Natural Product: NPC500023

Natural Product IDNPC500023
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3,5,7,3',5'-Pentahydroxy-6,4'-dimethoxyflavone
IUPAC Name 2-(3,5-dihydroxy-4-methoxy-phenyl)-3,5,7-trihydroxy-6-methoxy-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 FYTXEZMPJUVWOR-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O9/c1-24-16-7(18)3-6(4-8(16)19)15-14(23)12(21)11-10(26-15)5-9(20)17(25-2)13(11)22/h3-5,18-20,22-23H,1-2H3
SMILES COC1=C(O)C=C(C2=C(O)C(=O)C3=C(O)C(OC)=C(O)C=C3O2)C=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   362.06 Volume:   334.939
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Van der Waals volume.
Dense:   1.081 LogP:   1.152
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.367
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.869
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   149.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.471 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.858 Fsp3:   0.118
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:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.85 Fluc inhibitor:   0.442
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.901
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.403
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.548 Promiscuous compounds:   0.956

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.458 MDCK Permeability:   -4.844
Pgp-inhibitor:   0.833 Pgp-substrate:   0.381
PAMPA:   0.203
?
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):   0.066
20% Bioavailability (F20%):   0.09 30% Bioavailability (F30%):   0.863
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.704
Plasma Protein Binding (PPB):   94.617% Volume Distribution (VD):   -0.634
Fu: 5.938%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.951
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.959
BSEP inhibitor:   0.224

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.325
CYP2C19-inhibitor:   0.004 CYP2C19-substrate:   0.97
CYP2C9-inhibitor:   0.85 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.995 CYP2D6-substrate:   0.991
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.999
?
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):  3.219 Half-life (T1/2):  1.572

ADMET: Toxicity

hERG Blockers:  0.043 hERG Blockers (10um):  0.458
Human Hepatotoxicity (H-HT):  0.389 Drug-induced Liver Injury (DILI):  0.691
AMES Toxicity:  0.461 Rat Oral Acute Toxicity:  0.457
Maximum Recommended Daily Dose:  0.522 Skin Sensitization:  0.816
Carcinogencity:  0.561 Eye Corrosion:  0.387
Eye Irritation:  0.992 Respiratory Toxicity:  0.766
Drug-induced Neurotoxicity:  0.053 Ototoxicity:  0.178
Hematotoxicity:  0.159 Drug-induced Nephrotoxicity:  0.086
Genotoxicity:  0.626 RPMI-8226 Immunitoxicity:  0.093
A549 Cytotoxicity:  0.458 Hek293 Cytotoxicity:  0.408
BCF:   0.712
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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:   3.288
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.398
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.771
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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
NPO11437 Alluaudia ascendens Species Didiereaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11437 Alluaudia ascendens Species Didiereaceae 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 NPC500023 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
0.8125 Intermediate Similarity NPC26227
0.7959 Intermediate Similarity NPC98661
0.76 Intermediate Similarity NPC44079
0.7451 Intermediate Similarity NPC50403
0.614 Remote Similarity NPC93376
0.5965 Remote Similarity NPC54394
0.5965 Remote Similarity NPC29841
0.5862 Remote Similarity NPC609179
0.5818 Remote Similarity NPC472438
0.5818 Remote Similarity NPC293183
0.5789 Remote Similarity NPC9609
0.5789 Remote Similarity NPC256283
0.5714 Remote Similarity NPC219330
0.569 Remote Similarity NPC200740
0.5614 Remote Similarity NPC100887
0.5614 Remote Similarity NPC163524
0.5614 Remote Similarity NPC605755
0.5517 Remote Similarity NPC49824
0.5439 Remote Similarity NPC203891
0.5439 Remote Similarity NPC241498
0.5439 Remote Similarity NPC284552
0.5439 Remote Similarity NPC123886
0.5439 Remote Similarity NPC266960
0.5439 Remote Similarity NPC156222
0.5439 Remote Similarity NPC152042
0.5424 Remote Similarity NPC115798
0.5424 Remote Similarity NPC255350
0.541 Remote Similarity NPC227192
0.5345 Remote Similarity NPC87125
0.5345 Remote Similarity NPC241838
0.5345 Remote Similarity NPC28274
0.5345 Remote Similarity NPC601901
0.5333 Remote Similarity NPC189179
0.5333 Remote Similarity NPC75215
0.5333 Remote Similarity NPC474520
0.5246 Remote Similarity NPC133953
0.5246 Remote Similarity NPC125062
0.5167 Remote Similarity NPC55205
0.5167 Remote Similarity NPC83508
0.5167 Remote Similarity NPC159103
0.5085 Remote Similarity NPC143799
0.5085 Remote Similarity NPC608038
0.5077 Remote Similarity NPC130955

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC500023 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
0.5424 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