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Inhibitor Report for: Tacrine

Tacrine is a cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine 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. Tacrine therapy is associated with a very high rate of serum aminotransferase elevations during therapy and has been linked to several instances of clinically apparent, acute liver injury. C13H14N2 * HCl MW 234.71 CAS 1684-40-8 Treatment of Alzheimer Disease, trademark is cognex. Reversible inhibitor of both AChE and BChE Tacrine is an oral acetylcholinesterase inhibitor previously used for therapy of Alzheimer disease. Tacrine therapy is associated with a very high rate of serum aminotransferase elevations during therapy and has been linked to several instances of clinically apparent, acute liver injury. release of endogenous 5-hydroxytryptamine (5-HT) not through a cholinergic, reserpine- or amphetamine-like mechanism or through inhibition of reuptake. The release may occur via blockade of 4-AP-insensitive K+ channels


General
Type Derivative of Tacrine, Acridine
Chemical_Nomenclature 1,2,3,4-tetrahydroacridin-9-amine
Canonical SMILES C1CCC2=NC3=CC=CC=C3C(=C2C1)N
InChI 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)
InChIKey YLJREFDVOIBQDA-UHFFFAOYSA-N
Other name(s) 1,2,3,4,-tetrahydro-9 aminoacridine ; Tetrahydroaminacrine ; Tetrahydroaminoacridine ; Cognex ; tetrahydroamino-acridine ; THA
________________________________________________________________________________________________
MW|198.27
Formula|C13H14N2
CAS_number|321-64-2
PubChem|1935
UniChem|YLJREFDVOIBQDA-UHFFFAOYSA-N
IUPHAR|6687
Wikipedia|

Target
Families | Tacrine ligand of proteins in family: ACHE
Stucture | 4 structures (e.g. : 1ACJ, 7XN1, 4BDS... more)
Protein | torca-ACHE, human-BCHE, human-CES1, human-ACHE

References:
Search PubMed for references concerning: Tacrine

68 more
    Title: Crystal structure of human acetylcholinesterase in complex with tacrine: Implications for drug discovery
    Dileep KV, Ihara K, Mishima-Tsumagari C, Kukimoto-Niino M, Yonemochi M, Hanada K, Shirouzu M, Zhang KYJ
    Ref: Int J Biol Macromol, 210:172, 2022 : PubMed

            

    Title: Kinetic analysis of the toxicological effect of tacrine (Cognex) on human retinal acetylcholinesterase activity
    Alhomida AS, Al-Rajhi AA, Kamal MA, Al-Jafari AA
    Ref: Toxicology, 147:33, 2000 : PubMed

            

    Title: The effect of cytochromes P4501A induction and inhibition on the disposition of the cognition activator tacrine in rat hepatic preparations
    Bezek S, Kukan M, Pool WF, Woolf TF
    Ref: Xenobiotica, 26:935, 1996 : PubMed

            


human-ACHE
MutationKiKsiIc50SubstrateConditionPaper
> Mutations for human-ACHE (22)

human-BCHE
MutationKiKsiIc50SubstrateConditionPaper
> Mutations for human-BCHE (24)

mouse-ACHE
MutationKiKsiIc50SubstrateConditionPaper
WT 40 & 10 nM 130 & 50 nM - Acetylthiocholine 100mM NaP pH7.0 T22C Radic_1993_Biochemistry_32_12074
Y337A 1.5 & 0.5 nM 5 & 1 nM - Acetylthiocholine 100mM NaP pH7.0 T22C Radic_1993_Biochemistry_32_12074
Y337F 150 & 30 nM 680 & 180 nM - Acetylthiocholine 100mM NaP pH7.0 T22C Radic_1993_Biochemistry_32_12074

mouse-BCHE
MutationKiKsiIc50SubstrateConditionPaper
WT 17 & 4 nM 47 & 22 nM - Acetylthiocholine 100mM NaP pH7.0 T22C Radic_1993_Biochemistry_32_12074

WT Kinetics
Kinetic parametersKiKsiIc50SubstrateConditionsPapers
human-ACHE0.21 uM-- Acetylthiocholine 50mM NaPhosphate pH7.4 Loewenstein-Lichtenstein_1996_Mol.Pharmacol_50_1423
human-ACHE12 nM-- Acetylthiocholine T25C IS 50 mM phosphate Kaplan_2001_Biochemistry_40_7433
human-ACHE85 & 12 nM 90 & 20 nM - Acetylthiocholine 50mM Na phosphate pH8 T22C Ariel_1998_Biochem.J_335_95
human-BCHE12 nM-- Acetylthiocholine T25C IS 50 mM phosphate Kaplan_2001_Biochemistry_40_7433
human-BCHE0.06 & 0.03 uM-- Butyrylthiocholine 50mM NaPhosphate pH7.4 Loewenstein-Lichtenstein_1996_Mol.Pharmacol_50_1423
mouse-ACHE40 & 10 nM130 & 50 nM- Acetylthiocholine 100mM NaP pH7.0 T22C Radic_1993_Biochemistry_32_12074
mouse-BCHE17 & 4 nM47 & 22 nM- Acetylthiocholine 100mM NaP pH7.0 T22C Radic_1993_Biochemistry_32_12074