Natural Product: NPC193792

Natural Product IDNPC193792
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5,7-Dihydroxy-3',5'-Dihydroxyisoflavone
IUPAC Name 3-(3,5-dihydroxyphenyl)-5,7-dihydroxychromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1079734
PubChem CID 46879752
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 XCLBJTYTTUIYQL-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H10O6/c16-8-1-7(2-9(17)3-8)11-6-21-13-5-10(18)4-12(19)14(13)15(11)20/h1-6,16-19H
SMILES Oc1cc(O)cc(c1)c1coc2c(c1=O)c(O)cc(c2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   286.05 Volume:   273.977
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Van der Waals volume.
Dense:   1.044 LogP:   1.206
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.527
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.071
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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:   0.546 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.595 Fsp3:   0.0
MCE-18:   18.0
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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:   0 PAINS Alert:   0
Colloidal aggregators:   0.661 Fluc inhibitor:   0.558
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.856
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.322
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.637 Promiscuous compounds:   0.763

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.239 MDCK Permeability:   -4.807
Pgp-inhibitor:   0.0 Pgp-substrate:   0.468
PAMPA:   0.284
?
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):   0.0
20% Bioavailability (F20%):   0.452 30% Bioavailability (F30%):   0.854
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.009 MRP1:   0.233
Plasma Protein Binding (PPB):   94.544% Volume Distribution (VD):   -0.343
Fu: 7.483%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.807
OATP1B3 inhibitor:   0.901 BCRP inhibitor:   0.91
BSEP inhibitor:   0.093

ADMET: Metabolism

CYP1A2-inhibitor:   0.921 CYP1A2-substrate:   0.555
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.252
CYP2C9-inhibitor:   0.987 CYP2C9-substrate:   0.979
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.423
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.96
?
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):  5.189 Half-life (T1/2):  1.595

ADMET: Toxicity

hERG Blockers:  0.145 hERG Blockers (10um):  0.582
Human Hepatotoxicity (H-HT):  0.497 Drug-induced Liver Injury (DILI):  0.609
AMES Toxicity:  0.613 Rat Oral Acute Toxicity:  0.581
Maximum Recommended Daily Dose:  0.933 Skin Sensitization:  0.646
Carcinogencity:  0.73 Eye Corrosion:  0.055
Eye Irritation:  0.997 Respiratory Toxicity:  0.782
Drug-induced Neurotoxicity:  0.123 Ototoxicity:  0.141
Hematotoxicity:  0.035 Drug-induced Nephrotoxicity:  0.058
Genotoxicity:  0.996 RPMI-8226 Immunitoxicity:  0.063
A549 Cytotoxicity:  0.353 Hek293 Cytotoxicity:  0.864
BCF:   1.244
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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:   3.68
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.422
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.937
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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
NPO6711 Streptomyces mirabilis Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[19818612]
NPO6711 Streptomyces mirabilis Species Streptomycetaceae Bacteria 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
NPT737 Cell line HUVEC Homo sapiens GI50 = 133000.0 nM PMID[18625771]
NPT111 Cell line K562 Homo sapiens GI50 = 75000.0 nM PMID[20625154]
NPT83 Cell line MCF7 Homo sapiens GI50 = 65000.0 nM PMID[18341287]
NPT165 Cell line HeLa Homo sapiens CC50 = 134000.0 nM PMID[19848434]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 > 174000.0 nM PMID[19818612]

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 NPC193792 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
0.766 Intermediate Similarity NPC38065
0.7609 Intermediate Similarity NPC39426
0.7609 Intermediate Similarity NPC608554
0.6863 Remote Similarity NPC78341
0.6731 Remote Similarity NPC294409
0.6731 Remote Similarity NPC490701
0.6667 Remote Similarity NPC194653
0.6667 Remote Similarity NPC481044
0.66 Remote Similarity NPC87545
0.6531 Remote Similarity NPC212767
0.6481 Remote Similarity NPC200316
0.6296 Remote Similarity NPC239363
0.625 Remote Similarity NPC254702
0.6207 Remote Similarity NPC238279
0.614 Remote Similarity NPC104728
0.6 Remote Similarity NPC19980
0.5965 Remote Similarity NPC45291
0.5932 Remote Similarity NPC608523
0.5893 Remote Similarity NPC309154
0.5833 Remote Similarity NPC213659
0.5833 Remote Similarity NPC326109
0.5806 Remote Similarity NPC128774
0.5789 Remote Similarity NPC279668
0.5789 Remote Similarity NPC278323
0.5738 Remote Similarity NPC606200
0.569 Remote Similarity NPC142876
0.569 Remote Similarity NPC483637
0.569 Remote Similarity NPC476055
0.569 Remote Similarity NPC264550
0.5645 Remote Similarity NPC475705
0.5645 Remote Similarity NPC233918
0.5645 Remote Similarity NPC268059
0.5625 Remote Similarity NPC482075
0.5625 Remote Similarity NPC74178
0.5556 Remote Similarity NPC479305
0.5538 Remote Similarity NPC52889
0.5532 Remote Similarity NPC185497
0.55 Remote Similarity NPC93552
0.55 Remote Similarity NPC167595
0.5469 Remote Similarity NPC474052
0.5385 Remote Similarity NPC107838
0.5385 Remote Similarity NPC600495
0.5323 Remote Similarity NPC85131
0.5323 Remote Similarity NPC232947
0.5208 Remote Similarity NPC65060
0.5077 Remote Similarity NPC280937
0.5077 Remote Similarity NPC485109

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC193792 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
0.7609 Intermediate 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