Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Nafamostat
- DrugBank Accession Number
- DB12598
- Background
Nafamostat is a synthetic serine protease inhibitor that is commonly formulated with hydrochloric acid due to its basic properties. It has been used in trials studying the prevention of Liver Transplantation and Postreperfusion Syndrome. The use of nafamostat in Asian countries is approved as an anticoagulant therapy for patients undergoing continuous renal replacement therapy due to acute kidney injury.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Nafamostat (DB12598)
- Weight
- Average: 347.378
Monoisotopic: 347.138224807 - Chemical Formula
- C19H17N5O2
- Synonyms
- Nafamostat
- Nafamostatum
- p-Guanidinobenzoic acid ester with 6-hydroxy-2-naphthamidine
Pharmacology
- Indication
Used as an anticoagulant in patients with disseminative blood vessel coagulation, hemorrhagic lesions, and hemorrhagic tendencies. It prevents blood clot formation during extracorporeal circulation in patients undergoing continuous renal replacement therapy and extra corporeal membrane oxygenation.
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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
Nafamostat is a fast-acting proteolytic inhibitor used during hemodialysis to prevent the proteolysis of fibrinogen into fibrin by competitively inhibiting several serine proteases including thrombin. It improves acute pancreatitis and prevents blood clot formation during extracorporeal circulation and has an anti-inflammatory effect in vitro. A study suggets that nafamostat has a neuroprotective role during ischemia-induced brain injury from antithrombin activity 5.
- Mechanism of action
Nafamostat mesilate inhibits various enzyme systems, such as coagulation and fibrinolytic systems (thrombin, Xa, and XIIa), the kallikrein–kinin system, the complement system, pancreatic proteases and activation of protease-activated receptors (PARs) 6. Nafamostat inhibits lipopolysaccharide-induced nitric oxide production, apoptosis, and interleukin (IL)-6 and IL-8 levels in cultured human trophoblasts. It is shown to act as an antioxidant in TNF-α-induced ROS production 2.
Target Actions Organism ATumor necrosis factor other/unknownHumans AProthrombin inhibitorHumans ACoagulation factor X inhibitorHumans ACoagulation factor XII inhibitorHumans ASerine protease 1 inhibitorHumans AKallikrein-1 inhibitorHumans UIntercellular adhesion molecule 1 inhibitorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Nafamostat is mainly hydrolyzed by hepatic carboxyesterase and long-chain acyl-CoA hydrolase in human liver cytosol. Main metabolites are p-guanidinobenzoic acid (PGBA) and 6-amidino-2-naphthol (AN) as inactive protease inhibitors.
- Route of elimination
Two metabolites of NM, p-guanidinobenzoic acid (PGBA) and 6-amidino-2-naphthol (AN), are renally excreted. Nafamostat accumulates in the kidneys.
- Half-life
Approximately 8 minutes 4
- Clearance
Not Available
- Adverse Effects
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Reported incidences of agranulocytosis, hyperkalemia, and anaphylaxis. The use of nafamostat has been reported to cause cardiac arrest in patients receiving dialysis due to a sudden change in the patient's condition such as dyspnea. A study suggests that the drug and its metabolites may inhibit the amiloride-sensitive sodium (Na) conductance at the collecting ducts, resulting in an inhibition of K secretion and hyperkalemia 7. Reported LD50 value from intravenous administration in rats is 16.4mg/kg.
- 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 softwareAbciximab The risk or severity of bleeding can be increased when Abciximab is combined with Nafamostat. Aceclofenac The risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Nafamostat. Acemetacin The risk or severity of bleeding and hemorrhage can be increased when Nafamostat is combined with Acemetacin. Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with Nafamostat. Acetylsalicylic acid Acetylsalicylic acid may increase the anticoagulant activities of Nafamostat. - Food Interactions
- Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
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 Nafamostat mesylate 1D2T74921W 82956-11-4 SRXKIZXIRHMPFW-UHFFFAOYSA-N - International/Other Brands
- Berabu (Tobishi Pharmaceutical, Japan) / Buipel (Teva Seiyaku, Japan) / Buseron (Sawai Seiyaku, Japan) / Coahibitor (AY Pharma, Japan) / Famoset (Towa Yakuhin, Japan) / Futhan (Torii Yakuhin, Japan) / Nafaston (Fuji Seiyaku, Japan) / Nafatat (Nichi-Iko Pharmaceutical, Japan) / Namostatt (Pola Pharma, Japan) / Naotamin (Asahi Kasei Pharma, Japan) / Opsun (Sanwa Kagaku, Japan) / Pathron (Nipro, Japan) / Ronastat (Koa Isei, Japan)
Categories
- Drug Categories
- Amidines
- Analgesics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Anticoagulants
- Antirheumatic Agents
- Complement Inactivating Agents
- Enzyme Inhibitors
- Fibrinolysin, antagonists & inhibitors
- Hematologic Agents
- Immunologic Factors
- Kallikreins, antagonists & inhibitors
- OCT1 substrates
- OCT2 Substrates
- Peripheral Nervous System Agents
- Protease Inhibitors
- Sensory System Agents
- Serine Protease Inhibitors
- Trypsin Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as guanidinobenzoic acids and derivatives. These are aromatic compounds containing a guanidine group linked to the benzene ring of a benzoic acid (or a derivative thereof).
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Benzoic acids and derivatives
- Direct Parent
- Guanidinobenzoic acids and derivatives
- Alternative Parents
- Naphthalenes / Benzoic acid esters / Benzoyl derivatives / Guanidines / Carboxylic acid esters / Propargyl-type 1,3-dipolar organic compounds / Monocarboxylic acids and derivatives / Carboximidamides / Carboxamidines / Organopnictogen compounds show 3 more
- Substituents
- Amidine / Aromatic homopolycyclic compound / Benzoate ester / Benzoyl / Carboximidamide / Carboxylic acid amidine / Carboxylic acid derivative / Carboxylic acid ester / Guanidine / Guanidinobenzoic acid or derivatives show 11 more
- Molecular Framework
- Aromatic homopolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- Y25LQ0H97D
- CAS number
- 81525-10-2
- InChI Key
- MQQNFDZXWVTQEH-UHFFFAOYSA-N
- InChI
- InChI=1S/C19H17N5O2/c20-17(21)14-2-1-13-10-16(8-5-12(13)9-14)26-18(25)11-3-6-15(7-4-11)24-19(22)23/h1-10H,(H3,20,21)(H4,22,23,24)
- IUPAC Name
- 6-carbamimidoylnaphthalen-2-yl 4-carbamimidamidobenzoate
- SMILES
- NC(=N)NC1=CC=C(C=C1)C(=O)OC1=CC2=C(C=C1)C=C(C=C2)C(N)=N
References
- General References
- Maruyama Y, Yoshida H, Uchino S, Yokoyama K, Yamamoto H, Takinami M, Hosoya T: Nafamostat mesilate as an anticoagulant during continuous veno-venous hemodialysis: a three-year retrospective cohort study. Int J Artif Organs. 2011 Jul;34(7):571-6. doi: 10.5301/IJAO.2011.8535. [Article]
- Kang MW, Song HJ, Kang SK, Kim Y, Jung SB, Jee S, Moon JY, Suh KS, Lee SD, Jeon BH, Kim CS: Nafamostat Mesilate Inhibits TNF-alpha-Induced Vascular Endothelial Cell Dysfunction by Inhibiting Reactive Oxygen Species Production. Korean J Physiol Pharmacol. 2015 May;19(3):229-34. doi: 10.4196/kjpp.2015.19.3.229. Epub 2015 Apr 30. [Article]
- Choi S, Kwon HJ, Song HJ, Choi SW, Nagar H, Piao S, Jung SB, Jeon BH, Kim DW, Kim CS: Nafamostat mesilate promotes endothelium-dependent vasorelaxation via the Akt-eNOS dependent pathway. Korean J Physiol Pharmacol. 2016 Sep;20(5):539-45. doi: 10.4196/kjpp.2016.20.5.539. Epub 2016 Aug 26. [Article]
- Choi JY, Kang YJ, Jang HM, Jung HY, Cho JH, Park SH, Kim YL, Kim CD: Nafamostat Mesilate as an Anticoagulant During Continuous Renal Replacement Therapy in Patients With High Bleeding Risk: A Randomized Clinical Trial. Medicine (Baltimore). 2015 Dec;94(52):e2392. doi: 10.1097/MD.0000000000002392. [Article]
- Chen T, Wang J, Li C, Zhang W, Zhang L, An L, Pang T, Shi X, Liao H: Nafamostat mesilate attenuates neuronal damage in a rat model of transient focal cerebral ischemia through thrombin inhibition. Sci Rep. 2014 Jul 2;4:5531. doi: 10.1038/srep05531. [Article]
- Kim HS, Lee KE, Oh JH, Jung CS, Choi D, Kim Y, Jeon JS, Han DC, Noh H: Cardiac arrest caused by nafamostat mesilate. Kidney Res Clin Pract. 2016 Sep;35(3):187-9. doi: 10.1016/j.krcp.2015.10.003. Epub 2015 Nov 12. [Article]
- Muto S, Imai M, Asano Y: Mechanisms of the hyperkalaemia caused by nafamostat mesilate: effects of its two metabolites on Na+ and K+ transport properties in the rabbit cortical collecting duct. Br J Pharmacol. 1994 Jan;111(1):173-8. [Article]
- FDA Executive Summary [Link]
- External Links
- PubChem Compound
- 4413
- PubChem Substance
- 347828816
- ChemSpider
- 4260
- BindingDB
- 50063698
- ChEBI
- 135466
- ChEMBL
- CHEMBL273264
- ZINC
- ZINC000003874467
- PDBe Ligand
- 7RF
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Nafamostat
- PDB Entries
- 7vm7
- MSDS
- Download (29.4 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 Not Yet Recruiting Other Extracorporeal Membrane Oxygenation Complication 1 somestatus stop reason just information to hide Not Available Recruiting Prevention Bleeding / Dialysis; Complications 1 somestatus stop reason just information to hide 4 Completed Prevention Liver Transplantation / Postreperfusion Syndrome 1 somestatus stop reason just information to hide 4 Completed Treatment Acute Kidney Injury (AKI) 2 somestatus stop reason just information to hide 4 Not Yet Recruiting Treatment Nafamostat Mesilate / Sepsis / Sepsis-induced Coagulopathy 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0341 mg/mL ALOGPS logP 1.91 ALOGPS logP 2.52 Chemaxon logS -4 ALOGPS pKa (Strongest Basic) 11.32 Chemaxon Physiological Charge 2 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 5 Chemaxon Polar Surface Area 138.07 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 122.12 m3·mol-1 Chemaxon Polarizability 36.48 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes 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 splash10-03di-0900000000-ca2f2f9e08a54703578e Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-000t-0009000000-6eb33cc8cd7cb4de16bc Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0udj-0029000000-0a623f58ae16e62cdaa0 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0udi-2009000000-1a18391888c237755247 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-001r-0389000000-d63054a46b1c892023dc Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-9031000000-9193a082f90abfc29b48 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-1900000000-f2cfae87f4a152e0e2ca 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]- 203.8852765 predictedDarkChem Lite v0.1.0 [M-H]- 177.02306 predictedDeepCCS 1.0 (2019) [M+H]+ 203.8004765 predictedDarkChem Lite v0.1.0 [M+H]+ 179.38106 predictedDeepCCS 1.0 (2019) [M+Na]+ 203.0080765 predictedDarkChem Lite v0.1.0 [M+Na]+ 186.38634 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Other/unknown
- General Function
- Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Up-regulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line (PubMed:16829952, PubMed:22517918, PubMed:23396208). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity). Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6 (PubMed:12794819). Promotes osteoclastogenesis and therefore mediates bone resorption (By similarity)
- Specific Function
- cytokine activity
- Gene Name
- TNF
- Uniprot ID
- P01375
- Uniprot Name
- Tumor necrosis factor
- Molecular Weight
- 25644.15 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
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing. Thrombin triggers the production of pro-inflammatory cytokines, such as MCP-1/CCL2 and IL8/CXCL8, in endothelial cells (PubMed:30568593, PubMed:9780208)
- Specific Function
- calcium ion binding
- Gene Name
- F2
- Uniprot ID
- P00734
- Uniprot Name
- Prothrombin
- Molecular Weight
- 70036.295 Da
References
- Iwaki M, Ino Y, Motoyoshi A, Ozeki M, Sato T, Kurumi M, Aoyama T: Pharmacological studies of FUT-175, nafamostat mesilate. V. Effects on the pancreatic enzymes and experimental acute pancreatitis in rats. Jpn J Pharmacol. 1986 Jun;41(2):155-62. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting. Factor Xa activates pro-inflammatory signaling pathways in a protease-activated receptor (PAR)-dependent manner (PubMed:24041930, PubMed:30568593, PubMed:34831181). Up-regulates expression of protease-activated receptors (PARs) F2R, F2RL1 and F2RL2 in dermal microvascular endothelial cells (PubMed:35738824). Triggers the production of pro-inflammatory cytokines, such as MCP-1/CCL2 and IL6, in cardiac fibroblasts and umbilical vein endothelial cells in PAR-1 (F2R)-dependent manner (PubMed:30568593, PubMed:34831181). Triggers the production of pro-inflammatory cytokines, such as MCP-1/CCL2, IL6, TNF-alpha/TNF, IL-1beta/IL1B, IL8/CXCL8 and IL18, in endothelial cells and atrial tissues (PubMed:24041930, PubMed:35738824, PubMed:9780208). Induces expression of adhesion molecules, such as ICAM1, VCAM1 and SELE, in endothelial cells and atrial tissues (PubMed:24041930, PubMed:35738824, PubMed:9780208). Increases expression of phosphorylated ERK1/2 in dermal microvascular endothelial cells and atrial tissues (PubMed:24041930, PubMed:35738824). Triggers activation of the transcription factor NF-kappa-B in dermal microvascular endothelial cells and atrial tissues (PubMed:24041930, PubMed:35738824). Up-regulates expression of plasminogen activator inhibitor 1 (SERPINE1) in atrial tissues (PubMed:24041930)
- Specific Function
- calcium ion binding
- Gene Name
- F10
- Uniprot ID
- P00742
- Uniprot Name
- Coagulation factor X
- Molecular Weight
- 54731.255 Da
References
- Baek NN, Jang HR, Huh W, Kim YG, Kim DJ, Oh HY, Lee JE: The role of nafamostat mesylate in continuous renal replacement therapy among patients at high risk of bleeding. Ren Fail. 2012;34(3):279-85. doi: 10.3109/0886022X.2011.647293. Epub 2012 Jan 17. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Factor XII is a serum glycoprotein that participates in the initiation of blood coagulation, fibrinolysis, and the generation of bradykinin and angiotensin. Prekallikrein is cleaved by factor XII to form kallikrein, which then cleaves factor XII first to alpha-factor XIIa and then trypsin cleaves it to beta-factor XIIa. Alpha-factor XIIa activates factor XI to factor XIa
- Specific Function
- calcium ion binding
- Gene Name
- F12
- Uniprot ID
- P00748
- Uniprot Name
- Coagulation factor XII
- Molecular Weight
- 67791.53 Da
References
- Baek NN, Jang HR, Huh W, Kim YG, Kim DJ, Oh HY, Lee JE: The role of nafamostat mesylate in continuous renal replacement therapy among patients at high risk of bleeding. Ren Fail. 2012;34(3):279-85. doi: 10.3109/0886022X.2011.647293. Epub 2012 Jan 17. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Has activity against the synthetic substrates Boc-Phe-Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val-Pro-Arg-Mec. The single-chain form is more active than the two-chain form against all of these substrates
- Specific Function
- metal ion binding
- Gene Name
- PRSS1
- Uniprot ID
- P07477
- Uniprot Name
- Serine protease 1
- Molecular Weight
- 26557.88 Da
References
- Ramjee MK, Henderson IM, McLoughlin SB, Padova A: The kinetic and structural characterization of the reaction of nafamostat with bovine pancreatic trypsin. Thromb Res. 2000 Jun 15;98(6):559-69. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin
- Specific Function
- serine-type endopeptidase activity
- Gene Name
- KLK1
- Uniprot ID
- P06870
- Uniprot Name
- Kallikrein-1
- Molecular Weight
- 28889.425 Da
References
- Iwaki M, Ino Y, Motoyoshi A, Ozeki M, Sato T, Kurumi M, Aoyama T: Pharmacological studies of FUT-175, nafamostat mesilate. V. Effects on the pancreatic enzymes and experimental acute pancreatitis in rats. Jpn J Pharmacol. 1986 Jun;41(2):155-62. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical cups through ARHGEF26/SGEF and RHOG activation
- Specific Function
- integrin binding
- Gene Name
- ICAM1
- Uniprot ID
- P05362
- Uniprot Name
- Intercellular adhesion molecule 1
- Molecular Weight
- 57824.785 Da
References
- Kang MW, Song HJ, Kang SK, Kim Y, Jung SB, Jee S, Moon JY, Suh KS, Lee SD, Jeon BH, Kim CS: Nafamostat Mesilate Inhibits TNF-alpha-Induced Vascular Endothelial Cell Dysfunction by Inhibiting Reactive Oxygen Species Production. Korean J Physiol Pharmacol. 2015 May;19(3):229-34. doi: 10.4196/kjpp.2015.19.3.229. Epub 2015 Apr 30. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:11388889, PubMed:11408531, PubMed:12439218, PubMed:12719534, PubMed:15389554, PubMed:16263091, PubMed:16272756, PubMed:16581093, PubMed:19536068, PubMed:21128598, PubMed:23680637, PubMed:24961373, PubMed:34040533, PubMed:9187257, PubMed:9260930, PubMed:9655880). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation (PubMed:16263091). Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline (PubMed:12439218, PubMed:24961373, PubMed:35469921, PubMed:9260930). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover (PubMed:21128598). Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism (PubMed:24961373). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency (PubMed:17460754). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (Probable). Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:11408531, PubMed:15389554, PubMed:35469921, PubMed:9260930)
- Specific Function
- (R)-carnitine transmembrane transporter activity
- Gene Name
- SLC22A1
- Uniprot ID
- O15245
- Uniprot Name
- Solute carrier family 22 member 1
- Molecular Weight
- 61153.345 Da
References
- Li Q, Sai Y, Kato Y, Muraoka H, Tamai I, Tsuji A: Transporter-mediated renal handling of nafamostat mesilate. J Pharm Sci. 2004 Feb;93(2):262-72. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:9260930, PubMed:9687576). Functions as a Na(+)-independent, bidirectional uniporter (PubMed:21128598, PubMed:9687576). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:15212162, PubMed:9260930, PubMed:9687576). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (PubMed:15783073). Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters (PubMed:16581093, PubMed:17460754, PubMed:9687576). Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system (PubMed:17460754). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) (PubMed:12089365, PubMed:15212162, PubMed:17072098, PubMed:24961373, PubMed:9260930). Mediates the uptake and efflux of quaternary ammonium compound choline (PubMed:9260930). Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:12538837, PubMed:21128598). Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:12395288, PubMed:16394027). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
- Specific Function
- acetylcholine transmembrane transporter activity
- Gene Name
- SLC22A2
- Uniprot ID
- O15244
- Uniprot Name
- Solute carrier family 22 member 2
- Molecular Weight
- 62579.99 Da
References
- Li Q, Sai Y, Kato Y, Muraoka H, Tamai I, Tsuji A: Transporter-mediated renal handling of nafamostat mesilate. J Pharm Sci. 2004 Feb;93(2):262-72. [Article]
Drug created at October 20, 2016 23:07 / Updated at August 26, 2024 19:23