Structure

Physi-Chem Properties

Molecular Weight:  127.06
Volume:  127.08
LogP:  -2.392
LogD:  -1.273
LogS:  0.145
# Rotatable Bonds:  1
TPSA:  49.33
# H-Bond Aceptor:  3
# H-Bond Donor:  2
# Rings:  1
# Heavy Atoms:  3

MedChem Properties

QED Drug-Likeness Score:  0.521
Synthetic Accessibility Score:  3.038
Fsp3:  0.5
Lipinski Rule-of-5:  Accepted
Pfizer Rule:  Accepted
GSK Rule:  Accepted
BMS Rule:  0
Golden Triangle Rule:  Rejected
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -4.886
MDCK Permeability:  1.0837313311640173e-05
Pgp-inhibitor:  0.0
Pgp-substrate:  0.008
Human Intestinal Absorption (HIA):  0.152
20% Bioavailability (F20%):  0.003
30% Bioavailability (F30%):  0.036

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.055
Plasma Protein Binding (PPB):  16.778331756591797%
Volume Distribution (VD):  1.13
Pgp-substrate:  91.87015533447266%

ADMET: Metabolism

CYP1A2-inhibitor:  0.017
CYP1A2-substrate:  0.095
CYP2C19-inhibitor:  0.035
CYP2C19-substrate:  0.062
CYP2C9-inhibitor:  0.009
CYP2C9-substrate:  0.165
CYP2D6-inhibitor:  0.007
CYP2D6-substrate:  0.272
CYP3A4-inhibitor:  0.003
CYP3A4-substrate:  0.073

ADMET: Excretion

Clearance (CL):  6.574
Half-life (T1/2):  0.736

ADMET: Toxicity

hERG Blockers:  0.024
Human Hepatotoxicity (H-HT):  0.134
Drug-inuced Liver Injury (DILI):  0.032
AMES Toxicity:  0.028
Rat Oral Acute Toxicity:  0.034
Maximum Recommended Daily Dose:  0.451
Skin Sensitization:  0.953
Carcinogencity:  0.058
Eye Corrosion:  0.896
Eye Irritation:  0.907
Respiratory Toxicity:  0.775

Download Data

Data Type Select
General Info & Identifiers & Properties  
Structure MOL file  
Source Organisms  
Biological Activities  
Similar NPs/Drugs  

  Natural Product: NPC4668

Natural Product ID:  NPC4668
Common Name*:   Guvacine
IUPAC Name:   1,2,3,6-tetrahydropyridin-1-ium-5-carboxylate
Synonyms:   Guvacine
Standard InCHIKey:  QTDZOWFRBNTPQR-UHFFFAOYSA-N
Standard InCHI:  InChI=1S/C6H9NO2/c8-6(9)5-2-1-3-7-4-5/h2,7H,1,3-4H2,(H,8,9)
SMILES:  OC(=O)C1=CCCNC1
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL76768
PubChem CID:   40468028
3532
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO3806 Garcinia morella Species Clusiaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0040-4039(00)90246-6]
NPO3912 Areca catechu Species Arecaceae Eukaryota n.a. fruit n.a. Database[Article]
NPO5949 Pericarpium arecae n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO3912 Areca catechu Species Arecaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3806 Garcinia morella Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3806 Garcinia morella Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5949 Pericarpium arecae n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO6483 Semen arecae preparata n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO3912 Areca catechu Species Arecaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3912 Areca catechu Species Arecaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3806 Garcinia morella Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3912 Areca catechu Species Arecaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO3912 Areca catechu Species Arecaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3806 Garcinia morella Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

  NP Quantity Composition/Concentration

Organism ID NP ID Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

  Biological Activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT210 Individual Protein Thyroid stimulating hormone receptor Homo sapiens Potency = 39810.7 nM PMID[559408]
NPT242 Individual Protein Dopamine D1 receptor Homo sapiens Potency n.a. 1458.0 nM PMID[559409]
NPT5 Individual Protein Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Homo sapiens Potency n.a. 891.3 nM PMID[559409]
NPT62 Individual Protein 6-phospho-1-fructokinase Trypanosoma brucei Potency n.a. 37933.0 nM PMID[559409]
NPT135 Individual Protein Chromobox protein homolog 1 Homo sapiens Potency n.a. 5972.8 nM PMID[559409]
NPT104 Individual Protein Cerebroside-sulfatase Homo sapiens Potency n.a. 13.5 nM PMID[559409]
NPT29 Organism Rattus norvegicus Rattus norvegicus IC50 = 4920.0 nM PMID[559400]
NPT805 Protein Complex GABA-A receptor; anion channel Rattus norvegicus Inhibition = 27.0 % PMID[559400]
NPT806 Individual Protein Glutamate decarboxylase 67 kDa isoform Rattus norvegicus Inhibition = 0.0 % PMID[559400]
NPT807 Individual Protein Gamma-amino-N-butyrate transaminase Rattus norvegicus Inhibition = 7.0 % PMID[559400]
NPT29 Organism Rattus norvegicus Rattus norvegicus IC50 = 7300.0 nM PMID[559401]
NPT29 Organism Rattus norvegicus Rattus norvegicus IC50 = 12000.0 nM PMID[559402]
NPT32 Organism Mus musculus Mus musculus IC50 = 32000.0 nM PMID[559402]
NPT32 Organism Mus musculus Mus musculus IC50 = 29000.0 nM PMID[559402]
NPT808 Individual Protein GABA transporter 1 Homo sapiens IC50 = 14000.0 nM PMID[559403]
NPT809 Individual Protein GABA transporter 2 Rattus norvegicus IC50 = 58000.0 nM PMID[559403]
NPT810 Individual Protein GABA transporter 3 Homo sapiens IC50 = 119000.0 nM PMID[559403]
NPT811 Individual Protein Betaine transporter Homo sapiens IC50 = 1870000.0 nM PMID[559403]
NPT812 Individual Protein GABA transporter 1 Rattus norvegicus IC50 = 2650.0 nM PMID[559405]
NPT812 Individual Protein GABA transporter 1 Rattus norvegicus IC50 = 1680.0 nM PMID[559405]
NPT812 Individual Protein GABA transporter 1 Rattus norvegicus IC50 = 2900.0 nM PMID[559405]
NPT812 Individual Protein GABA transporter 1 Rattus norvegicus IC50 = 2260.0 nM PMID[559405]
NPT812 Individual Protein GABA transporter 1 Rattus norvegicus IC50 = 2660.0 nM PMID[559405]
NPT812 Individual Protein GABA transporter 1 Rattus norvegicus IC50 = 1760.0 nM PMID[559405]
NPT812 Individual Protein GABA transporter 1 Rattus norvegicus IC50 = 1870.0 nM PMID[559405]
NPT812 Individual Protein GABA transporter 1 Rattus norvegicus IC50 = 2790.0 nM PMID[559405]
NPT812 Individual Protein GABA transporter 1 Rattus norvegicus IC50 = 1910.0 nM PMID[559405]
NPT812 Individual Protein GABA transporter 1 Rattus norvegicus IC50 = 2770.0 nM PMID[559405]
NPT812 Individual Protein GABA transporter 1 Rattus norvegicus IC50 = 1850.0 nM PMID[559405]
NPT812 Individual Protein GABA transporter 1 Rattus norvegicus IC50 = 2590.0 nM PMID[559405]
NPT812 Individual Protein GABA transporter 1 Rattus norvegicus IC50 = 2560.0 nM PMID[559405]
NPT813 Individual Protein GABA transporter 1 Mus musculus IC50 = 13489.63 nM PMID[559406]
NPT814 Individual Protein GABA transporter 2 Mus musculus IC50 = 489778.82 nM PMID[559406]
NPT815 Individual Protein GABA transporter 3 Mus musculus IC50 = 25703.96 nM PMID[559406]
NPT816 Individual Protein GABA transporter 4 Mus musculus IC50 = 25703.96 nM PMID[559406]
NPT810 Individual Protein GABA transporter 3 Homo sapiens IC50 = 110000.0 nM PMID[559407]
NPT817 Individual Protein GABA transporter 2 Homo sapiens IC50 = 66000.0 nM PMID[559407]
NPT813 Individual Protein GABA transporter 1 Mus musculus IC50 = 12589.25 nM PMID[559411]
NPT813 Individual Protein GABA transporter 1 Mus musculus IC50 = 14000.0 nM PMID[559411]
NPT813 Individual Protein GABA transporter 1 Mus musculus IC50 = 20900.0 nM PMID[559412]
NPT814 Individual Protein GABA transporter 2 Mus musculus IC50 > 1000000.0 nM PMID[559412]
NPT815 Individual Protein GABA transporter 3 Mus musculus IC50 = 72400.0 nM PMID[559412]
NPT816 Individual Protein GABA transporter 4 Mus musculus IC50 = 114800.0 nM PMID[559412]
NPT808 Individual Protein GABA transporter 1 Homo sapiens IC50 = 14000.0 nM PMID[559413]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

  Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

●  The left chart: Distribution of similarity level between NPC4668 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.56 or Top200).

Similarity Score Similarity Level Natural Product ID
1.0 High Similarity NPC133758
0.8906 High Similarity NPC98329
0.8906 High Similarity NPC7392
0.8852 High Similarity NPC305973
0.8594 High Similarity NPC112312
0.7576 Intermediate Similarity NPC14437
0.7576 Intermediate Similarity NPC270412
0.6842 Remote Similarity NPC122471
0.6757 Remote Similarity NPC133700
0.6747 Remote Similarity NPC202056
0.64 Remote Similarity NPC90782
0.6389 Remote Similarity NPC66789
0.5938 Remote Similarity NPC87137
0.5909 Remote Similarity NPC221467
0.5823 Remote Similarity NPC126293
0.5821 Remote Similarity NPC43053
0.5758 Remote Similarity NPC137419
0.5758 Remote Similarity NPC122212
0.5738 Remote Similarity NPC8270
0.5645 Remote Similarity NPC221250
0.5634 Remote Similarity NPC51846
0.5625 Remote Similarity NPC6963
0.5625 Remote Similarity NPC304079
0.56 Remote Similarity NPC77891

  Chemically structural similarity: II. Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC4668 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.8906 High Similarity NPD9137 Approved
0.7576 Intermediate Similarity NPD9418 Clinical (unspecified phase)
0.5876 Remote Similarity NPD2905 Discontinued
0.5823 Remote Similarity NPD9354 Clinical (unspecified phase)
0.5823 Remote Similarity NPD9355 Approved

  Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data