Natural Product: NPC104728

Natural Product IDNPC104728
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3-(1,3-Benzodioxol-5-Yl)-5,7-Dihydroxychromen-4-One
IUPAC Name 3-(1,3-benzodioxol-5-yl)-5,7-dihydroxychromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL591023
PubChem CID 15301053
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 BNFXYMBRFDJYCH-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H10O6/c17-9-4-11(18)15-14(5-9)20-6-10(16(15)19)8-1-2-12-13(3-8)22-7-21-12/h1-6,17-18H,7H2
SMILES Oc1cc(O)c2c(c1)occ(c2=O)c1ccc2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   298.05 Volume:   282.716
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Van der Waals volume.
Dense:   1.054 LogP:   2.579
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.494
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.831
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   22.0
TPSA:   89.13
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.718 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.436 Fsp3:   0.062
MCE-18:   44.471
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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:   0.583 Fluc inhibitor:   0.988
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.926
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.568
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.305 Promiscuous compounds:   0.449

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.055 MDCK Permeability:   -4.787
Pgp-inhibitor:   0.063 Pgp-substrate:   0.071
PAMPA:   0.364
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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):   0.0
20% Bioavailability (F20%):   0.071 30% Bioavailability (F30%):   0.024
50% Bioavailability (F50%):   0.902

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.23 MRP1:   0.435
Plasma Protein Binding (PPB):   96.898% Volume Distribution (VD):   0.05
Fu: 3.819%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.626
OATP1B3 inhibitor:   0.899 BCRP inhibitor:   0.851
BSEP inhibitor:   0.981

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.885
CYP2C19-inhibitor:   0.023 CYP2C19-substrate:   0.129
CYP2C9-inhibitor:   0.984 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.99
CYP2B6-substrate:   0.097 CYP2C8-inhibitor:   0.656
HLM stability:   0.603
?
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):  3.249 Half-life (T1/2):  1.111

ADMET: Toxicity

hERG Blockers:  0.175 hERG Blockers (10um):  0.535
Human Hepatotoxicity (H-HT):  0.517 Drug-induced Liver Injury (DILI):  0.918
AMES Toxicity:  0.7 Rat Oral Acute Toxicity:  0.591
Maximum Recommended Daily Dose:  0.838 Skin Sensitization:  0.335
Carcinogencity:  0.862 Eye Corrosion:  0.029
Eye Irritation:  0.98 Respiratory Toxicity:  0.797
Drug-induced Neurotoxicity:  0.244 Ototoxicity:  0.19
Hematotoxicity:  0.156 Drug-induced Nephrotoxicity:  0.209
Genotoxicity:  0.971 RPMI-8226 Immunitoxicity:  0.093
A549 Cytotoxicity:  0.261 Hek293 Cytotoxicity:  0.644
BCF:   1.193
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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:   3.883
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.867
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.356
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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
NPO8707.1 Pueraria montana var. lobata Varieties Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8707.1 Pueraria montana var. lobata Varieties Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8707.1 Pueraria montana var. lobata Varieties Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8707.1 Pueraria montana var. lobata Varieties 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

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
NPT83 Cell line MCF7 Homo sapiens IC50 = 70000.0 nM PMID[19932969]
NPT134 Cell line SK-BR-3 Homo sapiens IC50 > 100000.0 nM PMID[19932969]

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 NPC104728 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
0.8036 Intermediate Similarity NPC200316
0.7213 Intermediate Similarity NPC167595
0.7069 Intermediate Similarity NPC294409
0.7069 Intermediate Similarity NPC490701
0.7049 Intermediate Similarity NPC35544
0.6923 Remote Similarity NPC479305
0.6897 Remote Similarity NPC78341
0.6721 Remote Similarity NPC194653
0.6613 Remote Similarity NPC254702
0.6613 Remote Similarity NPC603384
0.6452 Remote Similarity NPC481044
0.6393 Remote Similarity NPC239363
0.6316 Remote Similarity NPC39426
0.6316 Remote Similarity NPC608554
0.6308 Remote Similarity NPC260640
0.614 Remote Similarity NPC193792
0.6102 Remote Similarity NPC38065
0.6029 Remote Similarity NPC233918
0.6 Remote Similarity NPC605634
0.5938 Remote Similarity NPC279668
0.5938 Remote Similarity NPC278323
0.5873 Remote Similarity NPC19980
0.5873 Remote Similarity NPC148497
0.5857 Remote Similarity NPC474052
0.5846 Remote Similarity NPC142876
0.5797 Remote Similarity NPC268059
0.5781 Remote Similarity NPC309154
0.5775 Remote Similarity NPC107838
0.5692 Remote Similarity NPC602183
0.5606 Remote Similarity NPC483637
0.5606 Remote Similarity NPC264550
0.5574 Remote Similarity NPC87545
0.5541 Remote Similarity NPC602155
0.5538 Remote Similarity NPC12377
0.5395 Remote Similarity NPC156457
0.5373 Remote Similarity NPC285973
0.5373 Remote Similarity NPC45291
0.5342 Remote Similarity NPC74178
0.5286 Remote Similarity NPC213659
0.5286 Remote Similarity NPC326109
0.5278 Remote Similarity NPC280937
0.5278 Remote Similarity NPC128774
0.5205 Remote Similarity NPC488570
0.5181 Remote Similarity NPC121647
0.5147 Remote Similarity NPC110086
0.5143 Remote Similarity NPC238279
0.5143 Remote Similarity NPC215375
0.5143 Remote Similarity NPC608523
0.5139 Remote Similarity NPC475705
0.5135 Remote Similarity NPC231763
0.5135 Remote Similarity NPC482075
0.5077 Remote Similarity NPC116632
0.5077 Remote Similarity NPC35763
0.5067 Remote Similarity NPC52889

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC104728 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
0.6316 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