Natural Product: NPC279061

Natural Product IDNPC279061
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 6,7-Dimethoxy-3-(6-Methoxy-1,3-Benzodioxol-5-Yl)Chromen-4-One
IUPAC Name 6,7-dimethoxy-3-(6-methoxy-1,3-benzodioxol-5-yl)chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL234717
PubChem CID 6728947
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002602] 7-O-methylated isoflavonoids
            • [CHEMONTID:0002689] 7-O-methylisoflavones

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 INHRJYBOMHQVBR-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H16O7/c1-21-13-6-18-17(25-9-26-18)4-10(13)12-8-24-14-7-16(23-3)15(22-2)5-11(14)19(12)20/h4-8H,9H2,1-3H3
SMILES COc1cc2c(cc1c1coc3cc(c(cc3c1=O)OC)OC)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.09 Volume:   343.394
?
Van der Waals volume.
Dense:   1.037 LogP:   2.073
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.328
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.536
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   22.0
TPSA:   76.36
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.71 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.356 Fsp3:   0.211
MCE-18:   45.913
?
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:   0.182 Fluc inhibitor:   0.313
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.85
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.157
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.328 Promiscuous compounds:   0.484

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.778 MDCK Permeability:   -4.688
Pgp-inhibitor:   0.921 Pgp-substrate:   0.026
PAMPA:   0.013
?
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):   0.047
20% Bioavailability (F20%):   0.033 30% Bioavailability (F30%):   0.002
50% Bioavailability (F50%):   0.485

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.006 MRP1:   0.531
Plasma Protein Binding (PPB):   86.722% Volume Distribution (VD):   0.103
Fu: 13.037%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.989
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.963
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.946
CYP2C19-inhibitor:   0.946 CYP2C19-substrate:   0.235
CYP2C9-inhibitor:   0.917 CYP2C9-substrate:   0.603
CYP2D6-inhibitor:   0.988 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.291 CYP3A4-substrate:   0.798
CYP2B6-substrate:   0.517 CYP2C8-inhibitor:   0.021
HLM stability:   0.207
?
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):  5.252 Half-life (T1/2):  1.597

ADMET: Toxicity

hERG Blockers:  0.219 hERG Blockers (10um):  0.512
Human Hepatotoxicity (H-HT):  0.582 Drug-induced Liver Injury (DILI):  0.909
AMES Toxicity:  0.623 Rat Oral Acute Toxicity:  0.557
Maximum Recommended Daily Dose:  0.789 Skin Sensitization:  0.118
Carcinogencity:  0.919 Eye Corrosion:  0.031
Eye Irritation:  0.88 Respiratory Toxicity:  0.709
Drug-induced Neurotoxicity:  0.61 Ototoxicity:  0.279
Hematotoxicity:  0.526 Drug-induced Nephrotoxicity:  0.444
Genotoxicity:  0.782 RPMI-8226 Immunitoxicity:  0.178
A549 Cytotoxicity:  0.154 Hek293 Cytotoxicity:  0.42
BCF:   1.392
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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:   3.556
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.783
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.106
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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
NPO20737 Centaurium cachanlahuen Species Gentianaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/BF01972262]
NPO32819 ateleia glazioviana Species Fabaceae Eukaryota leaves n.a. n.a. PMID[17428663]
NPO20031 Erythrina velutina Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19026536]
NPO20717 Pterodon pubescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20784 Hibiscus mutabilis Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23137 Ulex nanus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22850 Gelasinospora longispora Species Sordariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20031 Erythrina velutina Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22341 Brunsvigia rosea Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20784 Hibiscus mutabilis Species Malvaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23137 Ulex nanus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23137 Ulex nanus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20784 Hibiscus mutabilis Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20784 Hibiscus mutabilis Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23373 Ulmus macrocarpa Species Ulmaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24194 Baccharis intermixta Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24368 Helianthus gracilentus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3184 Circinaria calcarea Species Megasporaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22850 Gelasinospora longispora Species Sordariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23137 Ulex nanus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20717 Pterodon pubescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21576 Astropecten aurantiacus Species Astropectinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23130 Arctostaphylos pumila Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22341 Brunsvigia rosea Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24228 Catocarpus oreites n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO23747 Mildbraediodendron excelsa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26284 Actaea yunnanensis Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24017 Zieria aspalathoides Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20031 Erythrina velutina Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20737 Centaurium cachanlahuen Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23373 Ulmus macrocarpa Species Ulmaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23419 Callitropsis araucarioides Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3328 Eucalyptus mckieana Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20784 Hibiscus mutabilis Species Malvaceae 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
NPT116 Cell line HL-60 Homo sapiens IC50 = 16000.0 nM PMID[17428663]
NPT1171 Cell line HEp-2 Homo sapiens CC50 n.a. n.a. n.a. PMID[38579352]
NPT28912 Organism Human orthopneumovirus Human orthopneumovirus IC50 n.a. n.a. n.a. PMID[38579352]

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 NPC279061 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
0.82 Intermediate Similarity NPC182842
0.7679 Intermediate Similarity NPC153008
0.7321 Intermediate Similarity NPC52623
0.7143 Intermediate Similarity NPC148497
0.6721 Remote Similarity NPC215375
0.6515 Remote Similarity NPC607700
0.629 Remote Similarity NPC167595
0.6207 Remote Similarity NPC216314
0.5965 Remote Similarity NPC195919
0.5942 Remote Similarity NPC18284
0.5902 Remote Similarity NPC65846
0.5789 Remote Similarity NPC120924
0.5625 Remote Similarity NPC478213
0.5571 Remote Similarity NPC273021
0.5556 Remote Similarity NPC602183
0.55 Remote Similarity NPC605229
0.5397 Remote Similarity NPC262623
0.5323 Remote Similarity NPC186507
0.5238 Remote Similarity NPC487217
0.5224 Remote Similarity NPC260640
0.5079 Remote Similarity NPC57211

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC279061 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
NPD

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