could result in a higher serum level. - 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 Doripenem hydrate 4B035T6NKT 364622-82-2 NTUBEBXBDGKBTJ-WGLOMNHJSA-N - International/Other Brands
- Finibax (Shionogi Co.)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Doribax Powder, for solution 500 mg / vial Intravenous Janssen Pharmaceuticals 2009-10-19 2013-07-03 Canada Doribax Powder, for solution 500 mg/10mL Intravenous Janssen Pharmaceuticals 2007-10-12 2014-07-30 US Doribax Injection, powder, for solution 250 mg Intravenous Janssen Cilag International Nv 2016-09-08 2014-07-31 EU Doribax Powder, for solution 250 mg/10mL Intravenous Shionogi 2010-10-15 2020-02-28 US Doribax Powder, for solution 500 mg/10mL Intravenous Ortho-McNeil-Janssen Pharmaceuticals, Inc. 2007-10-12 2011-02-28 US
Categories
- ATC Codes
- J01DH04 — Doripenem
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as thienamycins. These are beta-lactam antibiotics that differ from penicillins in having the thiazolidine sulfur atom replaced by carbon, the sulfur then becoming the first atom in the side chain.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Lactams
- Sub Class
- Beta lactams
- Direct Parent
- Thienamycins
- Alternative Parents
- Alpha amino acids and derivatives / Pyrroline carboxylic acids / Azepines / Vinylogous thioesters / Sulfuric acid diamides / Tertiary carboxylic acid amides / Pyrrolidines / Thioenol ethers / Secondary alcohols / Amino acids show 10 more
- Substituents
- Alcohol / Aliphatic heteropolycyclic compound / Alpha-amino acid or derivatives / Amine / Amino acid / Amino acid or derivatives / Azacycle / Azepine / Azetidine / Carbonyl group show 26 more
- Molecular Framework
- Aliphatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Various aerobic and anaerobic microorganisms
- Pseudomonas aeruginosa
- Streptococcus pneumoniae
- Haemophilus influenzae
- Escherichia coli
- Staphylococcus aureus
- Enterococcus faecalis
- Moraxella catarrhalis
- Acinetobacter
- Enterococcus faecium
- Klebsiella
- Enterobacter
- Streptococcus constellatus
- Proteus mirabilis
Chemical Identifiers
- UNII
- BHV525JOBH
- CAS number
- 148016-81-3
- InChI Key
- AVAACINZEOAHHE-VFZPANTDSA-N
- InChI
- InChI=1S/C15H24N4O6S2/c1-6-11-10(7(2)20)14(21)19(11)12(15(22)23)13(6)26-9-3-8(17-5-9)4-18-27(16,24)25/h6-11,17-18,20H,3-5H2,1-2H3,(H,22,23)(H2,16,24,25)/t6-,7-,8+,9+,10-,11-/m1/s1
- IUPAC Name
- (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-{[(3S,5S)-5-[(sulfamoylamino)methyl]pyrrolidin-3-yl]sulfanyl}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
- SMILES
- [H][C@]12[C@@H](C)C(S[C@@H]3CN[C@H](CNS(N)(=O)=O)C3)=C(N1C(=O)[C@]2([H])[C@@H](C)O)C(O)=O
References
- General References
- Jones RN, Huynh HK, Biedenbach DJ: Activities of doripenem (S-4661) against drug-resistant clinical pathogens. Antimicrob Agents Chemother. 2004 Aug;48(8):3136-40. [Article]
- Chahine EB, Ferrill MJ, Poulakos MN: Doripenem: a new carbapenem antibiotic. Am J Health Syst Pharm. 2010 Dec 1;67(23):2015-24. doi: 10.2146/ajhp090672. [Article]
- Dedhia HV, McKnight R: Doripenem: position in clinical practice. Expert Rev Anti Infect Ther. 2009 Jun;7(5):507-14. doi: 10.1586/eri.09.37. [Article]
- Matthews SJ, Lancaster JW: Doripenem monohydrate, a broad-spectrum carbapenem antibiotic. Clin Ther. 2009 Jan;31(1):42-63. doi: 10.1016/j.clinthera.2009.01.013. [Article]
- External Links
- Human Metabolome Database
- HMDB0041883
- KEGG Drug
- D03895
- PubChem Compound
- 73303
- PubChem Substance
- 310264862
- ChemSpider
- 66040
- BindingDB
- 50088382
- 119771
- ChEBI
- 135928
- ChEMBL
- CHEMBL491571
- ZINC
- ZINC000003922770
- PDBe Ligand
- O6P
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Doripenem
- PDB Entries
- 6p9c
- FDA label
- Download (868 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 Completed Not Available Bacterial Pneumonia / Hospital Acquired Infections / Intraabdominal Infections / Urinary Tract Infection 1 somestatus stop reason just information to hide Not Available Completed Treatment Septic Shock 1 somestatus stop reason just information to hide 4 Completed Not Available Healthy Volunteers (HV) 1 somestatus stop reason just information to hide 4 Completed Not Available Ventilator Associated Bacterial Pneumonia (VABP) 1 somestatus stop reason just information to hide 4 Completed Treatment Bacterial Infections / Crossing Infections / Infection / Intraabdominal Infections / Urinary Tract Infection / Ventilator Associated Bacterial Pneumonia (VABP) 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 500 mg Injection, powder, for solution Intravenous 250 mg Powder, for solution Intravenous Powder, for solution Intravenous 250 mg/10mL Powder, for solution Intravenous 500 mg/10mL Powder, for solution Intravenous 500 mg / vial Injection, powder, lyophilized, for suspension Intravenous 500 mg Injection, powder, for solution Intravenous 500 mg/1vial Injection, powder, for solution Intravenous 0.5 g Injection, powder, for solution Intravenous 522 mg Injection, powder, lyophilized, for solution Intravenous 0.5 g Injection, powder, for solution Intravenous 500 mg/ml Injection, powder, for solution Intravenous 500 mg Powder 500 mg/1vial - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5317016 No 1994-05-31 2012-08-14 US CA2404703 No 2007-06-05 2021-03-30 Canada CA2076430 No 1997-12-23 2012-08-19 Canada US8247402 No 2012-08-21 2021-03-30 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 3.13 mg/mL ALOGPS logP -1.3 ALOGPS logP -5.6 Chemaxon logS -2.1 ALOGPS pKa (Strongest Acidic) 3.34 Chemaxon pKa (Strongest Basic) 9.51 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 5 Chemaxon Polar Surface Area 162.06 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 99.88 m3·mol-1 Chemaxon Polarizability 42.37 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 Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption - 0.6542 Blood Brain Barrier - 0.9633 Caco-2 permeable - 0.6508 P-glycoprotein substrate Substrate 0.7634 P-glycoprotein inhibitor I Non-inhibitor 0.8733 P-glycoprotein inhibitor II Non-inhibitor 1.0 Renal organic cation transporter Non-inhibitor 0.9288 CYP450 2C9 substrate Non-substrate 0.7918 CYP450 2D6 substrate Non-substrate 0.8135 CYP450 3A4 substrate Non-substrate 0.6002 CYP450 1A2 substrate Non-inhibitor 0.8052 CYP450 2C9 inhibitor Non-inhibitor 0.7661 CYP450 2D6 inhibitor Non-inhibitor 0.8798 CYP450 2C19 inhibitor Non-inhibitor 0.7305 CYP450 3A4 inhibitor Non-inhibitor 0.9118 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9886 Ames test Non AMES toxic 0.6139 Carcinogenicity Non-carcinogens 0.6727 Biodegradation Not ready biodegradable 0.8469 Rat acute toxicity 2.4823 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9799 hERG inhibition (predictor II) Non-inhibitor 0.878
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0f6w-9326200000-4861cde5290eee720492 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-0000900000-258ca1ae4b2e107b65dd Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-0000900000-88d2dda3c7e7a362c794 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-07fu-2139400000-f9eb34c0a65618df90f6 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-0002900000-98e80db2aeca90ecfe1f Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0gc9-1924000000-5ed0dc0a0e09f7f7d0f2 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-004l-8239000000-5f0f0c68ee76c56aa1ed 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]- 208.6857441 predictedDarkChem Lite v0.1.0 [M-H]- 219.3097441 predictedDarkChem Lite v0.1.0 [M-H]- 192.33209 predictedDeepCCS 1.0 (2019) [M+H]+ 210.4421441 predictedDarkChem Lite v0.1.0 [M+H]+ 220.5880441 predictedDarkChem Lite v0.1.0 [M+H]+ 194.2275 predictedDeepCCS 1.0 (2019) [M+Na]+ 209.5828441 predictedDarkChem Lite v0.1.0 [M+Na]+ 218.6886441 predictedDarkChem Lite v0.1.0 [M+Na]+ 200.00545 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Escherichia coli (strain K12)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Catalyzes the condensation of para-aminobenzoate (pABA) with 6-hydroxymethyl-7,8-dihydropterin diphosphate (DHPt-PP) to form 7,8-dihydropteroate (H2Pte), the immediate precursor of folate derivatives.
- Specific Function
- dihydropteroate synthase activity
- Gene Name
- folP
- Uniprot ID
- P0AC13
- Uniprot Name
- Dihydropteroate synthase
- Molecular Weight
- 30614.855 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 (strain K12)
- Pharmacological action
- Yes
- Actions
- AntagonistInhibitor
- General Function
- Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits).
- Specific Function
- penicillin binding
- Gene Name
- mrcA
- Uniprot ID
- P02918
- Uniprot Name
- Penicillin-binding protein 1A
- Molecular Weight
- 93635.545 Da
References
- Matthews SJ, Lancaster JW: Doripenem monohydrate, a broad-spectrum carbapenem antibiotic. Clin Ther. 2009 Jan;31(1):42-63. doi: 10.1016/j.clinthera.2009.01.013. [Article]
- Kind
- Protein
- Organism
- Escherichia coli (strain K12)
- Pharmacological action
- Yes
- Actions
- AntagonistInhibitor
- General Function
- Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits).
- Specific Function
- penicillin binding
- Gene Name
- mrcB
- Uniprot ID
- P02919
- Uniprot Name
- Penicillin-binding protein 1B
- Molecular Weight
- 94291.875 Da
References
- Matthews SJ, Lancaster JW: Doripenem monohydrate, a broad-spectrum carbapenem antibiotic. Clin Ther. 2009 Jan;31(1):42-63. doi: 10.1016/j.clinthera.2009.01.013. [Article]
- Kind
- Protein
- Organism
- Escherichia coli (strain K12)
- Pharmacological action
- Yes
- Actions
- AntagonistInhibitor
- General Function
- Catalyzes cross-linking of the peptidoglycan cell wall (PubMed:3009484). Responsible for the determination of the rod shape of the cell (PubMed:1103132). Is probably required for lateral peptidoglycan synthesis and maintenance of the correct diameter during lateral and centripetal growth (PubMed:12519203).
- Specific Function
- penicillin binding
- Gene Name
- mrdA
- Uniprot ID
- P0AD65
- Uniprot Name
- Penicillin-binding protein 2
- Molecular Weight
- 70856.1 Da
References
- Matthews SJ, Lancaster JW: Doripenem monohydrate, a broad-spectrum carbapenem antibiotic. Clin Ther. 2009 Jan;31(1):42-63. doi: 10.1016/j.clinthera.2009.01.013. [Article]
- Kind
- Protein
- Organism
- Pseudomonas aeruginosa
- Pharmacological action
- Yes
- Actions
- AntagonistInhibitor
- General Function
- Catalyzes cross-linking of the peptidoglycan cell wall at the division septum.
- Specific Function
- penicillin binding
- Gene Name
- pbpB
- Uniprot ID
- Q51504
- Uniprot Name
- Cell division protein
- Molecular Weight
- 62855.78 Da
References
- Matthews SJ, Lancaster JW: Doripenem monohydrate, a broad-spectrum carbapenem antibiotic. Clin Ther. 2009 Jan;31(1):42-63. doi: 10.1016/j.clinthera.2009.01.013. [Article]
- Kind
- Protein
- Organism
- Staphylococcus aureus
- Pharmacological action
- Yes
- Actions
- AntagonistInhibitor
- General Function
- Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors.
- Specific Function
- beta-lactamase activity
- Gene Name
- pbp4
- Uniprot ID
- P72355
- Uniprot Name
- Penicillin-binding protein 4
- Molecular Weight
- 48237.14 Da
References
- Dedhia HV, McKnight R: Doripenem: position in clinical practice. Expert Rev Anti Infect Ther. 2009 Jun;7(5):507-14. doi: 10.1586/eri.09.37. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Hydrolyzes a wide range of dipeptides including the conversion of leukotriene D4 to leukotriene E4 (PubMed:2303490, PubMed:31442408, PubMed:32325220, PubMed:6334084). Hydrolyzes cystinyl-bis-glycine (cys-bis-gly) formed during glutathione degradation (PubMed:32325220). Possesses also beta lactamase activity and can hydrolyze the beta-lactam antibiotic imipenem (PubMed:32325220, PubMed:6334084)
- Specific Function
- beta-lactamase activity
- Gene Name
- DPEP1
- Uniprot ID
- P16444
- Uniprot Name
- Dipeptidase 1
- Molecular Weight
- 45673.48 Da
References
- Cirillo I, Mannens G, Janssen C, Vermeir M, Cuyckens F, Desai-Krieger D, Vaccaro N, Kao LM, Devineni D, Redman R, Turner K: Disposition, metabolism, and excretion of [14C]doripenem after a single 500-milligram intravenous infusion in healthy men. Antimicrob Agents Chemother. 2008 Oct;52(10):3478-83. doi: 10.1128/AAC.00424-08. Epub 2008 Jul 21. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- Greer ND: Doripenem (Doribax): the newest addition to the carbapenems. Proc (Bayl Univ Med Cent). 2008 Jul;21(3):337-41. [Article]
Drug created at March 19, 2008 16:17 / Updated at August 26, 2024 19:23