Natural Product: NPC563908

Natural Product IDNPC563908
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3',4',5,7-Tetrahydroxy-8-methoxyisoflavone
IUPAC Name 3-(3,4-dihydroxyphenyl)-5,7-dihydroxy-8-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 LOPIYUZMSJFIQA-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O7/c1-22-15-12(20)5-11(19)13-14(21)8(6-23-16(13)15)7-2-3-9(17)10(18)4-7/h2-6,17-20H,1H3
SMILES COC1=C(O)C=C(O)C2=C1OC=C(C1=CC=C(O)C(O)=C1)C2=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.06 Volume:   300.063
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Van der Waals volume.
Dense:   1.053 LogP:   1.287
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.516
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.253
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   120.36
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.535 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.651 Fsp3:   0.062
MCE-18:   19.0
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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:   1
Colloidal aggregators:   0.722 Fluc inhibitor:   0.424
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.964
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.483
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.506 Promiscuous compounds:   0.861

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.168 MDCK Permeability:   -4.82
Pgp-inhibitor:   0.002 Pgp-substrate:   0.094
PAMPA:   0.619
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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):   0.021
20% Bioavailability (F20%):   0.852 30% Bioavailability (F30%):   0.967
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.039 MRP1:   0.803
Plasma Protein Binding (PPB):   96.707% Volume Distribution (VD):   -0.566
Fu: 2.913%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.854
OATP1B3 inhibitor:   0.971 BCRP inhibitor:   0.917
BSEP inhibitor:   0.1

ADMET: Metabolism

CYP1A2-inhibitor:   0.126 CYP1A2-substrate:   0.006
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.051 CYP2C9-substrate:   0.005
CYP2D6-inhibitor:   0.293 CYP2D6-substrate:   0.326
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.574
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.676
HLM stability:   0.176
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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):  6.123 Half-life (T1/2):  1.755

ADMET: Toxicity

hERG Blockers:  0.073 hERG Blockers (10um):  0.614
Human Hepatotoxicity (H-HT):  0.435 Drug-induced Liver Injury (DILI):  0.762
AMES Toxicity:  0.588 Rat Oral Acute Toxicity:  0.518
Maximum Recommended Daily Dose:  0.673 Skin Sensitization:  0.904
Carcinogencity:  0.516 Eye Corrosion:  0.031
Eye Irritation:  0.978 Respiratory Toxicity:  0.703
Drug-induced Neurotoxicity:  0.048 Ototoxicity:  0.433
Hematotoxicity:  0.094 Drug-induced Nephrotoxicity:  0.088
Genotoxicity:  0.859 RPMI-8226 Immunitoxicity:  0.05
A549 Cytotoxicity:  0.74 Hek293 Cytotoxicity:  0.416
BCF:   1.118
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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:   3.679
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.471
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.045
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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
NPO58525 Stemphilium sp. No. 644 n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO64318 Streptomyces griseosproeus Genus Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]

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 NPC563908 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
0.8235 Intermediate Similarity NPC131266
0.6786 Remote Similarity NPC245382
0.6364 Remote Similarity NPC38065
0.5902 Remote Similarity NPC194653
0.5806 Remote Similarity NPC254702
0.5738 Remote Similarity NPC264289
0.55 Remote Similarity NPC269451
0.541 Remote Similarity NPC69430
0.541 Remote Similarity NPC294409
0.541 Remote Similarity NPC490701
0.5397 Remote Similarity NPC481044
0.5385 Remote Similarity NPC38545
0.5323 Remote Similarity NPC209487
0.5246 Remote Similarity NPC78341
0.5246 Remote Similarity NPC176665
0.5246 Remote Similarity NPC188203
0.5238 Remote Similarity NPC200316
0.5224 Remote Similarity NPC606794
0.5172 Remote Similarity NPC39426
0.5161 Remote Similarity NPC303644
0.5085 Remote Similarity NPC242893
0.5079 Remote Similarity NPC239363
0.5077 Remote Similarity NPC483637
0.5077 Remote Similarity NPC264550
0.5077 Remote Similarity NPC114192
0.5072 Remote Similarity NPC611071

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC563908 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
0.5172 Remote Similarity NPD1510 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