Huperzine B

Identification

Name
Huperzine B
Accession Number
DB03348  (EXPT01794)
Type
Small Molecule
Groups
Investigational
Description

Huperzine B is a novel acetylcholinesterase inhibitor.

Structure
Thumb
Synonyms
  • HUB
  • HupB
Categories
UNII
Not Available
CAS number
103548-82-9
Weight
Average: 256.3428
Monoisotopic: 256.157563272
Chemical Formula
C16H20N2O
InChI Key
YYWGABLTRMRUIT-HWWQOWPSSA-N
InChI
InChI=1S/C16H20N2O/c1-10-7-11-8-14-13(4-5-15(19)18-14)16(9-10)12(11)3-2-6-17-16/h4-5,7,11-12,17H,2-3,6,8-9H2,1H3,(H,18,19)/t11-,12+,16+/m0/s1
IUPAC Name
(1R,9R,10R)-16-methyl-6,14-diazatetracyclo[7.5.3.0¹,¹⁰.0²,⁷]heptadeca-2(7),3,5,16-tetraen-5-ol
SMILES
[H][[email protected]@]12CC3=C(C=CC(O)=N3)[[email protected]]3(CC(C)=C1)NCCC[[email protected]]23[H]

Pharmacology

Indication

Under investigation for the treatment of Alzheimer's disease.

Structured Indications
Not Available
Pharmacodynamics

Huperzine B is an alkaloid derived from Huperzia serrata (which is available as an herbal product in the US). It is under investigation as an acetylcholinesterase inhibitor. Clinical trials in China have shown that huperzine B is comparably effective to the drugs currently on the market, and may even be somewhat safer in terms of side effects.

Mechanism of action

Huperzine B has been found to be an inhibitor of the enzyme acetylcholinesterase. This is the same mechanism of action of pharmaceutical drugs such as galantamine and donepezil used to treat Alzheimer's disease.

TargetActionsOrganism
UAcetylcholinesteraseNot AvailableHuman
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
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Zhang HY, Tang XC: Huperzine B, a novel acetylcholinesterase inhibitor, attenuates hydrogen peroxide induced injury in PC12 cells. Neurosci Lett. 2000 Sep 29;292(1):41-4. [PubMed:10996445]
  2. Feng S, Xia Y, Han D, Zheng C, He X, Tang X, Bai D: Synthesis and acetylcholinesterase inhibition of derivatives of huperzine B. Bioorg Med Chem Lett. 2005 Feb 1;15(3):523-6. [PubMed:15664805]
  3. He XC, Feng S, Wang ZF, Shi Y, Zheng S, Xia Y, Jiang H, Tang XC, Bai D: Study on dual-site inhibitors of acetylcholinesterase: Highly potent derivatives of bis- and bifunctional huperzine B. Bioorg Med Chem. 2007 Feb 1;15(3):1394-408. Epub 2006 Nov 9. [PubMed:17126020]
External Links
KEGG Compound
C09866
PubChem Compound
5462442
PubChem Substance
175426855
ChemSpider
16744040
BindingDB
50199518
ChEMBL
CHEMBL245079
HET
HUB
PDB Entries
1gpn

Clinical Trials

Clinical Trials
Not Available

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 Solubility0.16 mg/mLALOGPS
logP1.92ALOGPS
logP2.16ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)11.34ChemAxon
pKa (Strongest Basic)9.56ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area45.15 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity75.85 m3·mol-1ChemAxon
Polarizability28.61 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9953
Blood Brain Barrier+0.9465
Caco-2 permeable-0.537
P-glycoprotein substrateSubstrate0.8401
P-glycoprotein inhibitor INon-inhibitor0.6301
P-glycoprotein inhibitor IINon-inhibitor0.8246
Renal organic cation transporterNon-inhibitor0.5913
CYP450 2C9 substrateNon-substrate0.8044
CYP450 2D6 substrateNon-substrate0.7676
CYP450 3A4 substrateSubstrate0.6455
CYP450 1A2 substrateNon-inhibitor0.5655
CYP450 2C9 inhibitorNon-inhibitor0.5898
CYP450 2D6 inhibitorNon-inhibitor0.7528
CYP450 2C19 inhibitorNon-inhibitor0.5068
CYP450 3A4 inhibitorNon-inhibitor0.8313
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5088
Ames testNon AMES toxic0.682
CarcinogenicityNon-carcinogens0.9566
BiodegradationNot ready biodegradable0.9931
Rat acute toxicity2.7113 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9721
hERG inhibition (predictor II)Inhibitor0.5546
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 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

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenanthrolines. These are aromatic polycyclic compounds containing the phenanthroline skeleton, which is a derivative of phenanthrene, and consists of two pyridine rings non-linearly joined by a benzene ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Phenanthrolines
Sub Class
Not Available
Direct Parent
Phenanthrolines
Alternative Parents
Quinolones and derivatives / Pyridinones / Aralkylamines / Piperidines / Heteroaromatic compounds / Lactams / Dialkylamines / Azacyclic compounds / Organooxygen compounds / Organic oxides
show 1 more
Substituents
1,7-phenanthroline / Quinolone / Pyridinone / Aralkylamine / Piperidine / Pyridine / Heteroaromatic compound / Lactam / Secondary aliphatic amine / Azacycle
show 9 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Details
1. Acetylcholinesterase
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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
Uniprot Name
Acetylcholinesterase
Molecular Weight
67795.525 Da
References
  1. He XC, Feng S, Wang ZF, Shi Y, Zheng S, Xia Y, Jiang H, Tang XC, Bai D: Study on dual-site inhibitors of acetylcholinesterase: Highly potent derivatives of bis- and bifunctional huperzine B. Bioorg Med Chem. 2007 Feb 1;15(3):1394-408. Epub 2006 Nov 9. [PubMed:17126020]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 15:12