T3DB: Tacrine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (16)XML

Targets (16)

Record Information

Version

2.0

Creation Date

2009-07-21 20:26:45 UTC

Update Date

2014-12-24 20:25:51 UTC

Accession Number

T3D2772

Identification

Common Name

Tacrine

Class

Small Molecule

Description

Tacrine is only found in individuals that have used or taken this drug. It is a centerally active cholinesterase inhibitor that has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders. The mechanism of tacrine is not fully known, but it is suggested that the drug is an anticholinesterase agent which reversibly binds with and inactivates cholinesterases. This inhibits the hydrolysis of acetylcholine released from functioning cholinergic neurons, thus leading to an accumulation of acetylcholine at cholinergic synapses. The result is a prolonged effect of acetylcholine.

Compound Type

Amine
Cholinesterase Inhibitor
Drug
Metabolite
Nootropic Agent
Organic Compound
Parasympathomimetic
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
1,2,3,4-tetrahydroacridin-9-amine
Cognex
Tacrin
Tacrinum
Talem
Tetrahydroaminacrine
Tetrahydroaminoacridine
Tetrahydroaminocrin
Tetrahydroaminocrine
THA

Chemical Formula

C₁₃H₁₄N₂

Average Molecular Mass

198.264 g/mol

Monoisotopic Mass

198.116 g/mol

CAS Registry Number

321-64-2

IUPAC Name

1,2,3,4-tetrahydroacridin-9-amine

Traditional Name

tacrine

SMILES

N=C1C2=C(CCCC2)NC2=CC=CC=C12

InChI Identifier

InChI=1S/C13H14N2/c14-13-9-5-1-3-7-11(9)15-12-8-4-2-6-10(12)13/h1,3,5,7H,2,4,6,8H2,(H2,14,15)

InChI Key

InChIKey=YLJREFDVOIBQDA-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as acridines. These are organic compounds containing the acridine moiety, a linear tricyclic heterocycle which consists of two benzene rings joined by a pyridine ring.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Quinolines and derivatives

Sub Class

Benzoquinolines

Direct Parent

Acridines

Alternative Parents

Substituents

Acridine
4-aminoquinoline
Aminoquinoline
Aminopyridine
Benzenoid
Pyridine
Heteroaromatic compound
Azacycle
Organic nitrogen compound
Organopnictogen compound
Hydrocarbon derivative
Primary amine
Organonitrogen compound
Amine
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

aromatic amine (CHEBI:45980 )
acridines (CHEBI:45980 )
a small molecule (CPD-10887 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

EC 3.1.1.7 (acetylcholinesterase) inhibitor

Chemical Roles

EC 3.1.1.7 (acetylcholinesterase) inhibitor

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	183.5°C
Boiling Point	Not Available
Solubility	217 mg/L
LogP	2.71

Predicted Properties

Property	Value	Source
Water Solubility	0.14 g/L	ALOGPS
logP	3.13	ALOGPS
logP	2.63	ChemAxon
logS	-3.2	ALOGPS
pKa (Strongest Basic)	8.95	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	38.91 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	61.74 m³·mol⁻¹	ChemAxon
Polarizability	22.79 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-00r2-0900000000-e2921d2cb64d7c502a4b	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-0002-0900000000-453e4e963f034e9de4cf	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-0002-0900000000-256a5702a96325bc74f2	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-0002-0900000000-af483bfb98e7e2b87b39	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-006t-0900000000-3c9902ca237f9c26a2fb	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-006x-0900000000-dec59115a19fdec78a9f	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-0002-0900000000-c04cbf634e493a774cd5	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 90V, Positive	splash10-006t-0900000000-2ea3694383dd21b13356	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 15V, Positive	splash10-0002-0900000000-2ffc3da62f3c0184f7c5	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Positive	splash10-0002-0900000000-676b079fd7de743702db	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Positive	splash10-0002-0900000000-67a5eac4e8faa4d5cd65	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 45V, Positive	splash10-0002-0900000000-b04e175289861dc518f1	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 90V, Positive	splash10-006t-0900000000-9ebb090b4661d7668df3	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 60V, Positive	splash10-0002-0900000000-f2347baf04672bb9e5bb	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 75V, Positive	splash10-0002-0900000000-9a37bfbb7353bd8bce87	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-001j-0900000000-2f420836beda4ff3e6b2	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-001i-0900000000-2275f7938116d06948a0	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-001i-2900000000-1f84e054a206191e525d	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0002-0900000000-e9e614ab5237139c5988	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0002-0900000000-0903202525aeeeca151c	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-00l2-0900000000-ba164ed659e5620dad0a	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0002-0900000000-d2d648aa4423d0c7a455	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0002-0900000000-d2d648aa4423d0c7a455	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-014m-0900000000-28208ede76de2a1de764	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0002-0900000000-d89ea9976ffd35a15c71	2021-09-25	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0002-0900000000-d89ea9976ffd35a15c71	2021-09-25	View Spectrum

Toxicity Profile

Route of Exposure

Oral. Tacrine is rapidly absorbed. Absolute bioavailability of tacrine is approximately 17%.

Mechanism of Toxicity

Tacrine is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.

Metabolism

Hepatic. Cytochrome P450 1A2 is the principal isozyme involved in tacrine metabolism. The major metabolite, 1-hydroxy-tacrine (velnacrine), has central cholinergic activity. Half Life: 2 to 4 hours

Toxicity Values

Not Available

Lethal Dose

The estimated median lethal dose of tacrine following a single oral dose in rats is 40 mg/kg, or approximately 12 times the maximum recommended human dose of 160 mg/day.

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For the palliative treatment of mild to moderate dementia of the Alzheimer's type.

Minimum Risk Level

Not Available

Health Effects

Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.

Symptoms

Overdosage with cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved.

Treatment

If the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

9389

BioCyc ID

CPD-10887

CTD ID

Not Available

Stitch ID

Tacrine

PDB ID

THA

ACToR ID

Not Available

Wikipedia Link

Tacrine

References

Synthesis Reference

S. Shirley Yang, Wayne Boisvert, Nouman A. Muhammad, Jay Weiss, “Controlled release tacrine drug delivery systems and methods for preparing same.” U.S. Patent US5576022, issued February, 1993.

MSDS

Link

General References

Qizilbash N, Whitehead A, Higgins J, Wilcock G, Schneider L, Farlow M: Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials. Dementia Trialists' Collaboration. JAMA. 1998 Nov 25;280(20):1777-82. [9842955 ]
Hansen RA, Gartlehner G, Kaufer DJ, Lohr KN, Carey T: [20480924 ]
Drugs.com [Link]
RxList: The Internet Drug Index (2009). [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Acetylcholinesterase

General Function:: Serine hydrolase activity
Specific Function:: Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name:: ACHE
Uniprot ID:: P22303
Molecular Weight:: 67795.525 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.0069 uM	Not Available	BindingDB 8961
Inhibitory	0.03212 uM	Not Available	BindingDB 8961
Inhibitory	0.036 uM	Not Available	BindingDB 8961
Inhibitory	0.04 uM	Not Available	BindingDB 8961
Inhibitory	0.137 uM	Not Available	BindingDB 8961
Inhibitory	0.151 uM	Not Available	BindingDB 8961
IC50	0.03 uM	Not Available	BindingDB 8961
IC50	0.0335 uM	Not Available	BindingDB 8961
IC50	0.034 uM	Not Available	BindingDB 8961
IC50	0.0451 uM	Not Available	BindingDB 8961
IC50	0.047 uM	Not Available	BindingDB 8961
IC50	0.052 uM	Not Available	BindingDB 8961
IC50	0.075 uM	Not Available	BindingDB 8961
IC50	0.07603 uM	Not Available	BindingDB 8961
IC50	0.077 uM	Not Available	BindingDB 8961
IC50	0.078 uM	Not Available	BindingDB 8961
IC50	0.09 uM	Not Available	BindingDB 8961
IC50	0.095 uM	Not Available	BindingDB 8961
IC50	0.1 uM	Not Available	BindingDB 8961
IC50	0.11 uM	Not Available	BindingDB 8961
IC50	0.122 uM	Not Available	BindingDB 8961
IC50	0.128 uM	Not Available	BindingDB 8961
IC50	0.143 uM	Not Available	BindingDB 8961
IC50	0.147 uM	Not Available	BindingDB 8961
IC50	0.15 uM	Not Available	BindingDB 8961
IC50	0.17 uM	Not Available	BindingDB 8961
IC50	0.18 uM	Not Available	BindingDB 8961
IC50	0.19 uM	Not Available	BindingDB 8961
IC50	0.2 uM	Not Available	BindingDB 8961
IC50	0.205 uM	Not Available	BindingDB 8961
IC50	0.25 uM	Not Available	BindingDB 8961
IC50	0.251 uM	Not Available	BindingDB 8961
IC50	0.254 uM	Not Available	BindingDB 8961
IC50	0.267 uM	Not Available	BindingDB 8961
IC50	0.26977 uM	Not Available	BindingDB 8961
IC50	0.27 uM	Not Available	BindingDB 8961
IC50	0.317 uM	Not Available	BindingDB 8961
IC50	0.35 uM	Not Available	BindingDB 8961
IC50	0.42 uM	Not Available	BindingDB 8961
IC50	0.424 uM	Not Available	BindingDB 8961
IC50	0.484 uM	Not Available	BindingDB 8961
IC50	0.5 uM	Not Available	BindingDB 8961
IC50	0.8 uM	Not Available	BindingDB 8961
IC50	0.926 uM	Not Available	BindingDB 8961
IC50	1.03 uM	Not Available	BindingDB 8961
IC50	3.16 uM	Not Available	BindingDB 8961

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Camps P, Gomez E, Munoz-Torrero D, Badia A, Clos MV, Curutchet C, Munoz-Muriedas J, Luque FJ: Binding of 13-amidohuprines to acetylcholinesterase: exploring the ligand-induced conformational change of the gly117-gly118 peptide bond in the oxyanion hole. J Med Chem. 2006 Nov 16;49(23):6833-40. [17154513 ]
Rampa A, Bisi A, Belluti F, Gobbi S, Valenti P, Andrisano V, Cavrini V, Cavalli A, Recanatini M: Acetylcholinesterase inhibitors for potential use in Alzheimer's disease: molecular modeling, synthesis and kinetic evaluation of 11H-indeno-[1,2-b]-quinolin-10-ylamine derivatives. Bioorg Med Chem. 2000 Mar;8(3):497-506. [10732965 ]
Recanatini M, Cavalli A, Belluti F, Piazzi L, Rampa A, Bisi A, Gobbi S, Valenti P, Andrisano V, Bartolini M, Cavrini V: SAR of 9-amino-1,2,3,4-tetrahydroacridine-based acetylcholinesterase inhibitors: synthesis, enzyme inhibitory activity, QSAR, and structure-based CoMFA of tacrine analogues. J Med Chem. 2000 May 18;43(10):2007-18. [10821713 ]
Rizzo S, Bisi A, Bartolini M, Mancini F, Belluti F, Gobbi S, Andrisano V, Rampa A: Multi-target strategy to address Alzheimer's disease: design, synthesis and biological evaluation of new tacrine-based dimers. Eur J Med Chem. 2011 Sep;46(9):4336-43. doi: 10.1016/j.ejmech.2011.07.004. Epub 2011 Jul 8. [21798635 ]
Nagel AA, Liston DR, Jung S, Mahar M, Vincent LA, Chapin D, Chen YL, Hubbard S, Ives JL, Jones SB, et al.: Design and synthesis of 1-heteroaryl-3-(1-benzyl-4-piperidinyl)propan-1-one derivatives as potent, selective acetylcholinesterase inhibitors. J Med Chem. 1995 Mar 31;38(7):1084-9. [7707311 ]
Cappelli A, Gallelli A, Manini M, Anzini M, Mennuni L, Makovec F, Menziani MC, Alcaro S, Ortuso F, Vomero S: Further studies on the interaction of the 5-hydroxytryptamine3 (5-HT3) receptor with arylpiperazine ligands. development of a new 5-HT3 receptor ligand showing potent acetylcholinesterase inhibitory properties. J Med Chem. 2005 May 19;48(10):3564-75. [15887964 ]
Tong W, Collantes ER, Chen Y, Welsh WJ: A comparative molecular field analysis study of N-benzylpiperidines as acetylcholinesterase inhibitors. J Med Chem. 1996 Jan 19;39(2):380-7. [8558505 ]
Villalobos A, Blake JF, Biggers CK, Butler TW, Chapin DS, Chen YL, Ives JL, Jones SB, Liston DR, Nagel AA, et al.: Novel benzisoxazole derivatives as potent and selective inhibitors of acetylcholinesterase. J Med Chem. 1994 Aug 19;37(17):2721-34. [8064800 ]
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Rodriguez-Franco MI, Fernandez-Bachiller MI, Perez C, Hernandez-Ledesma B, Bartolome B: Novel tacrine-melatonin hybrids as dual-acting drugs for Alzheimer disease, with improved acetylcholinesterase inhibitory and antioxidant properties. J Med Chem. 2006 Jan 26;49(2):459-62. [16420031 ]
Arce MP, Rodriguez-Franco MI, Gonzalez-Munoz GC, Perez C, Lopez B, Villarroya M, Lopez MG, Garcia AG, Conde S: Neuroprotective and cholinergic properties of multifunctional glutamic acid derivatives for the treatment of Alzheimer's disease. J Med Chem. 2009 Nov 26;52(22):7249-57. doi: 10.1021/jm900628z. [19856923 ]
Fernandez-Bachiller MI, Perez C, Gonzalez-Munoz GC, Conde S, Lopez MG, Villarroya M, Garcia AG, Rodriguez-Franco MI: Novel tacrine-8-hydroxyquinoline hybrids as multifunctional agents for the treatment of Alzheimer's disease, with neuroprotective, cholinergic, antioxidant, and copper-complexing properties. J Med Chem. 2010 Jul 8;53(13):4927-37. doi: 10.1021/jm100329q. [20545360 ]
Fernandez-Bachiller MI, Perez C, Monjas L, Rademann J, Rodriguez-Franco MI: New tacrine-4-oxo-4H-chromene hybrids as multifunctional agents for the treatment of Alzheimer's disease, with cholinergic, antioxidant, and beta-amyloid-reducing properties. J Med Chem. 2012 Feb 9;55(3):1303-17. doi: 10.1021/jm201460y. Epub 2012 Jan 27. [22243648 ]
Maalej E, Chabchoub F, Oset-Gasque MJ, Esquivias-Perez M, Gonzalez MP, Monjas L, Perez C, de los Rios C, Rodriguez-Franco MI, Iriepa I, Moraleda I, Chioua M, Romero A, Marco-Contelles J, Samadi A: Synthesis, biological assessment, and molecular modeling of racemic 7-aryl-9,10,11,12-tetrahydro-7H-benzo[7,8]chromeno[2,3-b]quinolin-8-amines as potential drugs for the treatment of Alzheimer's disease. Eur J Med Chem. 2012 Aug;54:750-63. doi: 10.1016/j.ejmech.2012.06.038. Epub 2012 Jun 28. [22795665 ]
Samadi A, de los Rios C, Bolea I, Chioua M, Iriepa I, Moraleda I, Bartolini M, Andrisano V, Galvez E, Valderas C, Unzeta M, Marco-Contelles J: Multipotent MAO and cholinesterase inhibitors for the treatment of Alzheimer's disease: synthesis, pharmacological analysis and molecular modeling of heterocyclic substituted alkyl and cycloalkyl propargyl amine. Eur J Med Chem. 2012 Jun;52:251-62. doi: 10.1016/j.ejmech.2012.03.022. Epub 2012 Mar 30. [22503231 ]
Bolognesi ML, Andrisano V, Bartolini M, Banzi R, Melchiorre C: Propidium-based polyamine ligands as potent inhibitors of acetylcholinesterase and acetylcholinesterase-induced amyloid-beta aggregation. J Med Chem. 2005 Jan 13;48(1):24-7. [15633997 ]
Rosini M, Andrisano V, Bartolini M, Bolognesi ML, Hrelia P, Minarini A, Tarozzi A, Melchiorre C: Rational approach to discover multipotent anti-Alzheimer drugs. J Med Chem. 2005 Jan 27;48(2):360-3. [15658850 ]
Bolognesi ML, Banzi R, Bartolini M, Cavalli A, Tarozzi A, Andrisano V, Minarini A, Rosini M, Tumiatti V, Bergamini C, Fato R, Lenaz G, Hrelia P, Cattaneo A, Recanatini M, Melchiorre C: Novel class of quinone-bearing polyamines as multi-target-directed ligands to combat Alzheimer's disease. J Med Chem. 2007 Oct 4;50(20):4882-97. Epub 2007 Sep 13. [17850125 ]
Bolognesi ML, Cavalli A, Valgimigli L, Bartolini M, Rosini M, Andrisano V, Recanatini M, Melchiorre C: Multi-target-directed drug design strategy: from a dual binding site acetylcholinesterase inhibitor to a trifunctional compound against Alzheimer's disease. J Med Chem. 2007 Dec 27;50(26):6446-9. Epub 2007 Nov 30. [18047264 ]
Cavalli A, Bolognesi ML, Minarini A, Rosini M, Tumiatti V, Recanatini M, Melchiorre C: Multi-target-directed ligands to combat neurodegenerative diseases. J Med Chem. 2008 Feb 14;51(3):347-72. doi: 10.1021/jm7009364. Epub 2008 Jan 9. [18181565 ]
Rosini M, Simoni E, Bartolini M, Cavalli A, Ceccarini L, Pascu N, McClymont DW, Tarozzi A, Bolognesi ML, Minarini A, Tumiatti V, Andrisano V, Mellor IR, Melchiorre C: Inhibition of acetylcholinesterase, beta-amyloid aggregation, and NMDA receptors in Alzheimer's disease: a promising direction for the multi-target-directed ligands gold rush. J Med Chem. 2008 Aug 14;51(15):4381-4. doi: 10.1021/jm800577j. Epub 2008 Jul 8. [18605718 ]
Rouleau J, Iorga BI, Guillou C: New potent human acetylcholinesterase inhibitors in the tetracyclic triterpene series with inhibitory potency on amyloid beta aggregation. Eur J Med Chem. 2011 Jun;46(6):2193-205. doi: 10.1016/j.ejmech.2011.02.073. Epub 2011 Mar 23. [21435752 ]
Korabecny J, Musilek K, Holas O, Binder J, Zemek F, Marek J, Pohanka M, Opletalova V, Dohnal V, Kuca K: Synthesis and in vitro evaluation of N-alkyl-7-methoxytacrine hydrochlorides as potential cholinesterase inhibitors in Alzheimer disease. Bioorg Med Chem Lett. 2010 Oct 15;20(20):6093-5. doi: 10.1016/j.bmcl.2010.08.044. Epub 2010 Aug 16. [20817518 ]
Korabecny J, Musilek K, Zemek F, Horova A, Holas O, Nepovimova E, Opletalova V, Hroudova J, Fisar Z, Jung YS, Kuca K: Synthesis and in vitro evaluation of 7-methoxy-N-(pent-4-enyl)-1,2,3,4-tetrahydroacridin-9-amine-new tacrine derivate with cholinergic properties. Bioorg Med Chem Lett. 2011 Nov 1;21(21):6563-6. doi: 10.1016/j.bmcl.2011.08.042. Epub 2011 Aug 22. [21920739 ]
Chaudhaery SS, Roy KK, Shakya N, Saxena G, Sammi SR, Nazir A, Nath C, Saxena AK: Novel carbamates as orally active acetylcholinesterase inhibitors found to improve scopolamine-induced cognition impairment: pharmacophore-based virtual screening, synthesis, and pharmacology. J Med Chem. 2010 Sep 9;53(17):6490-505. doi: 10.1021/jm100573q. [20684567 ]
Elsinghorst PW, Cieslik JS, Mohr K, Trankle C, Gutschow M: First gallamine-tacrine hybrid: design and characterization at cholinesterases and the M2 muscarinic receptor. J Med Chem. 2007 Nov 15;50(23):5685-95. Epub 2007 Oct 18. [17944454 ]
Sauvaitre T, Barlier M, Herlem D, Gresh N, Chiaroni A, Guenard D, Guillou C: New potent acetylcholinesterase inhibitors in the tetracyclic triterpene series. J Med Chem. 2007 Nov 1;50(22):5311-23. Epub 2007 Sep 29. [17902635 ]
Szymanski P, Karpinski A, Mikiciuk-Olasik E: Synthesis, biological activity and HPLC validation of 1,2,3,4-tetrahydroacridine derivatives as acetylcholinesterase inhibitors. Eur J Med Chem. 2011 Aug;46(8):3250-7. doi: 10.1016/j.ejmech.2011.04.038. Epub 2011 Apr 22. [21570751 ]
Bencharit S, Morton CL, Hyatt JL, Kuhn P, Danks MK, Potter PM, Redinbo MR: Crystal structure of human carboxylesterase 1 complexed with the Alzheimer's drug tacrine: from binding promiscuity to selective inhibition. Chem Biol. 2003 Apr;10(4):341-9. [12725862 ]
Peng DY, Sun Q, Zhu XL, Lin HY, Chen Q, Yu NX, Yang WC, Yang GF: Design, synthesis, and bioevaluation of benzamides: novel acetylcholinesterase inhibitors with multi-functions on butylcholinesterase, Abeta aggregation, and beta-secretase. Bioorg Med Chem. 2012 Nov 15;20(22):6739-50. doi: 10.1016/j.bmc.2012.09.016. Epub 2012 Sep 17. [23041347 ]
Butini S, Campiani G, Borriello M, Gemma S, Panico A, Persico M, Catalanotti B, Ros S, Brindisi M, Agnusdei M, Fiorini I, Nacci V, Novellino E, Belinskaya T, Saxena A, Fattorusso C: Exploiting protein fluctuations at the active-site gorge of human cholinesterases: further optimization of the design strategy to develop extremely potent inhibitors. J Med Chem. 2008 Jun 12;51(11):3154-70. doi: 10.1021/jm701253t. Epub 2008 May 15. [18479118 ]
Butini S, Guarino E, Campiani G, Brindisi M, Coccone SS, Fiorini I, Novellino E, Belinskaya T, Saxena A, Gemma S: Tacrine based human cholinesterase inhibitors: synthesis of peptidic-tethered derivatives and their effect on potency and selectivity. Bioorg Med Chem Lett. 2008 Oct 1;18(19):5213-6. doi: 10.1016/j.bmcl.2008.08.076. Epub 2008 Aug 26. [18786825 ]
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Campiani G, Fattorusso C, Butini S, Gaeta A, Agnusdei M, Gemma S, Persico M, Catalanotti B, Savini L, Nacci V, Novellino E, Holloway HW, Greig NH, Belinskaya T, Fedorko JM, Saxena A: Development of molecular probes for the identification of extra interaction sites in the mid-gorge and peripheral sites of butyrylcholinesterase (BuChE). Rational design of novel, selective, and highly potent BuChE inhibitors. J Med Chem. 2005 Mar 24;48(6):1919-29. [15771436 ]
Gemma S, Gabellieri E, Huleatt P, Fattorusso C, Borriello M, Catalanotti B, Butini S, De Angelis M, Novellino E, Nacci V, Belinskaya T, Saxena A, Campiani G: Discovery of huperzine A-tacrine hybrids as potent inhibitors of human cholinesterases targeting their midgorge recognition sites. J Med Chem. 2006 Jun 1;49(11):3421-5. [16722663 ]
Tumiatti V, Rosini M, Bartolini M, Cavalli A, Marucci G, Andrisano V, Angeli P, Banzi R, Minarini A, Recanatini M, Melchiorre C: Structure-activity relationships of acetylcholinesterase noncovalent inhibitors based on a polyamine backbone. 2. Role of the substituents on the phenyl ring and nitrogen atoms of caproctamine. J Med Chem. 2003 Mar 13;46(6):954-66. [12620072 ]

Target Details

2. Cholinesterase

General Function:: Identical protein binding
Specific Function:: Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name:: BCHE
Uniprot ID:: P06276
Molecular Weight:: 68417.575 Da

References

Wang H, Tang XC: Anticholinesterase effects of huperzine A, E2020, and tacrine in rats. Zhongguo Yao Li Xue Bao. 1998 Jan;19(1):27-30. [10375753 ]
Krustev AD, Argirova MD, Getova DP, Turiiski VI, Prissadova NA: Calcium-independent tacrine-induced relaxation of rat gastric corpus smooth muscles. Can J Physiol Pharmacol. 2006 Nov;84(11):1133-8. [17218977 ]
Marco JL, Carreiras MC: Recent developments in the synthesis of acetylcholinesterase inhibitors. Mini Rev Med Chem. 2003 Sep;3(6):518-24. [12871155 ]
Ahmed M, Rocha JB, Correa M, Mazzanti CM, Zanin RF, Morsch AL, Morsch VM, Schetinger MR: Inhibition of two different cholinesterases by tacrine. Chem Biol Interact. 2006 Aug 25;162(2):165-71. Epub 2006 Jun 17. [16860785 ]

Target Details

3. Acetylcholine receptor subunit epsilon

General Function:: Cation transmembrane transporter 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.
Gene Name:: CHRNE
Uniprot ID:: Q04844
Molecular Weight:: 54696.54 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	0.044 uM	Not Available	BindingDB 8961

References

Kapkova P, Heller E, Unger M, Folkers G, Holzgrabe U: Random chemistry as a new tool for the generation of small compound libraries: development of a new acetylcholinesterase inhibitor. J Med Chem. 2005 Nov 17;48(23):7496-9. [16279811 ]

Target Details

4. Cannabinoid receptor 1

General Function:: Drug binding
Specific Function:: Involved in cannabinoid-induced CNS effects. Acts by inhibiting adenylate cyclase. Could be a receptor for anandamide. Inhibits L-type Ca(2+) channel current. Isoform 2 and isoform 3 have altered ligand binding.
Gene Name:: CNR1
Uniprot ID:: P21554
Molecular Weight:: 52857.365 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	>1 uM	Not Available	BindingDB 8961

References

Lange JH, Coolen HK, van der Neut MA, Borst AJ, Stork B, Verveer PC, Kruse CG: Design, synthesis, biological properties, and molecular modeling investigations of novel tacrine derivatives with a combination of acetylcholinesterase inhibition and cannabinoid CB1 receptor antagonism. J Med Chem. 2010 Feb 11;53(3):1338-46. doi: 10.1021/jm901614b. [20047331 ]

Target Details

5. Cannabinoid receptor 2

General Function:: Cannabinoid receptor activity
Specific Function:: Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis.
Gene Name:: CNR2
Uniprot ID:: P34972
Molecular Weight:: 39680.275 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	>1 uM	Not Available	BindingDB 8961

References

Lange JH, Coolen HK, van der Neut MA, Borst AJ, Stork B, Verveer PC, Kruse CG: Design, synthesis, biological properties, and molecular modeling investigations of novel tacrine derivatives with a combination of acetylcholinesterase inhibition and cannabinoid CB1 receptor antagonism. J Med Chem. 2010 Feb 11;53(3):1338-46. doi: 10.1021/jm901614b. [20047331 ]

Target Details

6. Cocaine esterase

General Function:: Methylumbelliferyl-acetate deacetylase activity
Specific Function:: Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Shows high catalytic efficiency for hydrolysis of cocaine, 4-methylumbelliferyl acetate, heroin and 6-monoacetylmorphine.
Gene Name:: CES2
Uniprot ID:: O00748
Molecular Weight:: 61806.41 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	>100 uM	Not Available	BindingDB 8961

References

Bencharit S, Morton CL, Hyatt JL, Kuhn P, Danks MK, Potter PM, Redinbo MR: Crystal structure of human carboxylesterase 1 complexed with the Alzheimer's drug tacrine: from binding promiscuity to selective inhibition. Chem Biol. 2003 Apr;10(4):341-9. [12725862 ]

Target Details

7. Cytochrome P450 1A2

General Function:: Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:: CYP1A2
Uniprot ID:: P05177
Molecular Weight:: 58293.76 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	1.94 uM	Not Available	BindingDB 8961

References

Fontana E, Dansette PM, Poli SM: Cytochrome p450 enzymes mechanism based inhibitors: common sub-structures and reactivity. Curr Drug Metab. 2005 Oct;6(5):413-54. [16248836 ]

Target Details

8. Glutamate receptor ionotropic, NMDA 2A

General Function:: Zinc ion binding
Specific Function:: NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Activation requires binding of agonist to both types of subunits.
Gene Name:: GRIN2A
Uniprot ID:: Q12879
Molecular Weight:: 165281.215 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	4.9 uM	Not Available	BindingDB 8961

References

Rook Y, Schmidtke KU, Gaube F, Schepmann D, Wunsch B, Heilmann J, Lehmann J, Winckler T: Bivalent beta-carbolines as potential multitarget anti-Alzheimer agents. J Med Chem. 2010 May 13;53(9):3611-7. doi: 10.1021/jm1000024. [20361801 ]

Target Details

9. Glutamate receptor ionotropic, NMDA 2B

General Function:: Zinc ion binding
Specific Function:: NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death (By similarity).
Gene Name:: GRIN2B
Uniprot ID:: Q13224
Molecular Weight:: 166365.885 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	44 uM	Not Available	BindingDB 8961

References

Rook Y, Schmidtke KU, Gaube F, Schepmann D, Wunsch B, Heilmann J, Lehmann J, Winckler T: Bivalent beta-carbolines as potential multitarget anti-Alzheimer agents. J Med Chem. 2010 May 13;53(9):3611-7. doi: 10.1021/jm1000024. [20361801 ]

Target Details

10. Liver carboxylesterase 1

General Function:: Triglyceride lipase activity
Specific Function:: Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester. Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine. Catalyzes the transesterification of cocaine to form cocaethylene. Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate.
Gene Name:: CES1
Uniprot ID:: P23141
Molecular Weight:: 62520.62 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	>100 uM	Not Available	BindingDB 8961

References

Bencharit S, Morton CL, Hyatt JL, Kuhn P, Danks MK, Potter PM, Redinbo MR: Crystal structure of human carboxylesterase 1 complexed with the Alzheimer's drug tacrine: from binding promiscuity to selective inhibition. Chem Biol. 2003 Apr;10(4):341-9. [12725862 ]

Target Details

11. Metallothionein-2

General Function:: Zinc ion binding
Specific Function:: Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.
Gene Name:: MT2A
Uniprot ID:: P02795
Molecular Weight:: 6042.05 Da

References

Bencharit S, Morton CL, Hyatt JL, Kuhn P, Danks MK, Potter PM, Redinbo MR: Crystal structure of human carboxylesterase 1 complexed with the Alzheimer's drug tacrine: from binding promiscuity to selective inhibition. Chem Biol. 2003 Apr;10(4):341-9. [12725862 ]

Target Details

12. Multidrug and toxin extrusion protein 1

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

Type	Value	Assay Type	Assay Source
IC50	1.1 uM	Not Available	BindingDB 8961

References

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 ]

Target Details

13. Multidrug and toxin extrusion protein 2

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

Type	Value	Assay Type	Assay Source
IC50	>100 uM	Not Available	BindingDB 8961

References

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 ]

Target Details

14. Muscarinic acetylcholine receptor M2

General Function:: G-protein coupled acetylcholine receptor activity
Specific Function:: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
Gene Name:: CHRM2
Uniprot ID:: P08172
Molecular Weight:: 51714.605 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	5.8 uM	Not Available	BindingDB 8961

References

Valli MJ, Tang Y, Kosh JW, Chapman JM Jr, Sowell JW Sr: Synthesis and cholinergic properties of N-aryl-2-[[[5-[(dimethylamino)methyl]-2-furanyl]methyl]thio]ethylamino analogs of ranitidine. J Med Chem. 1992 Aug 21;35(17):3141-7. [1507203 ]

Target Details

15. Solute carrier family 22 member 1

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

Type	Value	Assay Type	Assay Source
IC50	83 uM	Not Available	BindingDB 8961

References

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 ]

Target Details

16. Solute carrier family 22 member 2

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

Type	Value	Assay Type	Assay Source
IC50	0.68 uM	Not Available	BindingDB 8961

References

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 ]

Tacrine (T3D2772)

Structure for T3D2772: Tacrine

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