Tmic
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Record Information
Version2.0
Creation Date2009-07-21 20:27:55 UTC
Update Date2014-12-24 20:25:53 UTC
Accession NumberT3D2925
Identification
Common NameOndansetron
ClassSmall Molecule
DescriptionOndansetron is a well tolerated drug with few side effects. Headache, constipation, and dizziness are the most commonly reported side effects associated with its use. There have been no significant drug interactions reported with this drugs use. It is broken down by the hepatic cytochrome P450 system and it has little effect on the metabolism of other drugs broken down by this system; Ondansetron is a serotonin 5-HT3 receptor antagonist used mainly to treat nausea and vomiting following chemotherapy. Its effects are thought to be on both peripheral and central nerves. One part is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata, the other is a blockage of serotonin receptors in the chemoreceptor trigger zone. It does not have much effect on vomiting due to motion sickness. This drug does not have any effect on dopamine receptors or muscarinic receptors; A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and has reported anxiolytic and neuroleptic properties; Ondansetron (INN) is a serotonin 5-HT3 receptor antagonist used mainly to treat nausea and vomiting following chemotherapy. Its effects are thought to be on both peripheral and central nerves. One part is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata, the other is a blockage of serotonin receptors in the chemoreceptor trigger zone. It does not have much effect on vomiting due to motion sickness. This drug does not have any effect on dopamine receptors or muscarinic receptors.
Compound Type
  • Amide
  • Amine
  • Anti-Anxiety Agent
  • Antiemetic
  • Antipruritic
  • Antipsychotic Agent
  • Drug
  • Ester
  • Food Toxin
  • Metabolite
  • Organic Compound
  • Serotonin Antagonist
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Zofran
Zofran odt
Zophren
Zudan
Zuplenz
Chemical FormulaC18H19N3O
Average Molecular Mass293.363 g/mol
Monoisotopic Mass293.153 g/mol
CAS Registry Number99614-02-5
IUPAC Name9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-2,3,4,9-tetrahydro-1H-carbazol-4-one
Traditional Nameondansetron
SMILESCN1C2=C(C3=CC=CC=C13)C(=O)C(CN1C=CN=C1C)CC2
InChI IdentifierInChI=1/C18H19N3O/c1-12-19-9-10-21(12)11-13-7-8-16-17(18(13)22)14-5-3-4-6-15(14)20(16)2/h3-6,9-10,13H,7-8,11H2,1-2H3
InChI KeyInChIKey=FELGMEQIXOGIFQ-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as carbazoles. Carbazoles are compounds containing a three ring system containing a pyrrole ring fused on either side to a benzene ring.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIndoles and derivatives
Sub ClassCarbazoles
Direct ParentCarbazoles
Alternative Parents
Substituents
  • Carbazole
  • N-alkylindole
  • Indole
  • Aryl ketone
  • Aryl alkyl ketone
  • N-methylpyrrole
  • N-substituted imidazole
  • Substituted pyrrole
  • Benzenoid
  • Imidazole
  • Pyrrole
  • Azole
  • Vinylogous amide
  • Heteroaromatic compound
  • Ketone
  • Azacycle
  • Organic oxide
  • Organopnictogen compound
  • Organic nitrogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Liver
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point231 - 232°C
Boiling PointNot Available
SolubilityNot Available
LogP2.4
Predicted Properties
PropertyValueSource
Water Solubility0.25 g/LALOGPS
logP2.56ALOGPS
logP2.35ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)15.39ChemAxon
pKa (Strongest Basic)7.34ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area39.82 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity86.78 m³·mol⁻¹ChemAxon
Polarizability33.16 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00nb-9840000000-3e06f3c6b7dfe3741b9dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0006-0590000000-1c293e5af06aedfb74e1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-006x-0790000000-39dfc83ad8c54c21d83dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-0090000000-cd5ee2ea8a09e479ca82View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03dl-1190000000-b8299468585346441088View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001r-7930000000-39cdbd8680e338fc52d1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-3090000000-6ea6246fc080e90b47b9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-9040000000-063a9351d8828458eb6aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-67ae58fff567a97b5c75View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureOndansetron is well absorbed after oral administration and undergoes limited first-pass metabolism.
Mechanism of ToxicityOndansetron is a selective serotonin 5-HT3 receptor antagonist. The antiemetic activity of the drug is brought about through the inhibition of 5-HT3 receptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of 5-HT3 receptors in turn inhibits the visceral afferent stimulation of the vomiting center, likely indirectly at the level of the area postrema, as well as through direct inhibition of serotonin activity within the area postrema and the chemoreceptor trigger zone.
MetabolismHepatic Half Life: 5.7 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy, postoperation, and radiation. Also used for the treatment of postoperative nausea and vomiting.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsLow blood pressure and fainting, sudden blindness, severe constipation
TreatmentThere is no specific antidote for ondansetron overdose. Patients should be managed with appropriate supportive therapy. (8)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00904
HMDB IDHMDB05035
PubChem Compound ID4595
ChEMBL IDCHEMBL46
ChemSpider ID4434
KEGG IDC07325
UniProt IDNot Available
OMIM ID
ChEBI ID103183
BioCyc IDNot Available
CTD IDNot Available
Stitch IDOndansetron
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkOndansetron
References
Synthesis Reference

Peter Bod, Kalman Harsanyi, Ferenc Trischler, Eva Fekecs, Attila Csehi, Bela Hegedus, Eva Mersich nee Donat, Gyorgyi Szabo nee Komlosi, Erika Horvath nee Sziki, “Process for preparing ondansetron.” U.S. Patent US5478949, issued September, 1990.

MSDSLink
General References
  1. Ramsook C, Sahagun-Carreon I, Kozinetz CA, Moro-Sutherland D: A randomized clinical trial comparing oral ondansetron with placebo in children with vomiting from acute gastroenteritis. Ann Emerg Med. 2002 Apr;39(4):397-403. [11919526 ]
  2. Yilmaz HL, Yildizdas RD, Sertdemir Y: Clinical trial: oral ondansetron for reducing vomiting secondary to acute gastroenteritis in children--a double-blind randomized study. Aliment Pharmacol Ther. 2010 Jan;31(1):82-91. doi: 10.1111/j.1365-2036.2009.04145.x. Epub . [19758398 ]
  3. Gregory RE, Ettinger DS: 5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting. A comparison of their pharmacology and clinical efficacy. Drugs. 1998 Feb;55(2):173-89. [9506240 ]
  4. Gan TJ: Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting: are they all the same? CNS Drugs. 2005;19(3):225-38. [15740177 ]
  5. Tramer MR, Reynolds DJ, Moore RA, McQuay HJ: Efficacy, dose-response, and safety of ondansetron in prevention of postoperative nausea and vomiting: a quantitative systematic review of randomized placebo-controlled trials. Anesthesiology. 1997 Dec;87(6):1277-89. [9416710 ]
  6. Graves T: Ondansetron: a new entity in emesis control. DICP. 1990 Nov;24(11 Suppl):S51-4. [2148659 ]
  7. Drugs.com [Link]
  8. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Voltage-gated potassium channel activity
Specific Function:
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel.
Gene Name:
HTR3A
Uniprot ID:
P46098
Molecular Weight:
55279.835 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0028 uMNot AvailableBindingDB 50000493
Inhibitory0.0034 uMNot AvailableBindingDB 50000493
Inhibitory0.016 uMNot AvailableBindingDB 50000493
IC500.00009 uMNot AvailableBindingDB 50000493
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Artaiz I, Zazpe A, Del Rio J: Characterization of serotonergic mechanisms involved in the behavioural inhibition induced by 5-hydroxytryptophan in a modified light-dark test in mice. Behav Pharmacol. 1998 Mar;9(2):103-12. [10065930 ]
  3. Fortuno A, Ballaz S, Del Rio J, Barber A: CCK-mediated response in the activation of 5-HT receptor types in the guinea-pig ileum. J Physiol Biochem. 1999 Jun;55(2):85-92. [10517265 ]
  4. Llacer JM, Gallardo V, Delgado R, Parraga J, Martin D, Ruiz MA: X-ray diffraction and electron microscopy in the polymorphism study of ondansetron hydrochloride. Drug Dev Ind Pharm. 2001 Oct;27(9):899-908. [11763467 ]
  5. Carvalho F, Macedo D, Bandeira I, Maldonado I, Salles L, Azevedo MF, Rocha MA Jr, Fregoneze JB, De Castro-e-Silva E: Central 5-HT3 receptor stimulation by m-CPBG increases blood glucose in rats. Horm Metab Res. 2002 Feb;34(2):55-61. [11972287 ]
  6. Arcioni R, della Rocca M, Romano S, Romano R, Pietropaoli P, Gasparetto A: Ondansetron inhibits the analgesic effects of tramadol: a possible 5-HT(3) spinal receptor involvement in acute pain in humans. Anesth Analg. 2002 Jun;94(6):1553-7, table of contents. [12032025 ]
  7. Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mork A, Stensbol TB: Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12. [21486038 ]
  8. Yang Z, Fairfax DJ, Maeng JH, Masih L, Usyatinsky A, Hassler C, Isaacson S, Fitzpatrick K, DeOrazio RJ, Chen J, Harding JP, Isherwood M, Dobritsa S, Christensen KL, Wierschke JD, Bliss BI, Peterson LH, Beer CM, Cioffi C, Lynch M, Rennells WM, Richards JJ, Rust T, Khmelnitsky YL, Cohen ML, Manning DD: Discovery of 2-substituted benzoxazole carboxamides as 5-HT3 receptor antagonists. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6538-41. doi: 10.1016/j.bmcl.2010.09.038. Epub 2010 Sep 16. [20889341 ]
  9. Rizzi JP, Nagel AA, Rosen T, McLean S, Seeger T: An initial three-component pharmacophore for specific serotonin-3 receptor ligands. J Med Chem. 1990 Oct;33(10):2721-5. [2145434 ]
  10. Rosen T, Nagel AA, Rizzi JP, Ives JL, Daffeh JB, Ganong AH, Guarino K, Heym J, McLean S, Nowakowski JT, et al.: Thiazole as a carbonyl bioisostere. A novel class of highly potent and selective 5-HT3 receptor antagonists. J Med Chem. 1990 Oct;33(10):2715-20. [2213824 ]
  11. Ramsook C, Sahagun-Carreon I, Kozinetz CA, Moro-Sutherland D: A randomized clinical trial comparing oral ondansetron with placebo in children with vomiting from acute gastroenteritis. Ann Emerg Med. 2002 Apr;39(4):397-403. [11919526 ]
General Function:
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function:
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular Weight:
126653.52 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.4 uMNot AvailableBindingDB 50000493
IC500.81283 uMNot AvailableBindingDB 50000493
IC500.813 uMNot AvailableBindingDB 50000493
References
  1. Yang Z, Fairfax DJ, Maeng JH, Masih L, Usyatinsky A, Hassler C, Isaacson S, Fitzpatrick K, DeOrazio RJ, Chen J, Harding JP, Isherwood M, Dobritsa S, Christensen KL, Wierschke JD, Bliss BI, Peterson LH, Beer CM, Cioffi C, Lynch M, Rennells WM, Richards JJ, Rust T, Khmelnitsky YL, Cohen ML, Manning DD: Discovery of 2-substituted benzoxazole carboxamides as 5-HT3 receptor antagonists. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6538-41. doi: 10.1016/j.bmcl.2010.09.038. Epub 2010 Sep 16. [20889341 ]
  2. Tobita M, Nishikawa T, Nagashima R: A discriminant model constructed by the support vector machine method for HERG potassium channel inhibitors. Bioorg Med Chem Lett. 2005 Jun 2;15(11):2886-90. [15911273 ]
  3. Jia L, Sun H: Support vector machines classification of hERG liabilities based on atom types. Bioorg Med Chem. 2008 Jun 1;16(11):6252-60. doi: 10.1016/j.bmc.2008.04.028. Epub 2008 Apr 16. [18448342 ]
  4. Keseru GM: Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods. Bioorg Med Chem Lett. 2003 Aug 18;13(16):2773-5. [12873512 ]
3. Serotonin Receptors (Protein Group)
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.
Included Proteins:
P08908 , P28222 , P28221 , P28566 , P30939 , P28223 , P41595 , P28335 , P46098 , O95264 , Q8WXA8 , Q70Z44 , A5X5Y0 , Q13639 , P50406 , P34969
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0076 uMNot AvailableBindingDB 50000493
Inhibitory0.012 uMNot AvailableBindingDB 50000493
Dissociation0.0000794 uMNot AvailableBindingDB 50000493
Dissociation0.000398 uMNot AvailableBindingDB 50000493
Dissociation0.05012 uMNot AvailableBindingDB 50000493
References
  1. Hibert MF, Hoffmann R, Miller RC, Carr AA: Conformation-activity relationship study of 5-HT3 receptor antagonists and a definition of a model for this receptor site. J Med Chem. 1990 Jun;33(6):1594-600. [2342053 ]
  2. Kishibayashi N, Miwa Y, Hayashi H, Ishii A, Ichikawa S, Nonaka H, Yokoyama T, Suzuki F: 5-HT3 receptor antagonists. 3. Quinoline derivatives which may be effective in the therapy of irritable bowel syndrome. J Med Chem. 1993 Oct 29;36(22):3286-92. [8230119 ]
  3. Macor JE, Gurley D, Lanthorn T, Loch J, Mack RA, Mullen G, Tran O, Wright N, Gordon JC: The 5-HT3 antagonist tropisetron (ICS 205-930) is a potent and selective alpha7 nicotinic receptor partial agonist. Bioorg Med Chem Lett. 2001 Feb 12;11(3):319-21. [11212100 ]
General Function:
Monovalent cation:proton antiporter activity
Specific Function:
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, ganciclovir and also the zwitterionic cephalosporin, cephalexin and cephradin. Seems to also play a role in the uptake of oxaliplatin (a new platinum anticancer agent). Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used herbicid. Responsible for the secretion of cationic drugs across the brush border membranes.
Gene Name:
SLC47A1
Uniprot ID:
Q96FL8
Molecular Weight:
61921.585 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.03 uMNot AvailableBindingDB 50000493
IC500.15 uMNot AvailableBindingDB 50000493
IC500.16 uMNot AvailableBindingDB 50000493
References
  1. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]
  2. Kido Y, Matsson P, Giacomini KM: Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. J Med Chem. 2011 Jul 14;54(13):4548-58. doi: 10.1021/jm2001629. Epub 2011 Jun 8. [21599003 ]
General Function:
Drug transmembrane transporter activity
Specific Function:
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, and ganciclovir. Responsible for the secretion of cationic drugs across the brush border membranes.
Gene Name:
SLC47A2
Uniprot ID:
Q86VL8
Molecular Weight:
65083.915 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.3 uMNot AvailableBindingDB 50000493
IC506.9 uMNot AvailableBindingDB 50000493
References
  1. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]
  2. Kido Y, Matsson P, Giacomini KM: Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. J Med Chem. 2011 Jul 14;54(13):4548-58. doi: 10.1021/jm2001629. Epub 2011 Jun 8. [21599003 ]
General Function:
Ligand-gated ion channel activity
Specific Function:
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodium ions.
Gene Name:
CHRNA4
Uniprot ID:
P43681
Molecular Weight:
69956.47 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory46 uMNot AvailableBindingDB 50000493
IC5066 uMNot AvailableBindingDB 50000493
References
  1. Papke RL, Porter Papke JK, Rose GM: Activity of alpha7-selective agonists at nicotinic and serotonin 5HT3 receptors expressed in Xenopus oocytes. Bioorg Med Chem Lett. 2004 Apr 19;14(8):1849-53. [15050614 ]
  2. Macor JE, Gurley D, Lanthorn T, Loch J, Mack RA, Mullen G, Tran O, Wright N, Gordon JC: The 5-HT3 antagonist tropisetron (ICS 205-930) is a potent and selective alpha7 nicotinic receptor partial agonist. Bioorg Med Chem Lett. 2001 Feb 12;11(3):319-21. [11212100 ]
General Function:
Secondary active organic cation transmembrane transporter activity
Specific Function:
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin-dependent kinase II and LCK tyrosine kinase.
Gene Name:
SLC22A1
Uniprot ID:
O15245
Molecular Weight:
61153.345 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>100 uMNot AvailableBindingDB 50000493
IC50>300 uMNot AvailableBindingDB 50000493
References
  1. Kido Y, Matsson P, Giacomini KM: Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. J Med Chem. 2011 Jul 14;54(13):4548-58. doi: 10.1021/jm2001629. Epub 2011 Jun 8. [21599003 ]
  2. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]
General Function:
Quaternary ammonium group transmembrane transporter activity
Specific Function:
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity.
Gene Name:
SLC22A2
Uniprot ID:
O15244
Molecular Weight:
62579.99 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.89 uMNot AvailableBindingDB 50000493
IC501.7 uMNot AvailableBindingDB 50000493
References
  1. Kido Y, Matsson P, Giacomini KM: Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. J Med Chem. 2011 Jul 14;54(13):4548-58. doi: 10.1021/jm2001629. Epub 2011 Jun 8. [21599003 ]
  2. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.
Gene Name:
HTR1A
Uniprot ID:
P08908
Molecular Weight:
46106.335 Da
References
  1. van Wijngaarden I, Tulp MT, Soudijn W: The concept of selectivity in 5-HT receptor research. Eur J Pharmacol. 1990 Jun 12;188(6):301-12. [2164935 ]
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances, such as lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior. Besides, plays a role in vasoconstriction of cerebral arteries.
Gene Name:
HTR1B
Uniprot ID:
P28222
Molecular Weight:
43567.535 Da
References
  1. van Wijngaarden I, Tulp MT, Soudijn W: The concept of selectivity in 5-HT receptor research. Eur J Pharmacol. 1990 Jun 12;188(6):301-12. [2164935 ]
General Function:
Serotonin receptor activity
Specific Function:
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase.
Gene Name:
HTR4
Uniprot ID:
Q13639
Molecular Weight:
43760.975 Da
References
  1. van Wijngaarden I, Tulp MT, Soudijn W: The concept of selectivity in 5-HT receptor research. Eur J Pharmacol. 1990 Jun 12;188(6):301-12. [2164935 ]
General Function:
Serotonin receptor activity
Specific Function:
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs (By similarity). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of TOR signaling (PubMed:23027611).
Gene Name:
HTR6
Uniprot ID:
P50406
Molecular Weight:
46953.625 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5011 uMNot AvailableBindingDB 50000493
References
  1. Yang Z, Fairfax DJ, Maeng JH, Masih L, Usyatinsky A, Hassler C, Isaacson S, Fitzpatrick K, DeOrazio RJ, Chen J, Harding JP, Isherwood M, Dobritsa S, Christensen KL, Wierschke JD, Bliss BI, Peterson LH, Beer CM, Cioffi C, Lynch M, Rennells WM, Richards JJ, Rust T, Khmelnitsky YL, Cohen ML, Manning DD: Discovery of 2-substituted benzoxazole carboxamides as 5-HT3 receptor antagonists. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6538-41. doi: 10.1016/j.bmcl.2010.09.038. Epub 2010 Sep 16. [20889341 ]
General Function:
Voltage-gated calcium channel activity
Specific Function:
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects. Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.
Gene Name:
OPRM1
Uniprot ID:
P35372
Molecular Weight:
44778.855 Da
References
  1. van Wijngaarden I, Tulp MT, Soudijn W: The concept of selectivity in 5-HT receptor research. Eur J Pharmacol. 1990 Jun 12;188(6):301-12. [2164935 ]
General Function:
Toxin transporter activity
Specific Function:
Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
Gene Name:
SLC22A3
Uniprot ID:
O75751
Molecular Weight:
61279.485 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5017.4 uMNot AvailableBindingDB 50000493
References
  1. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]