Natural Product: NPC312843

Natural Product IDNPC312843
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 8-Hydroxygenistein
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002901] Isoflav-2-enes
          • [CHEMONTID:0000494] Isoflavones

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 ZKZCRGBCWBCSNJ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H10O6/c16-8-3-1-7(2-4-8)9-6-21-15-12(13(9)19)10(17)5-11(18)14(15)20/h1-6,16-18,20H
SMILES OC1=CC=C(C=C1)C1=COC2=C(O)C(O)=CC(O)=C2C1=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   286.05 Volume:   273.977
?
Van der Waals volume.
Dense:   1.044 LogP:   1.639
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.842
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.546
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   111.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.403 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.494 Fsp3:   0.0
MCE-18:   18.0
?
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:   0.828 Fluc inhibitor:   0.671
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.89
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.353
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.743 Promiscuous compounds:   0.92

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.392 MDCK Permeability:   -4.818
Pgp-inhibitor:   0.001 Pgp-substrate:   0.052
PAMPA:   0.971
?
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):   0.019
20% Bioavailability (F20%):   0.735 30% Bioavailability (F30%):   0.901
50% Bioavailability (F50%):   0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.014 MRP1:   0.765
Plasma Protein Binding (PPB):   97.571% Volume Distribution (VD):   -0.653
Fu: 2.205%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.737
OATP1B3 inhibitor:   0.805 BCRP inhibitor:   0.8
BSEP inhibitor:   0.118

ADMET: Metabolism

CYP1A2-inhibitor:   0.934 CYP1A2-substrate:   0.316
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.134
CYP2C9-inhibitor:   0.315 CYP2C9-substrate:   0.865
CYP2D6-inhibitor:   0.981 CYP2D6-substrate:   0.607
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.743
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.892
HLM stability:   0.006
?
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):  9.855 Half-life (T1/2):  1.579

ADMET: Toxicity

hERG Blockers:  0.077 hERG Blockers (10um):  0.558
Human Hepatotoxicity (H-HT):  0.463 Drug-induced Liver Injury (DILI):  0.626
AMES Toxicity:  0.569 Rat Oral Acute Toxicity:  0.548
Maximum Recommended Daily Dose:  0.698 Skin Sensitization:  0.751
Carcinogencity:  0.498 Eye Corrosion:  0.052
Eye Irritation:  0.988 Respiratory Toxicity:  0.688
Drug-induced Neurotoxicity:  0.076 Ototoxicity:  0.297
Hematotoxicity:  0.072 Drug-induced Nephrotoxicity:  0.081
Genotoxicity:  0.954 RPMI-8226 Immunitoxicity:  0.038
A549 Cytotoxicity:  0.518 Hek293 Cytotoxicity:  0.558
BCF:   1.071
?
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:   3.881
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.527
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.121
?
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
NPO27951 Vigna mungo Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29532 Vigna angularis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19188 Phaseolus lunatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO993 Phaseolus coccineus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27951 Vigna mungo Species Fabaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO29532 Vigna angularis Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO993 Phaseolus coccineus Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO27951 Vigna mungo Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO29532 Vigna angularis Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO19188 Phaseolus lunatus Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO19188 Phaseolus lunatus Species Fabaceae Eukaryota Sprout Seedling n.a. n.a. Database[FooDB]
NPO27951 Vigna mungo Species Fabaceae Eukaryota Sprout Seedling n.a. n.a. Database[FooDB]
NPO993 Phaseolus coccineus Species Fabaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO19188 Phaseolus lunatus Species Fabaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO29532 Vigna angularis Species Fabaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO993 Phaseolus coccineus Species Fabaceae Eukaryota Leaf Diffusate n.a. n.a. Database[FooDB]
NPO19188 Phaseolus lunatus Species Fabaceae Eukaryota Leaf Diffusate n.a. n.a. Database[FooDB]
NPO27951 Vigna mungo Species Fabaceae Eukaryota Leaf Diffusate n.a. n.a. Database[FooDB]
NPO29532 Vigna angularis Species Fabaceae Eukaryota Leaf Diffusate n.a. n.a. Database[FooDB]
NPO19188 Phaseolus lunatus Species Fabaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO993 Phaseolus coccineus Species Fabaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO29532 Vigna angularis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19188 Phaseolus lunatus Species Fabaceae Eukaryota Seeds n.a. Database[Phenol-Explorer]
NPO29532 Vigna angularis Species Fabaceae Eukaryota Seeds n.a. Database[Phenol-Explorer]
NPO993 Phaseolus coccineus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29532 Vigna angularis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29532 Vigna angularis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29532 Vigna angularis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO993 Phaseolus coccineus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19188 Phaseolus lunatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27951 Vigna mungo Species Fabaceae 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
NPO19188 Phaseolus lunatus Other (raw) Leaf 360 360 360 mg/100g Database [DUKE]
NPO19188 Phaseolus lunatus Other (raw) Leaf Diffusate 0.4 0.4 0.4 mg/100g Database [DUKE]
NPO27951 Vigna mungo Other Leaf Diffusate 0.8 0.8 0.8 mg/100g Database [DUKE]
NPO29532 Vigna angularis Other Leaf Diffusate 0.6 0.6 0.6 mg/100g Database [DUKE]
NPO993 Phaseolus coccineus Raw Leaf Diffusate 0.6 0.6 0.6 mg/100g Database [DUKE]

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 NPC312843 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
0.66 Remote Similarity NPC125449
0.66 Remote Similarity NPC39426
0.6038 Remote Similarity NPC38065
0.6 Remote Similarity NPC131266
0.5472 Remote Similarity NPC188074
0.541 Remote Similarity NPC144118
0.537 Remote Similarity NPC218490
0.537 Remote Similarity NPC608554
0.5357 Remote Similarity NPC487222
0.5345 Remote Similarity NPC303644
0.5263 Remote Similarity NPC295384
0.5254 Remote Similarity NPC483565
0.5238 Remote Similarity NPC222298
0.5238 Remote Similarity NPC604003
0.5238 Remote Similarity NPC608523
0.5185 Remote Similarity NPC193792
0.5185 Remote Similarity NPC234560
0.5179 Remote Similarity NPC87545
0.5172 Remote Similarity NPC269451
0.5091 Remote Similarity NPC296197
0.5091 Remote Similarity NPC225731
0.5085 Remote Similarity NPC216769

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC312843 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
0.66 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