Natural Product: NPC593204

Natural Product IDNPC593204
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5,7,4'-Trihydroxy-3,6,3',5'-tetramethoxyflavone
IUPAC Name 5,7-dihydroxy-2-(4-hydroxy-3,5-dimethoxy-phenyl)-3,6-dimethoxy-chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 PIAAUDYNDVKPCW-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H18O9/c1-24-11-5-8(6-12(25-2)14(11)21)17-19(27-4)16(23)13-10(28-17)7-9(20)18(26-3)15(13)22/h5-7,20-22H,1-4H3
SMILES COC1=CC(C2=C(OC)C(=O)C3=C(O)C(OC)=C(O)C=C3O2)=CC(OC)=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   390.1 Volume:   369.531
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Van der Waals volume.
Dense:   1.056 LogP:   1.904
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.009
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.471
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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
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.632 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:   0.379 Fluc inhibitor:   0.315
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.832
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.576
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.384 Promiscuous compounds:   0.783

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.262 MDCK Permeability:   -4.813
Pgp-inhibitor:   0.983 Pgp-substrate:   0.147
PAMPA:   0.011
?
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):   0.054
20% Bioavailability (F20%):   0.014 30% Bioavailability (F30%):   0.132
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.011 MRP1:   0.934
Plasma Protein Binding (PPB):   96.327% Volume Distribution (VD):   -0.538
Fu: 3.669%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.96
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.995
BSEP inhibitor:   0.979

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.417
CYP2C19-inhibitor:   0.354 CYP2C19-substrate:   0.606
CYP2C9-inhibitor:   0.355 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.989 CYP2D6-substrate:   0.989
CYP3A4-inhibitor:   0.004 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.987
HLM stability:   0.969
?
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):  3.538 Half-life (T1/2):  1.484

ADMET: Toxicity

hERG Blockers:  0.061 hERG Blockers (10um):  0.471
Human Hepatotoxicity (H-HT):  0.401 Drug-induced Liver Injury (DILI):  0.569
AMES Toxicity:  0.386 Rat Oral Acute Toxicity:  0.379
Maximum Recommended Daily Dose:  0.436 Skin Sensitization:  0.665
Carcinogencity:  0.721 Eye Corrosion:  0.445
Eye Irritation:  0.972 Respiratory Toxicity:  0.674
Drug-induced Neurotoxicity:  0.178 Ototoxicity:  0.189
Hematotoxicity:  0.267 Drug-induced Nephrotoxicity:  0.13
Genotoxicity:  0.293 RPMI-8226 Immunitoxicity:  0.114
A549 Cytotoxicity:  0.234 Hek293 Cytotoxicity:  0.392
BCF:   0.989
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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:   3.525
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.303
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.868
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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
NPO28927 Gutierrezia microcephala Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[3655803]
NPO9607 Tillandsia usneoides Species Bromeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28927 Gutierrezia microcephala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28927 Gutierrezia microcephala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28927 Gutierrezia microcephala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[Title]
NPO28927 Gutierrezia microcephala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9607 Tillandsia usneoides Species Bromeliaceae 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

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 NPC593204 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
0.8163 Intermediate Similarity NPC472438
0.7358 Intermediate Similarity NPC9609
0.7308 Intermediate Similarity NPC203891
0.7308 Intermediate Similarity NPC266960
0.7222 Intermediate Similarity NPC115798
0.7222 Intermediate Similarity NPC29841
0.717 Intermediate Similarity NPC163524
0.6981 Remote Similarity NPC284552
0.6333 Remote Similarity NPC246478
0.5965 Remote Similarity NPC610359
0.5893 Remote Similarity NPC607530
0.5833 Remote Similarity NPC261004
0.5833 Remote Similarity NPC279989
0.5789 Remote Similarity NPC123886
0.5763 Remote Similarity NPC83508
0.5758 Remote Similarity NPC470459
0.5667 Remote Similarity NPC288669
0.5614 Remote Similarity NPC7973
0.5588 Remote Similarity NPC158761
0.5507 Remote Similarity NPC470457
0.55 Remote Similarity NPC82325
0.5493 Remote Similarity NPC470462
0.5424 Remote Similarity NPC76376
0.5417 Remote Similarity NPC470456
0.541 Remote Similarity NPC25495
0.541 Remote Similarity NPC18607
0.541 Remote Similarity NPC162351
0.5405 Remote Similarity NPC101026
0.5405 Remote Similarity NPC488077
0.5345 Remote Similarity NPC293183
0.5345 Remote Similarity NPC26227
0.5333 Remote Similarity NPC256283
0.5323 Remote Similarity NPC78326
0.5254 Remote Similarity NPC241498
0.5254 Remote Similarity NPC44079
0.5254 Remote Similarity NPC98661
0.5254 Remote Similarity NPC184536
0.5254 Remote Similarity NPC156222
0.5254 Remote Similarity NPC103342
0.5246 Remote Similarity NPC204854
0.5246 Remote Similarity NPC176300
0.5246 Remote Similarity NPC255350
0.5205 Remote Similarity NPC603655
0.5179 Remote Similarity NPC181250
0.5167 Remote Similarity NPC100887
0.5167 Remote Similarity NPC286342
0.5167 Remote Similarity NPC214138
0.5167 Remote Similarity NPC59951
0.5167 Remote Similarity NPC110070
0.5167 Remote Similarity NPC28274
0.5167 Remote Similarity NPC120464
0.5167 Remote Similarity NPC101830
0.5161 Remote Similarity NPC78302
0.5161 Remote Similarity NPC58382
0.5161 Remote Similarity NPC236223
0.5161 Remote Similarity NPC603596
0.5082 Remote Similarity NPC18772
0.5079 Remote Similarity NPC19687

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC593204 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
0.5246 Remote Similarity NPD2801 Pre-clinical

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