Phenserine
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Phenserine
- DrugBank Accession Number
- DB04892
- Background
Phenserine is under development by Axonyx, a US biopharmaceutical company that focuses on treatments for dementia. Phenserine is a next generation acetylcholinesterase (AChE) inhibitor indicated for the treatment of AD. Unlike currently marketed AChE inhibitors, it has a dual mechanism of action that also includes anti-amyloid activity, which may confer disease-modifying effects in patients with AD. If this is substantiated in an ongoing clinical trial then phenserine may open the door to an entirely new type of treatment for AD. Axonyx announced on 20 September 2005 that phenserine was ineffective in two curtailed phase 3 trials.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 337.4155
Monoisotopic: 337.179026995 - Chemical Formula
- C20H23N3O2
- Synonyms
- (-)-eseroline phenylcarbamate
- (-)-phenserine
Pharmacology
- Indication
For the treatment of Alzheimer's disease (AD).
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- Pharmacodynamics
Phenserine, a phenylcarbamate of physostigmine, is a reversible acetyl-selective cholinesterase inhibitor. In studies of rats with lesions of the forebrain cholinergic system, injections of phenserine was found to significantly decrease the levels of secreted beta-APP in the CSF of the rats. A study on cultured human brain cells found that phenserine reduces Abeta levels by regulating beta-APP translation.
- Mechanism of action
Phenserine is a highly selective, reversible acetylcholinesterase inhibitor, a mechanism of action known to improve memory and cognition in Alzheimer’s subjects. Phenserine may prove to concentrate in the brain rapidly which would reduce the incidence of drug toxicity and side effects.
Target Actions Organism AAcetylcholinesterase inhibitorHumans ACholinesterase inhibitorHumans UAmyloid-beta precursor protein Not Available Humans - Absorption
Rapidly absorbed and cleared from the body.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
8 to 10 hours
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
The toxicity of phenserine, a derivate of physostigmine, is dramatically less. Doses of 20 mg/kg (rats, intravenous) of phenserine have not been associated with toxicity or deaths.
- 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 softwareAcebutolol Phenserine may increase the bradycardic activities of Acebutolol. Acetylcholine The risk or severity of adverse effects can be increased when Phenserine is combined with Acetylcholine. Aclidinium Phenserine may increase the neuromuscular blocking activities of Aclidinium. Amantadine The therapeutic efficacy of Amantadine can be decreased when used in combination with Phenserine. Amifampridine The risk or severity of adverse effects can be increased when Phenserine is combined with Amifampridine. - Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyrroloindoles. These are compounds containing a pyrroloindole moiety, which is a tricyclic heterocycle which consists of a pyrrole ring fused to an indole. Pyrrole is 5-membered ring consisting of four carbon atoms and one nitrogen atom. Indole is a bicyclic compound consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing pyrrole ring.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Indoles and derivatives
- Sub Class
- Pyrroloindoles
- Direct Parent
- Pyrroloindoles
- Alternative Parents
- Phenylcarbamic acid esters / Indoles / Dialkylarylamines / N-alkylpyrrolidines / Pyrroles / Carbamate esters / Organic carbonic acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organic oxides show 2 more
- Substituents
- Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbamic acid ester / Carbonic acid derivative / Carbonyl group / Dialkylarylamine / Hydrocarbon derivative / Indole / Monocyclic benzene moiety show 11 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- SUE285UG3S
- CAS number
- 101246-66-6
- InChI Key
- PBHFNBQPZCRWQP-QUCCMNQESA-N
- 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+/m1/s1
- IUPAC Name
- (3aS,8aR)-1,3a,8-trimethyl-1H,2H,3H,3aH,8H,8aH-pyrrolo[2,3-b]indol-5-yl N-phenylcarbamate
- SMILES
- [H][C@]12N(C)CC[C@@]1(C)C1=C(C=CC(OC(=O)NC3=CC=CC=C3)=C1)N2C
References
- General References
- Greig NH, Ruckle J, Comer P, Brownell L, Holloway HW, Flanagan DR Jr, Canfield CJ, Burford RG: Anticholinesterase and pharmacokinetic profile of phenserine in healthy elderly human subjects. Curr Alzheimer Res. 2005 Oct;2(4):483-92. [Article]
- Klein J: Phenserine. Expert Opin Investig Drugs. 2007 Jul;16(7):1087-97. [Article]
- Thatte U: Phenserine (Axonyx/NIH). IDrugs. 2000 Oct;3(10):1222-8. [Article]
- External Links
- PubChem Compound
- 192706
- PubChem Substance
- 175426894
- ChemSpider
- 167225
- BindingDB
- 10958
- ChEMBL
- CHEMBL74926
- ZINC
- ZINC000052968892
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 data
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 150 °C Not Available - Predicted Properties
Property Value Source Water Solubility 0.0509 mg/mL ALOGPS logP 3.38 ALOGPS logP 4.25 Chemaxon logS -3.8 ALOGPS pKa (Strongest Acidic) 12.86 Chemaxon pKa (Strongest Basic) 6.58 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 44.81 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 99.96 m3·mol-1 Chemaxon Polarizability 37.09 Å3 Chemaxon Number of Rings 4 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
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9959 Caco-2 permeable + 0.5664 P-glycoprotein substrate Substrate 0.6917 P-glycoprotein inhibitor I Inhibitor 0.6794 P-glycoprotein inhibitor II Inhibitor 0.6073 Renal organic cation transporter Non-inhibitor 0.6463 CYP450 2C9 substrate Non-substrate 0.7167 CYP450 2D6 substrate Non-substrate 0.6433 CYP450 3A4 substrate Substrate 0.7843 CYP450 1A2 substrate Non-inhibitor 0.8426 CYP450 2C9 inhibitor Non-inhibitor 0.8863 CYP450 2D6 inhibitor Inhibitor 0.8163 CYP450 2C19 inhibitor Non-inhibitor 0.8352 CYP450 3A4 inhibitor Non-inhibitor 0.5605 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6125 Ames test Non AMES toxic 0.8444 Carcinogenicity Non-carcinogens 0.9126 Biodegradation Not ready biodegradable 0.9256 Rat acute toxicity 4.3485 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8968 hERG inhibition (predictor II) Non-inhibitor 0.6199
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-0039000000-028baf5ce2c6d4fe262d Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-1249000000-403b07c9acc3f19de818 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-0039000000-a660f08d65df024bc22e Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0v4j-9743000000-1f1be00517b978712482 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-1091000000-949780f34ffce98cf448 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-02al-4981000000-aa13e4abd99d0e15b919 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]- 181.79996 predictedDeepCCS 1.0 (2019) [M+H]+ 184.15794 predictedDeepCCS 1.0 (2019) [M+Na]+ 190.60362 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis
- Specific Function
- acetylcholine binding
- Gene Name
- ACHE
- Uniprot ID
- P22303
- Uniprot Name
- Acetylcholinesterase
- Molecular Weight
- 67795.525 Da
References
- Greig NH, Ruckle J, Comer P, Brownell L, Holloway HW, Flanagan DR Jr, Canfield CJ, Burford RG: Anticholinesterase and pharmacokinetic profile of phenserine in healthy elderly human subjects. Curr Alzheimer Res. 2005 Oct;2(4):483-92. [Article]
- Klein J: Phenserine. Expert Opin Investig Drugs. 2007 Jul;16(7):1087-97. [Article]
- 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
- Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters
- Specific Function
- acetylcholinesterase activity
- Gene Name
- BCHE
- Uniprot ID
- P06276
- Uniprot Name
- Cholinesterase
- Molecular Weight
- 68417.575 Da
References
- Janas AM, Cunningham SC, Duffy KB, Devan BD, Greig NH, Holloway HW, Yu QS, Markowska AL, Ingram DK, Spangler EL: The cholinesterase inhibitor, phenserine, improves Morris water maze performance of scopolamine-treated rats. Life Sci. 2005 Jan 21;76(10):1073-81. [Article]
- 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
- Unknown
- General Function
- Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis (PubMed:25122912). Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(o) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1 (By similarity). By acting as a kinesin I membrane receptor, plays a role in axonal anterograde transport of cargo towards synapses in axons (PubMed:17062754, PubMed:23011729). Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1
- Specific Function
- DNA binding
- Gene Name
- APP
- Uniprot ID
- P05067
- Uniprot Name
- Amyloid-beta precursor protein
- Molecular Weight
- 86942.715 Da
References
- Venti A, Giordano T, Eder P, Bush AI, Lahiri DK, Greig NH, Rogers JT: The integrated role of desferrioxamine and phenserine targeted to an iron-responsive element in the APP-mRNA 5'-untranslated region. Ann N Y Acad Sci. 2004 Dec;1035:34-48. [Article]
Drug created at October 21, 2007 17:34 / Updated at August 26, 2024 19:23