Posiphen
Phenyl carbamoyl analogues of physostigmine-esrine were developed to provide longer acting and better tolerated Alzheimer's disease treatment. Posiphen (enantiomer of phenserine: ANVS401 (+)-phenserine) is under investigation in clinical trial NCT02925650 (Early Alzheimer's Disease) Posiphen does not inhibit AChE or BChE, but its major and minor metabolites (+)-N1-norPosiphen and (+)-N1,N8-bisnorPosiphen, respectively, possessed modest AChE inhibitory activity.
General
Type : Derivative of physostigmine-eserine, Carbamate, Drug, Indole
Chemical_Nomenclature : [(3aS,8bR)-3,4,8b-trimethyl-2,3a-dihydro-1H-pyrrolo[2,3-b]indol-7-yl] N-phenylcarbamate
Canonical SMILES : CC12CCN(C1N(C3=C2C=C(C=C3)OC(=O)NC4=CC=CC=C4)C)C
InChI : InChI=1S\/C20H23N3O2\/c1-20-11-12-22(2)18(20)23(3)17-10-9-15(13-16(17)20)25-19(24)21-14-7-5-4-6-8-14\/h4-10,13,18H,11-12H2,1-3H3,(H,21,24)\/t18-,20+\/m0\/s1
InChIKey : PBHFNBQPZCRWQP-AZUAARDMSA-N
Other name(s) : posiphen, (+)-phenserine, (+)-Posiphen, Phenserine, (+)-, Buntanetap, R-Phenserine, DB15317, CHEMBL4297417, SCHEMBL23874278
MW : 337.4
Formula : C20H23N3O2
CAS_number : 116839-68-0
PubChem : 11249342
UniChem : PBHFNBQPZCRWQP-AZUAARDMSA-N
Target
Families : Posiphen ligand of proteins in family
ACHE
References (8)
| Title : In Silico and Ex Vivo Analyses of the Inhibitory Action of the Alzheimer Drug Posiphen and Primary Metabolites with Human Acetyl- and Butyrylcholinesterase Enzymes - Batool_2022_ACS.Pharmacol.Transl.Sci_5_70 |
| Author(s) : Batool S , Furqan T , Hasan Mahmood MS , Tweedie D , Kamal MA , Greig NH |
| Ref : ACS Pharmacol Transl Sci , 5 :70 , 2022 |
| PubMedID: 35178511 |
| Title : (-)-Phenserine Ameliorates Contusion Volume, Neuroinflammation, and Behavioral Impairments Induced by Traumatic Brain Injury in Mice - Hsueh_2019_Cell.Transplant_28_1183 |
| Author(s) : Hsueh SC , Lecca D , Greig NH , Wang JY , Selman W , Hoffer BJ , Miller JP , Chiang YH |
| Ref : Cell Transplantation , 28 :1183 , 2019 |
| PubMedID: 31177840 |
| Title : Alzheimer's Disease and Its Potential Alternative Therapeutics - Kisby_2019_J.Alzheimers.Dis.Parkinsonism_9_ |
| Author(s) : Kisby B , Jarrell JT , Agar ME , Cohen DS , Rosin ER , Cahill CM , Rogers JT , Huang X |
| Ref : J Alzheimers Dis Parkinsonism , 9 : , 2019 |
| PubMedID: 31588368 |
| Title : Synthesis of the Alzheimer Drug Posiphen into its Primary Metabolic Products (+)-N1-norPosiphen, (+)-N8-norPosiphen and (+)-N1, N8-bisnorPosiphen, their Inhibition of Amyloid Precursor Protein, alpha -Synuclein Synthesis, Interleukin-1beta Release, and Cholinergic Action - Yu_2013_Antiinflamm.Antiallergy.Agents.Med.Chem_12_117 |
| Author(s) : Yu QS , Reale M , Kamal MA , Holloway HW , Luo W , Sambamurti K , Ray B , Lahiri DK , Rogers JT , Greig NH |
| Ref : Antiinflamm Antiallergy Agents Med Chem , 12 :117 , 2013 |
| PubMedID: 23360256 |
| Title : The anticholinesterase phenserine and its enantiomer posiphen as 5'untranslated-region-directed translation blockers of the Parkinson's alpha synuclein expression - Mikkilineni_2012_Parkinsons.Dis_2012_142372 |
| Author(s) : Mikkilineni S , Cantuti-Castelvetri I , Cahill CM , Balliedier A , Greig NH , Rogers JT |
| Ref : Parkinsons Dis , 2012 :142372 , 2012 |
| PubMedID: 22693681 |
| Title : The experimental Alzheimer's disease drug posiphen [(+)-phenserine] lowers amyloid-beta peptide levels in cell culture and mice - Lahiri_2007_J.Pharmacol.Exp.Ther_320_386 |
| Author(s) : Lahiri DK , Chen D , Maloney B , Holloway HW , Yu QS , Utsuki T , Giordano T , Sambamurti K , Greig NH |
| Ref : Journal of Pharmacology & Experimental Therapeutics , 320 :386 , 2007 |
| PubMedID: 17003227 |
| Title : Phenserine - Klein_2007_Expert.Opin.Investig.Drugs_16_1087 |
| Author(s) : Klein J |
| Ref : Expert Opin Investig Drugs , 16 :1087 , 2007 |
| PubMedID: 17594192 |