Natural Product: NPC195919

Natural Product IDNPC195919
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 6,7,3',4'-Tetramethoxyisoflavone
IUPAC Name 3-(3,4-dimethoxyphenyl)-6,7-dimethoxychromen-4-one
Synonyms 3',4',6,7-Tetramethoxyisoflavone; 6,7,3',4'-Tetramethoxyisoflavone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL234932
PubChem CID 631176
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 OYSKBZHHLYECLU-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H18O6/c1-21-14-6-5-11(7-16(14)22-2)13-10-25-15-9-18(24-4)17(23-3)8-12(15)19(13)20/h5-10H,1-4H3
SMILES COc1ccc(cc1OC)c1coc2cc(c(cc2c1=O)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   342.11 Volume:   343.16
?
Van der Waals volume.
Dense:   0.997 LogP:   1.849
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.177
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.371
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   18.0
TPSA:   67.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.707 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.046 Fsp3:   0.211
MCE-18:   18.0
?
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:   0.132 Fluc inhibitor:   0.589
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.866
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.28
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.367 Promiscuous compounds:   0.759

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.623 MDCK Permeability:   -4.635
Pgp-inhibitor:   0.947 Pgp-substrate:   0.164
PAMPA:   0.026
?
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):   0.42
20% Bioavailability (F20%):   0.082 30% Bioavailability (F30%):   0.069
50% Bioavailability (F50%):   0.798

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.854
Plasma Protein Binding (PPB):   88.676% Volume Distribution (VD):   0.229
Fu: 11.961%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.993
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.818
CYP2C19-inhibitor:   0.858 CYP2C19-substrate:   0.785
CYP2C9-inhibitor:   0.443 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.906 CYP2D6-substrate:   0.562
CYP3A4-inhibitor:   0.97 CYP3A4-substrate:   0.297
CYP2B6-substrate:   0.35 CYP2C8-inhibitor:   0.428
HLM stability:   0.187
?
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):  7.153 Half-life (T1/2):  2.112

ADMET: Toxicity

hERG Blockers:  0.208 hERG Blockers (10um):  0.545
Human Hepatotoxicity (H-HT):  0.523 Drug-induced Liver Injury (DILI):  0.796
AMES Toxicity:  0.54 Rat Oral Acute Toxicity:  0.535
Maximum Recommended Daily Dose:  0.614 Skin Sensitization:  0.195
Carcinogencity:  0.825 Eye Corrosion:  0.14
Eye Irritation:  0.928 Respiratory Toxicity:  0.751
Drug-induced Neurotoxicity:  0.653 Ototoxicity:  0.294
Hematotoxicity:  0.455 Drug-induced Nephrotoxicity:  0.395
Genotoxicity:  0.367 RPMI-8226 Immunitoxicity:  0.133
A549 Cytotoxicity:  0.117 Hek293 Cytotoxicity:  0.306
BCF:   1.324
?
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:   3.616
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.518
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.99
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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]
NPO20784 Hibiscus mutabilis Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20717 Pterodon pubescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20784 Hibiscus mutabilis Species Malvaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20784 Hibiscus mutabilis Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20784 Hibiscus mutabilis Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21576 Astropecten aurantiacus Species Astropectinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20784 Hibiscus mutabilis Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3328 Eucalyptus mckieana Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20717 Pterodon pubescens Species Fabaceae 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 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
NPT116 Cell line HL-60 Homo sapiens IC50 = 23000.0 nM PMID[17428663]
NPT393 Cell line HCT-116 Homo sapiens Inhibition = 85.3 % PMID[22456307]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC = 4.0 uM PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 10000.0 nM PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC > 4.0 uM PMID[27100701]
NPT2 Others Unspecified n.a. Ratio = 0.4 n.a. PMID[20829041]

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 NPC195919 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
0.82 Intermediate Similarity NPC148497
0.8085 Intermediate Similarity NPC120924
0.76 Intermediate Similarity NPC185607
0.72 Intermediate Similarity NPC182842
0.6981 Remote Similarity NPC186507
0.6923 Remote Similarity NPC605229
0.6429 Remote Similarity NPC12377
0.6333 Remote Similarity NPC185401
0.6316 Remote Similarity NPC602183
0.625 Remote Similarity NPC471590
0.625 Remote Similarity NPC487217
0.6207 Remote Similarity NPC110086
0.6038 Remote Similarity NPC182428
0.5965 Remote Similarity NPC279061
0.5926 Remote Similarity NPC333230
0.5902 Remote Similarity NPC260640
0.5862 Remote Similarity NPC52623
0.5862 Remote Similarity NPC200316
0.5763 Remote Similarity NPC602689
0.5614 Remote Similarity NPC474340
0.5614 Remote Similarity NPC216314
0.5614 Remote Similarity NPC603503
0.5517 Remote Similarity NPC136095
0.5517 Remote Similarity NPC121522
0.5424 Remote Similarity NPC181209
0.5362 Remote Similarity NPC135345
0.5254 Remote Similarity NPC181124
0.5224 Remote Similarity NPC488570
0.5172 Remote Similarity NPC474264
0.5161 Remote Similarity NPC603384
0.5139 Remote Similarity NPC5840
0.5088 Remote Similarity NPC223354
0.5085 Remote Similarity NPC10467
0.5085 Remote Similarity NPC479067
0.5079 Remote Similarity NPC35544
0.5079 Remote Similarity NPC254741
0.5068 Remote Similarity NPC78071

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC195919 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
0.5085 Remote Similarity NPD2796 Phase 2

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