Natural Product: NPC52623

Natural Product IDNPC52623
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Glaziovianin A
IUPAC Name 3-(4,7-dimethoxy-1,3-benzodioxol-5-yl)-6,7-dimethoxychromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL234716
PubChem CID 16747686
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002602] 7-O-methylated isoflavonoids
            • [CHEMONTID:0002689] 7-O-methylisoflavones

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey GUSKXWBKZXULSP-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H18O8/c1-22-14-6-11-13(7-15(14)23-2)26-8-12(17(11)21)10-5-16(24-3)19-20(18(10)25-4)28-9-27-19/h5-8H,9H2,1-4H3
SMILES COc1cc2c(cc1OC)occ(c1cc(c3c(c1OC)OCO3)OC)c2=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   386.1 Volume:   369.48
?
Van der Waals volume.
Dense:   1.045 LogP:   1.817
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.14
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.071
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   22.0
TPSA:   85.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.661 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.613 Fsp3:   0.25
MCE-18:   47.84
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.056 Fluc inhibitor:   0.21
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.763
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.246
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.324 Promiscuous compounds:   0.377

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.745 MDCK Permeability:   -4.673
Pgp-inhibitor:   0.962 Pgp-substrate:   0.024
PAMPA:   0.01
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.021
20% Bioavailability (F20%):   0.017 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.455

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.009 MRP1:   0.748
Plasma Protein Binding (PPB):   79.226% Volume Distribution (VD):   0.025
Fu: 17.239%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.794
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.836
CYP2C19-inhibitor:   0.866 CYP2C19-substrate:   0.175
CYP2C9-inhibitor:   0.666 CYP2C9-substrate:   0.015
CYP2D6-inhibitor:   0.835 CYP2D6-substrate:   0.953
CYP3A4-inhibitor:   0.941 CYP3A4-substrate:   0.219
CYP2B6-substrate:   0.312 CYP2C8-inhibitor:   0.338
HLM stability:   0.312
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  4.454 Half-life (T1/2):  1.623

ADMET: Toxicity

hERG Blockers:  0.19 hERG Blockers (10um):  0.535
Human Hepatotoxicity (H-HT):  0.556 Drug-induced Liver Injury (DILI):  0.896
AMES Toxicity:  0.489 Rat Oral Acute Toxicity:  0.515
Maximum Recommended Daily Dose:  0.776 Skin Sensitization:  0.173
Carcinogencity:  0.92 Eye Corrosion:  0.021
Eye Irritation:  0.826 Respiratory Toxicity:  0.647
Drug-induced Neurotoxicity:  0.569 Ototoxicity:  0.303
Hematotoxicity:  0.503 Drug-induced Nephrotoxicity:  0.356
Genotoxicity:  0.591 RPMI-8226 Immunitoxicity:  0.214
A549 Cytotoxicity:  0.144 Hek293 Cytotoxicity:  0.404
BCF:   1.437
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   3.561
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.758
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.057
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO32819 ateleia glazioviana Species Fabaceae Eukaryota leaves n.a. n.a. PMID[17428663]

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 Organism Name 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

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT395 Cell line SF-268 Homo sapiens GI50 = 830.0 nM PMID[17371812]
NPT399 Cell line SF-295 Homo sapiens GI50 = 340.0 nM PMID[17993275]
NPT390 Cell line LOX IMVI Homo sapiens GI50 = 870.0 nM PMID[25316316]
NPT83 Cell line MCF7 Homo sapiens GI50 = 390.0 nM PMID[19966789]
NPT82 Cell line MDA-MB-231 Homo sapiens GI50 = 1100.0 nM PMID[22304344]
NPT380 Cell line U-251 Homo sapiens GI50 = 790.0 nM PMID[22377672]
NPT374 Cell line SF-539 Homo sapiens GI50 = 320.0 nM PMID[12398546]
NPT392 Cell line SNB-75 Homo sapiens GI50 = 630.0 nM PMID[8277309]
NPT578 Cell line SNB-78 Homo sapiens GI50 = 10720.0 nM PMID[10869194]
NPT391 Cell line HCC 2998 Homo sapiens GI50 = 3020.0 nM PMID[8277309]
NPT386 Cell line KM12 Homo sapiens GI50 = 320.0 nM PMID[8691203]
NPT139 Cell line HT-29 Homo sapiens GI50 = 460.0 nM PMID[25856683]
NPT148 Cell line HCT-15 Homo sapiens GI50 = 290.0 nM PMID[8691203]
NPT393 Cell line HCT-116 Homo sapiens GI50 = 560.0 nM PMID[8691203]
NPT370 Cell line NCI-H23 Homo sapiens GI50 = 5130.0 nM PMID[19655762]
NPT455 Cell line NCI-H522 Homo sapiens GI50 = 230.0 nM PMID[19655762]
NPT397 Cell line NCI-H460 Homo sapiens GI50 = 410.0 nM PMID[19576785]
NPT81 Cell line A549 Homo sapiens GI50 = 830.0 nM PubChem BioAssay data set
NPT572 Cell line DMS-273 Homo sapiens GI50 = 130.0 nM PubChem BioAssay data set
NPT576 Cell line DMS-114 Homo sapiens GI50 = 200.0 nM PMID[15568791]
NPT377 Cell line OVCAR-3 Homo sapiens GI50 = 130.0 nM PMID[19081259]
NPT456 Cell line OVCAR-4 Homo sapiens GI50 = 10470.0 nM PMID[11087599]
NPT382 Cell line OVCAR-5 Homo sapiens GI50 = 2190.0 nM PMID[3210015]
NPT381 Cell line OVCAR-8 Homo sapiens GI50 = 1510.0 nM PMID[26231157]
NPT146 Cell line SK-OV-3 Homo sapiens GI50 = 280.0 nM PMID[26231157]
NPT369 Cell line ACHN Homo sapiens GI50 = 620.0 nM PMID[22409377]
NPT2722 Cell line St-4 Homo sapiens GI50 = 15140.0 nM PMID[26920799]
NPT2398 Cell line MKN-7 Homo sapiens GI50 = 1510.0 nM PMID[26920799]
NPT1179 Cell line MKN-28 Homo sapiens GI50 = 450.0 nM PMID[26920799]
NPT1097 Cell line MKN-45 Homo sapiens GI50 = 680.0 nM PMID[26920799]
NPT2723 Cell line MKN-74 Homo sapiens GI50 = 390.0 nM PMID[26920799]
NPT90 Cell line DU-145 Homo sapiens GI50 = 590.0 nM PMID[26900657]
NPT306 Cell line PC-3 Homo sapiens GI50 = 100.0 nM PMID[26900657]
NPT116 Cell line HL-60 Homo sapiens IC50 = 290.0 nM PMID[25695368]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 = 1950.0 nM PMID[17428663]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 = 50.0 nM PMID[17428663]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 = 470.0 nM PMID[17428663]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 = 580.0 nM PMID[17428663]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 = 510.0 nM PMID[17428663]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 = 690.0 nM PMID[17428663]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 590.0 nM PMID[20719506]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC = 0.05 uM PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 270.0 nM PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 1100.0 nM PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC = 4.0 uM PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC = 0.5 uM PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 870.0 nM PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 830.0 nM PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 2200.0 nM PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 430.0 nM PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 10000.0 nM PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 690.0 nM PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 610.0 nM PMID[27665177]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

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 toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC52623 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.7719 Intermediate Similarity NPC478213
0.7321 Intermediate Similarity NPC279061
0.6727 Remote Similarity NPC182842
0.6441 Remote Similarity NPC148497
0.5862 Remote Similarity NPC195919
0.569 Remote Similarity NPC120924
0.5625 Remote Similarity NPC153008
0.5484 Remote Similarity NPC57211
0.541 Remote Similarity NPC605229
0.5156 Remote Similarity NPC487217
0.5079 Remote Similarity NPC216314

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC52623 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
NPD

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by 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