Natural Product: NPC23955

Natural Product IDNPC23955
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3',4',5,6-Tetramethoxy Flavone
IUPAC Name 2-(3,4-dimethoxyphenyl)-5,6-dimethoxychromen-4-one
Synonyms 3',4',5,6-Tetramethoxy Flavone; 5,6,3', 4'-Tetramethoxyflavone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL252339
PubChem CID 14055876
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002591] 6-O-methylated flavonoids

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 KFMFKHCKPGKKNV-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H18O6/c1-21-13-6-5-11(9-17(13)23-3)16-10-12(20)18-14(25-16)7-8-15(22-2)19(18)24-4/h5-10H,1-4H3
SMILES COc1ccc(cc1OC)c1cc(=O)c2c(ccc(c2OC)OC)o1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   342.11 Volume:   343.16
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Van der Waals volume.
Dense:   0.997 LogP:   2.327
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.632
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.393
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   18.0
TPSA:   67.13
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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:   2.128 Fsp3:   0.211
MCE-18:   18.0
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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:   0.086 Fluc inhibitor:   0.787
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.91
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.605
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.362 Promiscuous compounds:   0.572

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.572 MDCK Permeability:   -4.596
Pgp-inhibitor:   0.976 Pgp-substrate:   0.075
PAMPA:   0.016
?
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):   0.172
20% Bioavailability (F20%):   0.192 30% Bioavailability (F30%):   0.217
50% Bioavailability (F50%):   0.965

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.807
Plasma Protein Binding (PPB):   96.262% Volume Distribution (VD):   -0.175
Fu: 3.35%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.97
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.998
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.886 CYP1A2-substrate:   0.996
CYP2C19-inhibitor:   0.228 CYP2C19-substrate:   0.392
CYP2C9-inhibitor:   0.974 CYP2C9-substrate:   0.059
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.988
CYP3A4-inhibitor:   0.923 CYP3A4-substrate:   0.862
CYP2B6-substrate:   0.013 CYP2C8-inhibitor:   0.993
HLM stability:   0.612
?
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):  6.795 Half-life (T1/2):  2.042

ADMET: Toxicity

hERG Blockers:  0.134 hERG Blockers (10um):  0.454
Human Hepatotoxicity (H-HT):  0.447 Drug-induced Liver Injury (DILI):  0.812
AMES Toxicity:  0.557 Rat Oral Acute Toxicity:  0.391
Maximum Recommended Daily Dose:  0.467 Skin Sensitization:  0.421
Carcinogencity:  0.844 Eye Corrosion:  0.71
Eye Irritation:  0.979 Respiratory Toxicity:  0.745
Drug-induced Neurotoxicity:  0.393 Ototoxicity:  0.13
Hematotoxicity:  0.386 Drug-induced Nephrotoxicity:  0.194
Genotoxicity:  0.411 RPMI-8226 Immunitoxicity:  0.086
A549 Cytotoxicity:  0.087 Hek293 Cytotoxicity:  0.342
BCF:   1.754
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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:   3.697
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.601
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.116
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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
NPO10300 Tropaeolum majus Species Tropaeolaceae Eukaryota n.a. flower n.a. DOI[10.1016/j.foodchem.2008.09.013]
NPO10300 Tropaeolum majus Species Tropaeolaceae Eukaryota Flowers São Paulo, Brazil. PMID[32156350]
NPO10300 Tropaeolum majus Species Tropaeolaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10165 Haematomma porphyrium Species Haematommataceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4663 Kopsia profunda Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10300 Tropaeolum majus Species Tropaeolaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10300 Tropaeolum majus Species Tropaeolaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10300 Tropaeolum majus Species Tropaeolaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10300 Tropaeolum majus Species Tropaeolaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4663 Kopsia profunda Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10165 Haematomma porphyrium Species Haematommataceae 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
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 >= 100000.0 nM PMID[17189684]
NPT2 Others Unspecified n.a. IC50 = 25000.0 nM PMID[10096854]

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 NPC23955 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
0.7451 Intermediate Similarity NPC215932
0.6667 Remote Similarity NPC70853
0.6604 Remote Similarity NPC85233
0.6538 Remote Similarity NPC214919
0.6481 Remote Similarity NPC77955
0.6415 Remote Similarity NPC333230
0.6182 Remote Similarity NPC110639
0.6182 Remote Similarity NPC113089
0.614 Remote Similarity NPC255350
0.5862 Remote Similarity NPC69394
0.5818 Remote Similarity NPC14958
0.5763 Remote Similarity NPC283600
0.5763 Remote Similarity NPC195202
0.5763 Remote Similarity NPC12200
0.5763 Remote Similarity NPC604422
0.5741 Remote Similarity NPC302408
0.569 Remote Similarity NPC163780
0.5614 Remote Similarity NPC205522
0.5556 Remote Similarity NPC41721
0.5357 Remote Similarity NPC106461
0.5333 Remote Similarity NPC183597
0.5246 Remote Similarity NPC256612
0.5246 Remote Similarity NPC2476
0.5246 Remote Similarity NPC608258
0.5172 Remote Similarity NPC259058
0.5172 Remote Similarity NPC599976
0.5161 Remote Similarity NPC606105
0.5152 Remote Similarity NPC41853
0.5088 Remote Similarity NPC101294
0.5075 Remote Similarity NPC213622

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC23955 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
0.614 Remote Similarity NPD2801 Pre-clinical
0.5625 Remote Similarity NPD3817 Phase 3

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