Rifamycin
Explore a selection of our essential drug information below, or:
Overview
- Description
- A medication used to treat traveler's diarrhea.
- Description
- A medication used to treat traveler's diarrhea.
- DrugBank ID
- DB11753
- Type
- Small Molecule
- Clinical Trials
- Phase 0
- 0
- Phase 1
- 3
- Phase 2
- 11
- Phase 3
- 3
- Phase 4
- 3
- Mechanism of Action
Identification
- Summary
Rifamycin is an antibacterial used to treat traveler's diarrhea.
- Brand Names
- Aemcolo
- Generic Name
- Rifamycin
- DrugBank Accession Number
- DB11753
- Background
Rifamycin is the prime member of the rifamycin family which are represented by drugs that are a product of fermentation from the gram-positive bacterium Amycolatopsis mediterranei, also known as Streptomyces mediterranei. The parent compound of rifamycin was rifamycin B which was originally obtained as a main product in the presence of diethylbarburitic acid. Some small modifications where performed in this inactive compound and with the creation of rifamycin SV there was the first antibiotic used intravenously for the treatment of tuberculosis.2
Rifamycin has had several direct derivative products such as rifamycin SV, rifaximin, rifampin and rifamycin CV. All of the derivatives have slight different physicochemical properties when compared to the parent structure.1
Rifamycin was further developed by Cosmo Technologies Ltd and approved in November 16, 2018 by the FDA as a prescription drug after being granted the designation of Qualified Infectious Disease Product which allowed it to have a status a priority review.10 This drug was also sent for review to the EMA in 2015 by Dr. Falk Pharma Gmbh and it was granted a waiver for the tested conditions.11
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 697.778
Monoisotopic: 697.309825957 - Chemical Formula
- C37H47NO12
- Synonyms
- Rifamicina
- Rifamicine SV
- Rifamycin
- Rifamycin SV
- Rifamycine
- Rifamycinum
- Rifomycin SV
- External IDs
- M-14
Pharmacology
- Indication
Rifamycin is indicated for the treatment of adult patients with travelers' diarrhea caused by noninvasive strains of E. coli. The status of the disease should not be complicated by fever or blood in the stool. To prevent drug-resistant bacteria, it is important to mention that the use of rifamycin for this indication should be only done in cases where the infection is proven or strongly suspected to be caused by bacteria.12
Travallers' diarrhea is very common problem affecting 20-60% of the travellers and it is defined as an increase in frequency of bowel movements to three or more loose stools per day during a trip abroad. This condition is rarely life threatening but in severe cases it can produce dehydration and sepsis. The most common cause of travellers' diarrhea is a pathogen and from the pathogens identified, bacteria is the most common cause followed by norovirus, rotavirus and similar viruses.3
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 Not complicated by fever, not complicated by bloody stool traveler's diarrhea caused by noninvasive strains of escherichia coli •••••••••••• ••••• ••••••• •••••••• ••••••• Used in combination to treat Susceptible bacterial infections Combination Product in combination with: Lidocaine (DB00281) •••••••••••• •••••••••• ••••••••• •••••••• - 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
Rifamycin is known to be effective against Gram-positive and Gram-negative pathogens and mycobacteria. It is very effective against E. coli reporting a MIC90 of 64-128 mcg/ml without showing cross-resistance with other antimicrobial agents.4
The specific indication of rifamycin is extremely important as ther were previous reports that indicated a high risk factor in the generation of resistant E. coli strains in patients with inflammatory bowel disease.13
In clinical trials, rifamycin was tested in a randomized clinical trial of travellers' coming from Mexico and Guatemala. In this trial, rifamycin was proven to significantly reduce the symptoms of travellers' diarrhea.12
- Mechanism of action
Rifamycins, as well as all the other members of this group, present an antibacterial mechanism of action related to the inhibition of RNA synthesis. This mechanism of action is done by the strong binding to the DNA-dependent RNA polymerase of prokaryotes. The inhibition of the RNA synthesis is thought to be related with the initiation phase of the process and to involve stacking interactions between the naphthalene ring and the aromatic moiety in the polymerase. As well, it has been suggested that the presence of zinc atoms in the polymerase allows for the binding of phenolic -OH groups of the naphthalene ring.9
In eukaryotic cells, the binding is significantly reduced making them at least 100 to 10,000 times less sensitive to the action of rifamycins. The members of the rifamycin family present the same mechanism of action and the structural modifications are usually related to pharmacokinetic properties as well as to the interaction with eukaryotic cells.8
Target Actions Organism ADNA-directed RNA polymerase subunit beta inhibitorMycobacterium tuberculosis (strain ATCC 25618 / H37Rv) ADNA-directed RNA polymerase subunit beta' inhibitorMycobacterium tuberculosis ADNA-directed RNA polymerase subunit beta binderEscherichia coli (strain K12) ADNA-directed RNA polymerase subunit alpha binderEscherichia coli (strain K12) ADNA-directed RNA polymerase subunit beta' binderEscherichia coli (strain K12) - Absorption
Rifamycin has a very poor absorption4 and thus, the generation of an oral modified-release formulation using the technology of the multi-matrix structure was required for the generation of the FDA approved product. This preparation allows the delivery of the active ingredient in the distal small bowel and colon without interfering with the flora in the upper gastrointestinal tract.5
The multi-matrix is made by a lipophiic matrix surrounded in a hydrophilic matrix which allows for the protection of the active ingredient from dissolution in the intestinal aqueous fluids before it arrives in the cecum. All this matrix is surrounded by a gastro-resistant polymer that only desintegrate in a pH lower than 7.6
All this administration-customed formulation allows for a bioavailability of <0.1% and the plasma concentrations are reported to be of <2 ng/ml in patients receiving a dose of 400 mg. This confirms that the site of action of rifamycin stays in the small intestine and colon which prevents the need for dose adjustments in special populations as well as systemic drug interactions.6
The reported Cmax, tmax, AUC and mean residence time after a dosage of 250 mg of rifamycin is 36 mg/L, 5 min, 11.84 mg.h/L and 0.49 h respectively.6
- Volume of distribution
The reported volume of distribution after measured after a dosage of 250 mg of rifamycin is 101.8 L.6
- Protein binding
The protein binding of rifamycin is of about 80-95%.7
- Metabolism
When absorbed, rifamycin is mainly metabolzied in hepatocytes and intestinal microsomes to a 25-deacetyl metabolite.6
Hover over products below to view reaction partners
- Route of elimination
From the administered dose, 18%, 50% and 21% is recovered in feces during the first 24, 48 and 72h after administration. This will represent about 90% of the administered dose eliminated by the feces while the urinary secretion is negligible.6
- Half-life
The reported half-life when a dose of 250 mg of rifamycin was administered is 3 h.6
- Clearance
The reported clearance when a dose of 250 mg of rifamycin was administered is 23.3 L/h.6
- 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
In safety studies with rifamycin, it was reported a potential of hepatotoxicity due to the depletion of glutathione and the generation of reactive oxygen species in liver microsomes. It is important to mention that this effect is mainly observed in the intravenous administration as the oral dosage does not have a significant systemic absorption.7
Rifamycin is not genotoxic in bacterial mutation assays, mouse cell mutation assay or mouse bone marrow micronucleus assay. There is no current information about the effects on fertility, overdosage or carcinogenesis.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 softwareAcebutolol The metabolism of Acebutolol can be increased when combined with Rifamycin. Acenocoumarol The risk or severity of bleeding can be increased when Rifamycin is combined with Acenocoumarol. Ambroxol The risk or severity of methemoglobinemia can be increased when Rifamycin is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Rifamycin is combined with Articaine. Atenolol The metabolism of Atenolol can be increased when combined with Rifamycin. - Food Interactions
- Avoid alcohol.
- Take with a full glass of water.
- Take 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.
- Product Ingredients
Ingredient UNII CAS InChI Key Rifamycin sodium 32086GS35Z 14897-39-3 YVOFSHPIJOYKSH-NLYBMVFSSA-M - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Aemcolo Tablet, delayed release 194 mg/1 Oral RedHill Biopharma Ltd 2021-07-01 Not applicable US Aemcolo Tablet, delayed release 194 mg/1 Oral Aries Pharmaceuticals Inc 2019-02-01 2022-04-01 US Aemcolo Tablet, delayed release 194 mg/1 Oral RedHill Biopharma Ltd 2021-07-01 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image RIF 125 MG 1 AMPUL Rifamycin sodium (125 mg) + Lidocaine hydrochloride (5 mg) Solution Intramuscular KOÇAK FARMA İLAÇ VE KİMYA SAN. A.Ş. 2008-04-17 Not applicable Turkey RİF 250 MG/3 ML IM ENJEKSİYONLUK ÇÖZELTİ (1 AMPUL) Rifamycin sodium (250 mg) + Lidocaine hydrochloride (10 mg) Solution Intramuscular KOÇAK FARMA İLAÇ VE KİMYA SAN. A.Ş. 2008-04-17 Not applicable Turkey RİF 250 MG/3 ML IM ENJEKSİYONLUK ÇÖZELTİ (100 AMPUL) Rifamycin sodium (250 mg) + Lidocaine hydrochloride (10 mg) Solution Intramuscular KOÇAK FARMA İLAÇ VE KİMYA SAN. A.Ş. 2008-04-17 Not applicable Turkey RIFETEM 125 MG / 1,5 ML AMPUL, 1 ADET Rifamycin (125 mg/1.5ml) + Lidocaine hydrochloride (5 mg/1.5ml) Solution Intramuscular MENARİNİ SAĞLIK VE İLAÇ SAN. VE TİC. A.Ş. 1996-05-03 2021-03-16 Turkey RIFETEM 250 MG / 3 ML AMPUL, 1 ADET Rifamycin (250 mg/3ml) + Lidocaine hydrochloride (10 mg/3ml) Solution Intramuscular İ.E. ULAGAY İLAÇ SAN. TÜRK A.Ş. 1996-05-03 2024-01-23 Turkey
Categories
- ATC Codes
- S01AA16 — RifamycinS02AA12 — RifamycinD06AX15 — Rifamycin
- D06AX — Other antibiotics for topical use
- D06A — ANTIBIOTICS FOR TOPICAL USE
- D06 — ANTIBIOTICS AND CHEMOTHERAPEUTICS FOR DERMATOLOGICAL USE
- D — DERMATOLOGICALS
- A07AA — Antibiotics
- A07A — INTESTINAL ANTIINFECTIVES
- A07 — ANTIDIARRHEALS, INTESTINAL ANTIINFLAMMATORY/ANTIINFECTIVE AGENTS
- A — ALIMENTARY TRACT AND METABOLISM
- Drug Categories
- Alimentary Tract and Metabolism
- Anti-Bacterial Agents
- Anti-Infective Agents
- Antibiotics for Topical Use
- Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents
- Antiinfectives for Systemic Use
- Antimycobacterials
- Antirheumatic Agents
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2B6 Inducers
- Cytochrome P-450 CYP2B6 Inducers (strength unknown)
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Inducers
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2C8 Inducers
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Inducers
- Cytochrome P-450 CYP2C9 Inducers (strength unknown)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Inducers (strong)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strong)
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Dermatologicals
- Drugs for Treatment of Tuberculosis
- Heterocyclic Compounds, Fused-Ring
- Intestinal Antiinfectives
- Lactams, Macrocyclic
- MATE 1 Inhibitors
- MATE inhibitors
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- Ophthalmologicals
- Organic Anion Transporting Polypeptide 2B1 Inhibitors
- Otologicals
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Rifamycin Antibacterial
- Rifamycins
- Sensory Organs
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as macrolactams. These are cyclic amides of amino carboxylic acids, having a 1-azacycloalkan-2-one structure, or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. They are nitrogen analogues (the a nitrogen atom replacing the o atom of the cyclic carboxylic acid group ) of the naturally occurring macrolides.
- Kingdom
- Organic compounds
- Super Class
- Phenylpropanoids and polyketides
- Class
- Macrolactams
- Sub Class
- Not Available
- Direct Parent
- Macrolactams
- Alternative Parents
- Naphthofurans / Naphthols and derivatives / Benzofurans / Coumarans / Aryl alkyl ketones / Hydroquinones / 1-hydroxy-2-unsubstituted benzenoids / Ketals / Secondary carboxylic acid amides / Secondary alcohols show 11 more
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / 1-naphthol / Acetal / Alcohol / Aromatic heteropolycyclic compound / Aryl alkyl ketone / Aryl ketone / Azacycle / Benzenoid / Benzofuran show 27 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- acetate ester, polyphenol, lactam, macrocycle, cyclic ketal, rifamycin (CHEBI:29673) / Ansamycins and related polyketides (C12044) / Ansamycins and related polyketides (LMPK05000005)
- Affected organisms
- Escherichia coli
Chemical Identifiers
- UNII
- DU69T8ZZPA
- CAS number
- 6998-60-3
- InChI Key
- HJYYPODYNSCCOU-ODRIEIDWSA-N
- InChI
- InChI=1S/C37H47NO12/c1-16-11-10-12-17(2)36(46)38-23-15-24(40)26-27(32(23)44)31(43)21(6)34-28(26)35(45)37(8,50-34)48-14-13-25(47-9)18(3)33(49-22(7)39)20(5)30(42)19(4)29(16)41/h10-16,18-20,25,29-30,33,40-44H,1-9H3,(H,38,46)/b11-10+,14-13+,17-12-/t16-,18+,19+,20+,25-,29-,30+,33+,37-/m0/s1
- IUPAC Name
- (7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.1^{4,7}.0^{5,28}]triaconta-1,3,5(28),9,19,21,25(29),26-octaen-13-yl acetate
- SMILES
- CO[C@H]1\C=C\O[C@@]2(C)OC3=C(C)C(O)=C4C(O)=C(NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)C=C(O)C4=C3C2=O
References
- General References
- Lin SW, Lin CJ, Yang JC: Rifamycin SV MMX for the treatment of traveler's diarrhea. Expert Opin Pharmacother. 2017 Aug;18(12):1269-1277. doi: 10.1080/14656566.2017.1353079. Epub 2017 Jul 27. [Article]
- Sensi P: History of the development of rifampin. Rev Infect Dis. 1983 Jul-Aug;5 Suppl 3:S402-6. [Article]
- Barrett J, Brown M: Travellers' diarrhoea. BMJ. 2016 Apr 19;353:i1937. doi: 10.1136/bmj.i1937. [Article]
- Ross AG, Olds GR, Cripps AW, Farrar JJ, McManus DP: Enteropathogens and chronic illness in returning travelers. N Engl J Med. 2013 May 9;368(19):1817-25. doi: 10.1056/NEJMra1207777. [Article]
- Rosette C, Buendia-Laysa F Jr, Patkar S, Moro L, Celasco G, Bozzella R, Ajani M, Gerloni M: Anti-inflammatory and immunomodulatory activities of rifamycin SV. Int J Antimicrob Agents. 2013 Aug;42(2):182-6. doi: 10.1016/j.ijantimicag.2013.04.020. Epub 2013 Jun 5. [Article]
- Di Stefano AF, Rusca A, Loprete L, Droge MJ, Moro L, Assandri A: Systemic absorption of rifamycin SV MMX administered as modified-release tablets in healthy volunteers. Antimicrob Agents Chemother. 2011 May;55(5):2122-8. doi: 10.1128/AAC.01504-10. Epub 2011 Mar 14. [Article]
- Aristoff PA, Garcia GA, Kirchhoff PD, Showalter HD: Rifamycins--obstacles and opportunities. Tuberculosis (Edinb). 2010 Mar;90(2):94-118. doi: 10.1016/j.tube.2010.02.001. Epub 2010 Mar 16. [Article]
- Floss HG, Yu TW: Rifamycin-mode of action, resistance, and biosynthesis. Chem Rev. 2005 Feb;105(2):621-32. doi: 10.1021/cr030112j. [Article]
- Kerr P. (2013). Fighting multidrug resistance with herbal extracts, essential oils and their components. Academic Press.
- FDA approvals [Link]
- EMA approvals [Link]
- FDA news [Link]
- Bentham Science [Link]
- FDA Approved Drug Products: AEMCOLO (rifamycin) delayed-release tablets, for oral use [Link]
- External Links
- KEGG Drug
- D02549
- KEGG Compound
- C12044
- PubChem Substance
- 347911235
- ChemSpider
- 16735998
- BindingDB
- 50391000
- 35616
- ChEBI
- 29673
- ChEMBL
- CHEMBL437765
- ZINC
- ZINC000169633673
- Wikipedia
- Rifamycin
- FDA label
- Download (349 KB)
- MSDS
- Download (23.5 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 Basic Science Human Immunodeficiency Virus (HIV) Infections 1 somestatus stop reason just information to hide 4 Active Not Recruiting Prevention Impacted Third Molar Tooth 1 somestatus stop reason just information to hide 4 Recruiting Treatment Pulmonology 1 somestatus stop reason just information to hide 3 Completed Treatment Traveler's Diarrhea 2 somestatus stop reason just information to hide 3 Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) / Human Immunodeficiency Virus (HIV) Infections / Tuberculosis (TB) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, delayed release Oral 194 mg/1 Solution Intramuscular 125 mg Solution Intramuscular 250 mg Injection Intramuscular 125 mg/1.5ml Solution Topical 1 g Solution / drops Ophthalmic 1 % Solution / drops Auricular (otic) 1 % Solution Intramuscular Injection, solution Intramuscular 250 MG/3ML Injection, solution Intravenous 250 MG/10ML Injection, solution Intravenous 500 MG/10ML Injection, solution Intramuscular Solution / drops Ophthalmic 10 mg/5ml Solution / drops Auricular (otic) 100 mg/10ml Injection, solution 250 mg/3ml Tablet 200 MG - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8741948 No 2014-06-03 2025-05-03 US US8263120 No 2012-09-11 2025-05-03 US US8529945 No 2013-09-10 2025-05-03 US US8486446 No 2013-07-16 2025-05-03 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 171 ºC 'MSDS' boiling point (°C) 972.8 ºC at 760 mm Hg 'MSDS' water solubility Insoluble Shu-Wen L., Chun-Jung L. and Jyh-Chin Y. (2017). Expert Opinion in Pharmacotherapy. Vol 18. logP 5 Shu-Wen L., Chun-Jung L. and Jyh-Chin Y. (2017). Expert Opinion in Pharmacotherapy. Vol 18. pKa 1.8 Stefano A., Rusca A., Loprete L., Droge M., Moro L. and Assandri A. (2011). Antimicrob Agents Chemother. - Predicted Properties
Property Value Source Water Solubility 0.0147 mg/mL ALOGPS logP 4.15 ALOGPS logP 4.17 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 7.09 Chemaxon pKa (Strongest Basic) -1.1 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 11 Chemaxon Hydrogen Donor Count 6 Chemaxon Polar Surface Area 201.31 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 187.8 m3·mol-1 Chemaxon Polarizability 72.6 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 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]- 264.6304243 predictedDarkChem Lite v0.1.0 [M-H]- 261.33533 predictedDeepCCS 1.0 (2019) [M+H]+ 264.5424243 predictedDarkChem Lite v0.1.0 [M+H]+ 263.17422 predictedDeepCCS 1.0 (2019) [M+Na]+ 264.1724243 predictedDarkChem Lite v0.1.0 [M+Na]+ 269.3163 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
- Specific Function
- DNA binding
- Gene Name
- rpoB
- Uniprot ID
- P9WGY9
- Uniprot Name
- DNA-directed RNA polymerase subunit beta
- Molecular Weight
- 129863.895 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
- Mycobacterium tuberculosis
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
- Specific Function
- DNA binding
- Gene Name
- rpoC
- Uniprot ID
- P9WGY7
- Uniprot Name
- DNA-directed RNA polymerase subunit beta'
- Molecular Weight
- 146768.085 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
- Binder
- General Function
- DNA-dependent RNA polymerase (RNAP) catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
- Specific Function
- DNA binding
- Gene Name
- rpoB
- Uniprot ID
- P0A8V2
- Uniprot Name
- DNA-directed RNA polymerase subunit beta
- Molecular Weight
- 150631.165 Da
References
- Floss HG, Yu TW: Rifamycin-mode of action, resistance, and biosynthesis. Chem Rev. 2005 Feb;105(2):621-32. doi: 10.1021/cr030112j. [Article]
- Kind
- Protein
- Organism
- Escherichia coli (strain K12)
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- DNA-dependent RNA polymerase (RNAP) catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. This subunit plays an important role in subunit assembly since its dimerization is the first step in the sequential assembly of subunits to form the holoenzyme.
- Specific Function
- DNA binding
- Gene Name
- rpoA
- Uniprot ID
- P0A7Z4
- Uniprot Name
- DNA-directed RNA polymerase subunit alpha
- Molecular Weight
- 36511.35 Da
References
- Floss HG, Yu TW: Rifamycin-mode of action, resistance, and biosynthesis. Chem Rev. 2005 Feb;105(2):621-32. doi: 10.1021/cr030112j. [Article]
- Kind
- Protein
- Organism
- Escherichia coli (strain K12)
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- DNA-dependent RNA polymerase (RNAP) catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
- Specific Function
- DNA binding
- Gene Name
- rpoC
- Uniprot ID
- P0A8T7
- Uniprot Name
- DNA-directed RNA polymerase subunit beta'
- Molecular Weight
- 155158.84 Da
References
- Floss HG, Yu TW: Rifamycin-mode of action, resistance, and biosynthesis. Chem Rev. 2005 Feb;105(2):621-32. doi: 10.1021/cr030112j. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- InhibitorInducer
- 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
- Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- Pea F, Furlanut M: Pharmacokinetic aspects of treating infections in the intensive care unit: focus on drug interactions. Clin Pharmacokinet. 2001;40(11):833-68. doi: 10.2165/00003088-200140110-00004. [Article]
- Edwards RJ, Price RJ, Watts PS, Renwick AB, Tredger JM, Boobis AR, Lake BG: Induction of cytochrome P450 enzymes in cultured precision-cut human liver slices. Drug Metab Dispos. 2003 Mar;31(3):282-8. [Article]
- Ridtitid W, Wongnawa M, Mahatthanatrakul W, Punyo J, Sunbhanich M: Rifampin markedly decreases plasma concentrations of praziquantel in healthy volunteers. Clin Pharmacol Ther. 2002 Nov;72(5):505-13. doi: 10.1067/mcp.2002.129319. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- InhibitorInducer
- 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
- Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). 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:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- InhibitorInducer
- Curator comments
- Rifamycin derivatives are inducers of CYP2C9 hepatic enzyme. This enzyme action is based on the drug class of Rifamycin.
- 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
- Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
- Chen Y, Ferguson SS, Negishi M, Goldstein JA: Induction of human CYP2C9 by rifampicin, hyperforin, and phenobarbital is mediated by the pregnane X receptor. J Pharmacol Exp Ther. 2004 Feb;308(2):495-501. Epub 2003 Nov 4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- Di Stefano AF, Rusca A, Loprete L, Droge MJ, Moro L, Assandri A: Systemic absorption of rifamycin SV MMX administered as modified-release tablets in healthy volunteers. Antimicrob Agents Chemother. 2011 May;55(5):2122-8. doi: 10.1128/AAC.01504-10. Epub 2011 Mar 14. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Na(+)-independent transporter that mediates the cellular uptake of a broad range of organic anions such as the endogenous bile salts cholate and deoxycholate, either in their unconjugated or conjugated forms (taurocholate and glycocholate), at the plasmam membrane (PubMed:19129463, PubMed:7557095). Responsible for intestinal absorption of bile acids (By similarity). Transports dehydroepiandrosterone 3-sulfate (DHEAS), a major circulating steroid secreted by the adrenal cortex, as well as estrone 3-sulfate and 17beta-estradiol 17-O-(beta-D-glucuronate) (PubMed:11159893, PubMed:12568656, PubMed:19129463, PubMed:23918469, PubMed:25560245, PubMed:9539145). Mediates apical uptake of all-trans-retinol (atROL) across human retinal pigment epithelium, which is essential to maintaining the integrity of the visual cycle and thus vision (PubMed:25560245). Involved in the uptake of clinically used drugs (PubMed:17301733, PubMed:20686826, PubMed:27777271). Capable of thyroid hormone transport (both T3 or 3,3',5'-triiodo-L-thyronine, and T4 or L-tyroxine) (PubMed:19129463, PubMed:20358049). Also transports prostaglandin E2 (PubMed:19129463). Plays roles in blood-brain and -cerebrospinal fluid barrier transport of organic anions and signal mediators, and in hormone uptake by neural cells (By similarity). May also play a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). Shows a pH-sensitive substrate specificity 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). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1A2
- Uniprot ID
- P46721
- Uniprot Name
- Solute carrier organic anion transporter family member 1A2
- Molecular Weight
- 74144.105 Da
References
- Hirano M, Maeda K, Shitara Y, Sugiyama Y: Drug-drug interaction between pitavastatin and various drugs via OATP1B1. Drug Metab Dispos. 2006 Jul;34(7):1229-36. doi: 10.1124/dmd.106.009290. Epub 2006 Apr 4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- Hirano M, Maeda K, Shitara Y, Sugiyama Y: Drug-drug interaction between pitavastatin and various drugs via OATP1B1. Drug Metab Dispos. 2006 Jul;34(7):1229-36. doi: 10.1124/dmd.106.009290. Epub 2006 Apr 4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- Hirano M, Maeda K, Shitara Y, Sugiyama Y: Drug-drug interaction between pitavastatin and various drugs via OATP1B1. Drug Metab Dispos. 2006 Jul;34(7):1229-36. doi: 10.1124/dmd.106.009290. Epub 2006 Apr 4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Mediates the transport of prostaglandins (PGs, mainly PGE2, PGE1, PGE3, PGF2alpha, PGD2, PGH2) and thromboxanes (thromboxane B2) across the cell membrane (PubMed:11997326, PubMed:26692285, PubMed:8787677). PGs and thromboxanes play fundamental roles in diverse functions such as intraocular pressure, gastric acid secretion, renal salt and water transport, vascular tone, and fever (PubMed:15044627). Plays a role in the clearance of PGs from the circulation through cellular uptake, which allows cytoplasmic oxidation and PG signal termination (PubMed:8787677). PG uptake is dependent upon membrane potential and involves exchange of a monovalent anionic substrate (PGs exist physiologically as an anionic monovalent form) with a stoichiometry of 1:1 for divalent anions or of 1:2 for monovalent anions (PubMed:29204966). Uses lactate, generated by glycolysis, as a counter-substrate to mediate PGE2 influx and efflux (PubMed:11997326). Under nonglycolytic conditions, metabolites other than lactate might serve as counter-substrates (PubMed:11997326). Although the mechanism is not clear, this transporter can function in bidirectional mode (PubMed:29204966). When apically expressed in epithelial cells, it facilitates transcellular transport (also called vectorial release), extracting PG from the apical medium and facilitating transport across the cell toward the basolateral side, whereupon the PG exits the cell by simple diffusion (By similarity). In the renal collecting duct, regulates renal Na+ balance by removing PGE2 from apical medium (PGE2 EP4 receptor is likely localized to the luminal/apical membrane and stimulates Na+ resorption) and transporting it toward the basolateral membrane (where PGE2 EP1 and EP3 receptors inhibit Na+ resorption) (By similarity). Plays a role in endometrium during decidualization, increasing uptake of PGs by decidual cells (PubMed:16339169). Involved in critical events for ovulation (PubMed:27169804). Regulates extracellular PGE2 concentration for follicular development in the ovaries (By similarity). Expressed intracellularly, may contribute to vesicular uptake of newly synthesized intracellular PGs, thereby facilitating exocytotic secretion of PGs without being metabolized (By similarity). Essential core component of the major type of large-conductance anion channel, Maxi-Cl, which plays essential roles in inorganic anion transport, cell volume regulation and release of ATP and glutamate not only in physiological processes but also in pathological processes (By similarity). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
- Specific Function
- lipid transporter activity
- Gene Name
- SLCO2A1
- Uniprot ID
- Q92959
- Uniprot Name
- Solute carrier organic anion transporter family member 2A1
- Molecular Weight
- 70043.33 Da
References
- Hirano M, Maeda K, Shitara Y, Sugiyama Y: Drug-drug interaction between pitavastatin and various drugs via OATP1B1. Drug Metab Dispos. 2006 Jul;34(7):1229-36. doi: 10.1124/dmd.106.009290. Epub 2006 Apr 4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent transport of steroid sulfate conjugates and other specific organic anions (PubMed:10873595, PubMed:11159893, PubMed:11932330, PubMed:12724351, PubMed:14610227, PubMed:16908597, PubMed:18501590, PubMed:20507927, PubMed:22201122, PubMed:23531488, PubMed:25132355, PubMed:26383540, PubMed:27576593, PubMed:28408210, PubMed:29871943, PubMed:34628357). Responsible for the transport of estrone 3-sulfate (E1S) through the basal membrane of syncytiotrophoblast, highlighting a potential role in the placental absorption of fetal-derived sulfated steroids including the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S) (PubMed:11932330, PubMed:12409283). Also facilitates the uptake of sulfated steroids at the basal/sinusoidal membrane of hepatocytes, therefore accounting for the major part of organic anions clearance of liver (PubMed:11159893). Mediates the intestinal uptake of sulfated steroids (PubMed:12724351, PubMed:28408210). Mediates the uptake of the neurosteroids DHEA-S and pregnenolone sulfate (PregS) into the endothelial cells of the blood-brain barrier as the first step to enter the brain (PubMed:16908597, PubMed:25132355). Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May act as a heme transporter that promotes cellular iron availability via heme oxygenase/HMOX2 and independently of TFRC (PubMed:35714613). Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition (PubMed:26383540). Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 (PubMed:10873595, PubMed:14610227, PubMed:19129463, PubMed:29871943, Ref.25). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable). Shows a pH-sensitive substrate specificity 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:14610227, PubMed:19129463, PubMed:22201122). The exact transport mechanism has not been yet deciphered but most likely involves an anion exchange, coupling the cellular uptake of organic substrate with the efflux of an anionic compound (PubMed:19129463, PubMed:20507927, PubMed:26277985). Hydrogencarbonate/HCO3(-) acts as a probable counteranion that exchanges for organic anions (PubMed:19129463). Cytoplasmic glutamate may also act as counteranion in the placenta (PubMed:26277985). An inwardly directed proton gradient has also been proposed as the driving force of E1S uptake with a (H(+):E1S) stoichiometry of (1:1) (PubMed:20507927)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO2B1
- Uniprot ID
- O94956
- Uniprot Name
- Solute carrier organic anion transporter family member 2B1
- Molecular Weight
- 76697.93 Da
References
- Hirano M, Maeda K, Shitara Y, Sugiyama Y: Drug-drug interaction between pitavastatin and various drugs via OATP1B1. Drug Metab Dispos. 2006 Jul;34(7):1229-36. doi: 10.1124/dmd.106.009290. Epub 2006 Apr 4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- 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
- Hirano M, Maeda K, Shitara Y, Sugiyama Y: Drug-drug interaction between pitavastatin and various drugs via OATP1B1. Drug Metab Dispos. 2006 Jul;34(7):1229-36. doi: 10.1124/dmd.106.009290. Epub 2006 Apr 4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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: AEMCOLO (rifamycin) delayed-release tablets, for oral use [Link]
Drug created at October 20, 2016 20:45 / Updated at August 26, 2024 19:24