Identification

Generic Name
Pozanicline
DrugBank Accession Number
DB05458
Background

ABT-089 is a neuronal nicotinic acetylcholine receptor agonist that may have therapeutic utility for the treatment of several neurological disorders including Alzheimer, Attention Deficit Hyperactivity Disorder and Schizophrenia/Schizoaffective disorders. In radioligand binding studies, ABT-089 has shown selectivity toward the alpha4beta2 nAChR subtype as compared to the alpha7 and alpha1beta1deltagamma nAChR subtypes. Neuronal nicotinic acetylcholine receptors (nAChRs) modulate the release of several important neurotransmitters, such as acetylcholine and dopamine.

Type
Small Molecule
Groups
Investigational
Structure
Thumb
Weight
Average: 192.2575
Monoisotopic: 192.126263144
Chemical Formula
C11H16N2O
Synonyms
  • Pozanicline
External IDs
  • A-87089.0
  • ABT-089

Pharmacology

Indication

Investigated for use/treatment in Alzheimer's disease, Attention Deficit/Hyperactivity Disorder (ADHD), and Schizophrenia and schizoaffective disorders.

Pharmacology
Reduce drug development failure rates
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Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

ABT-089 is a neuronal nicotinic acetylcholine receptor agonist. Neuronal nicotinic acetylcholine receptors (nAChRs) modulate the release of several important neurotransmitters, such as acetylcholine and dopamine.

Mechanism of action

ABT-089 is a neuronal nicotinic acetylcholine receptor agonist. In radioligand binding studies, ABT-089 has shown selectivity toward the alpha4beta2 nAChR subtype as compared to the alpha7 and alpha1beta1deltagamma nAChR subtypes.

TargetActionsOrganism
UNeuronal acetylcholine receptor subunit alpha-4Not AvailableHumans
UNeuronal acetylcholine receptor subunit beta-2Not AvailableHumans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

ABT-089 was shown to be well-tolerated in clinical trials.

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.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Not Available
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as alkyl aryl ethers. These are organic compounds containing the alkyl aryl ether functional group with the generic formula R-O-R' , where R is an alkyl group and R' is an aryl group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Ethers
Direct Parent
Alkyl aryl ethers
Alternative Parents
Methylpyridines / Pyrrolidines / Heteroaromatic compounds / Dialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Alkyl aryl ether / Amine / Aromatic heteromonocyclic compound / Azacycle / Heteroaromatic compound / Hydrocarbon derivative / Methylpyridine / Organic nitrogen compound / Organoheterocyclic compound / Organonitrogen compound
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
CL2002R563
CAS number
161417-03-4
InChI Key
YRVIKLBSVVNSHF-JTQLQIEISA-N
InChI
InChI=1S/C11H16N2O/c1-9-11(5-3-6-12-9)14-8-10-4-2-7-13-10/h3,5-6,10,13H,2,4,7-8H2,1H3/t10-/m0/s1
IUPAC Name
2-methyl-3-[(2S)-pyrrolidin-2-ylmethoxy]pyridine
SMILES
CC1=C(OC[C@@H]2CCCN2)C=CC=N1

References

General References
  1. Wilens TE, Decker MW: Neuronal nicotinic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: focus on cognition. Biochem Pharmacol. 2007 Oct 15;74(8):1212-23. Epub 2007 Jul 7. [Article]
  2. Rueter LE, Anderson DJ, Briggs CA, Donnelly-Roberts DL, Gintant GA, Gopalakrishnan M, Lin NH, Osinski MA, Reinhart GA, Buckley MJ, Martin RL, McDermott JS, Preusser LC, Seifert TR, Su Z, Cox BF, Decker MW, Sullivan JP: ABT-089: pharmacological properties of a neuronal nicotinic acetylcholine receptor agonist for the potential treatment of cognitive disorders. CNS Drug Rev. 2004 Summer;10(2):167-82. [Article]
PubChem Compound
178052
PubChem Substance
175427009
ChemSpider
155000
BindingDB
50056147
ChEMBL
CHEMBL127071
ZINC
ZINC000000006562
Wikipedia
Pozanicline

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentAttention Deficit Hyperactivity Disorder (ADHD)6
2TerminatedTreatmentAlzheimer's Disease (AD)3
2TerminatedTreatmentAttention Deficit Hyperactivity Disorder (ADHD)1
2TerminatedTreatmentNicotine Addiction1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility13.1 mg/mLALOGPS
logP1.16ALOGPS
logP0.83ChemAxon
logS-1.2ALOGPS
pKa (Strongest Basic)10.47ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area34.15 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity54.89 m3·mol-1ChemAxon
Polarizability21.74 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9938
Blood Brain Barrier+0.9161
Caco-2 permeable-0.5073
P-glycoprotein substrateSubstrate0.5857
P-glycoprotein inhibitor INon-inhibitor0.8356
P-glycoprotein inhibitor IINon-inhibitor0.6084
Renal organic cation transporterInhibitor0.6438
CYP450 2C9 substrateNon-substrate0.8085
CYP450 2D6 substrateNon-substrate0.5074
CYP450 3A4 substrateNon-substrate0.6106
CYP450 1A2 substrateInhibitor0.7961
CYP450 2C9 inhibitorNon-inhibitor0.8086
CYP450 2D6 inhibitorInhibitor0.5756
CYP450 2C19 inhibitorNon-inhibitor0.629
CYP450 3A4 inhibitorNon-inhibitor0.7245
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7095
Ames testNon AMES toxic0.8623
CarcinogenicityNon-carcinogens0.9569
BiodegradationNot ready biodegradable0.9816
Rat acute toxicity2.4195 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5661
hERG inhibition (predictor II)Non-inhibitor0.5535
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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 permeabl...
Gene Name
CHRNA4
Uniprot ID
P43681
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-4
Molecular Weight
69956.47 Da
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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 permeabl...
Gene Name
CHRNB2
Uniprot ID
P17787
Uniprot Name
Neuronal acetylcholine receptor subunit beta-2
Molecular Weight
57018.575 Da

Drug created at November 18, 2007 18:25 / Updated at February 21, 2021 18:51