Natural Product: NPC189179

Natural Product IDNPC189179
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3,5,3'-Trihydroxy-6,7,8,4'-Tetramethoxyflavone
IUPAC Name 3,5-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-6,7,8-trimethoxychromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL470679
PubChem CID 10000451
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones
          • [CHEMONTID:0001136] Flavonols

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 MSJSUAMCRPCVFM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H18O9/c1-24-10-6-5-8(7-9(10)20)15-14(23)12(21)11-13(22)17(25-2)19(27-4)18(26-3)16(11)28-15/h5-7,20,22-23H,1-4H3
SMILES COc1ccc(cc1O)c1oc2c(OC)c(OC)c(c(c2c(=O)c1O)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   390.1 Volume:   369.531
?
Van der Waals volume.
Dense:   1.056 LogP:   1.698
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.834
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.399
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   18.0
TPSA:   127.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.602 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.683 Fsp3:   0.211
MCE-18:   21.0
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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:   1 PAINS Alert:   0
Colloidal aggregators:   0.298 Fluc inhibitor:   0.388
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.717
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.449
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.333 Promiscuous compounds:   0.777

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.349 MDCK Permeability:   -4.852
Pgp-inhibitor:   0.413 Pgp-substrate:   0.055
PAMPA:   0.206
?
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):   0.064
20% Bioavailability (F20%):   0.19 30% Bioavailability (F30%):   0.659
50% Bioavailability (F50%):   0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.011 MRP1:   0.975
Plasma Protein Binding (PPB):   97.496% Volume Distribution (VD):   -0.658
Fu: 2.521%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.919
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.94
BSEP inhibitor:   0.568

ADMET: Metabolism

CYP1A2-inhibitor:   0.597 CYP1A2-substrate:   0.144
CYP2C19-inhibitor:   0.054 CYP2C19-substrate:   0.67
CYP2C9-inhibitor:   0.944 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.733 CYP2D6-substrate:   0.193
CYP3A4-inhibitor:   0.976 CYP3A4-substrate:   0.366
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.962
HLM stability:   0.903
?
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):  4.311 Half-life (T1/2):  1.767

ADMET: Toxicity

hERG Blockers:  0.085 hERG Blockers (10um):  0.501
Human Hepatotoxicity (H-HT):  0.437 Drug-induced Liver Injury (DILI):  0.769
AMES Toxicity:  0.349 Rat Oral Acute Toxicity:  0.407
Maximum Recommended Daily Dose:  0.373 Skin Sensitization:  0.68
Carcinogencity:  0.695 Eye Corrosion:  0.213
Eye Irritation:  0.928 Respiratory Toxicity:  0.738
Drug-induced Neurotoxicity:  0.25 Ototoxicity:  0.214
Hematotoxicity:  0.37 Drug-induced Nephrotoxicity:  0.188
Genotoxicity:  0.181 RPMI-8226 Immunitoxicity:  0.144
A549 Cytotoxicity:  0.258 Hek293 Cytotoxicity:  0.357
BCF:   1.002
?
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:   3.514
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.561
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.901
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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
NPO32678 acronychia porteri Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[7964782]
NPO33371 zieridium pseudobtusifolium Species n.a. n.a. n.a. n.a. n.a. PMID[7964782]

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
NPT91 Cell line KB Homo sapiens IC50 = 6.0 ug.mL-1 PMID[18808182]

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 NPC189179 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
0.7818 Intermediate Similarity NPC224137
0.7818 Intermediate Similarity NPC474520
0.7593 Intermediate Similarity NPC608038
0.7193 Intermediate Similarity NPC93376
0.7193 Intermediate Similarity NPC4481
0.7193 Intermediate Similarity NPC196439
0.6441 Remote Similarity NPC200740
0.6441 Remote Similarity NPC54394
0.5833 Remote Similarity NPC176775
0.5833 Remote Similarity NPC143828
0.5806 Remote Similarity NPC75215
0.5806 Remote Similarity NPC235215
0.5806 Remote Similarity NPC7846
0.5806 Remote Similarity NPC2476
0.5738 Remote Similarity NPC49824
0.5738 Remote Similarity NPC86485
0.5714 Remote Similarity NPC482982
0.5645 Remote Similarity NPC55205
0.5574 Remote Similarity NPC201451
0.5556 Remote Similarity NPC25495
0.5556 Remote Similarity NPC160951
0.5522 Remote Similarity NPC130955
0.55 Remote Similarity NPC250822
0.5484 Remote Similarity NPC22472
0.5484 Remote Similarity NPC50715
0.5484 Remote Similarity NPC201136
0.5484 Remote Similarity NPC134677
0.5469 Remote Similarity NPC19687
0.5469 Remote Similarity NPC227325
0.541 Remote Similarity NPC44079
0.541 Remote Similarity NPC292107
0.5385 Remote Similarity NPC227192
0.5323 Remote Similarity NPC301123
0.5323 Remote Similarity NPC105242
0.5323 Remote Similarity NPC231018
0.5312 Remote Similarity NPC603112
0.5238 Remote Similarity NPC9609
0.5238 Remote Similarity NPC256283
0.5224 Remote Similarity NPC259411
0.5161 Remote Similarity NPC98661
0.5156 Remote Similarity NPC204854
0.5156 Remote Similarity NPC183878
0.5156 Remote Similarity NPC82325
0.5156 Remote Similarity NPC270620
0.5156 Remote Similarity NPC146165
0.5079 Remote Similarity NPC50403
0.5079 Remote Similarity NPC241838
0.5077 Remote Similarity NPC52005
0.5077 Remote Similarity NPC223579
0.5077 Remote Similarity NPC609179
0.5077 Remote Similarity NPC610401

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC189179 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