Natural Product: NPC148497

Natural Product IDNPC148497
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)-6,7-Dimethoxychromen-4-One
IUPAC Name 3-(1,3-benzodioxol-5-yl)-6,7-dimethoxychromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1224369
PubChem CID 15984086
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 ABOSSEFROBUJKH-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H14O6/c1-20-15-6-11-14(7-16(15)21-2)22-8-12(18(11)19)10-3-4-13-17(5-10)24-9-23-13/h3-8H,9H2,1-2H3
SMILES COc1cc2c(cc1OC)occ(c2=O)c1ccc2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   326.08 Volume:   317.308
?
Van der Waals volume.
Dense:   1.028 LogP:   2.321
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.569
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.124
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   22.0
TPSA:   67.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.736 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.204 Fsp3:   0.167
MCE-18:   44.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.262 Fluc inhibitor:   0.894
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.956
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.367
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.316 Promiscuous compounds:   0.49

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.798 MDCK Permeability:   -4.687
Pgp-inhibitor:   0.849 Pgp-substrate:   0.011
PAMPA:   0.068
?
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):   0.009
20% Bioavailability (F20%):   0.03 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.537

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.047 MRP1:   0.637
Plasma Protein Binding (PPB):   96.123% Volume Distribution (VD):   0.139
Fu: 5.078%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.979
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.849
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.979
CYP2C19-inhibitor:   0.611 CYP2C19-substrate:   0.493
CYP2C9-inhibitor:   0.852 CYP2C9-substrate:   0.981
CYP2D6-inhibitor:   0.992 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.053 CYP3A4-substrate:   0.974
CYP2B6-substrate:   0.721 CYP2C8-inhibitor:   0.012
HLM stability:   0.103
?
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):  4.454 Half-life (T1/2):  1.336

ADMET: Toxicity

hERG Blockers:  0.241 hERG Blockers (10um):  0.544
Human Hepatotoxicity (H-HT):  0.559 Drug-induced Liver Injury (DILI):  0.886
AMES Toxicity:  0.629 Rat Oral Acute Toxicity:  0.56
Maximum Recommended Daily Dose:  0.718 Skin Sensitization:  0.184
Carcinogencity:  0.902 Eye Corrosion:  0.062
Eye Irritation:  0.913 Respiratory Toxicity:  0.699
Drug-induced Neurotoxicity:  0.633 Ototoxicity:  0.282
Hematotoxicity:  0.449 Drug-induced Nephrotoxicity:  0.421
Genotoxicity:  0.69 RPMI-8226 Immunitoxicity:  0.141
A549 Cytotoxicity:  0.148 Hek293 Cytotoxicity:  0.397
BCF:   1.332
?
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:   3.736
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.079
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.336
?
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
NPO27819 Nonomuraea turkmeniaca Species Streptosporangiaceae Bacteria n.a. n.a. n.a. PMID[17636954]
NPO26132 Buxus natalensis Species Buxaceae Eukaryota n.a. bark n.a. PMID[20954721]
NPO26132 Buxus natalensis Species Buxaceae Eukaryota n.a. uMhalanga Rocks nature reserve, Durban, South Africa 2007-FEB PMID[20954721]
NPO27442 Hippeastrum morelianum Species Amaryllidaceae Eukaryota n.a. bulb n.a. PMID[21105684]
NPO20249 Antheroporum pierrei Species Fabaceae Eukaryota n.a. leaf n.a. PMID[21452840]
NPO20249 Antheroporum pierrei Species Fabaceae Eukaryota n.a. twig n.a. PMID[21452840]
NPO27843 Lycoris radiata Species Amaryllidaceae Eukaryota n.a. n.a. n.a. PMID[21510636]
NPO27370 Hapsidospora irregularis Species n.a. Eukaryota n.a. n.a. n.a. PMID[28106998]
NPO27819 Nonomuraea turkmeniaca Species Streptosporangiaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO27601 Perna canaliculus Species Mytilidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27370 Hapsidospora irregularis Species n.a. Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28118 Halimeda monile Species Halimedaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27720 Bagarius bagarius Species Sisoridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27843 Lycoris radiata Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27843 Lycoris radiata Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28172 Rheum palaestinum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28172 Rheum palaestinum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27843 Lycoris radiata Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27426 Cassytha melantha Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27843 Lycoris radiata Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27819 Nonomuraea turkmeniaca Species Streptosporangiaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO27426 Cassytha melantha Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27365 Polybia occidentalis Species Vespidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27370 Hapsidospora irregularis Species n.a. Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27601 Perna canaliculus Species Mytilidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26132 Buxus natalensis Species Buxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20249 Antheroporum pierrei Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28118 Halimeda monile Species Halimedaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27503 Scombresox saurus n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO28022 Baccharis genistifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27268 Cryptocarya densiflora Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27843 Lycoris radiata Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28225 Citrus bigaradia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27720 Bagarius bagarius Species Sisoridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27442 Hippeastrum morelianum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20929 Patellaria scruposa Species Patellariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28172 Rheum palaestinum Species Polygonaceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 56200.0 nM PMID[20719506]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Ratio = 0.01 n.a. PMID[20719506]
NPT20987 Cell line HeLa S3 Homo sapiens Ratio IC50 = 0.01 n.a. PMID[22921744]

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 NPC148497 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 NPC195919
0.7818 Intermediate Similarity NPC602183
0.7308 Intermediate Similarity NPC120924
0.7288 Intermediate Similarity NPC260640
0.7143 Intermediate Similarity NPC279061
0.65 Remote Similarity NPC110086
0.65 Remote Similarity NPC603384
0.6441 Remote Similarity NPC52623
0.6393 Remote Similarity NPC35544
0.6379 Remote Similarity NPC186507
0.6316 Remote Similarity NPC185607
0.6316 Remote Similarity NPC605229
0.625 Remote Similarity NPC182842
0.6066 Remote Similarity NPC602689
0.5882 Remote Similarity NPC605424
0.5873 Remote Similarity NPC104728
0.5806 Remote Similarity NPC220050
0.5738 Remote Similarity NPC487217
0.5714 Remote Similarity NPC153008
0.56 Remote Similarity NPC601607
0.5574 Remote Similarity NPC57211
0.5517 Remote Similarity NPC182428
0.5484 Remote Similarity NPC471590
0.5417 Remote Similarity NPC602155
0.5397 Remote Similarity NPC12377
0.5373 Remote Similarity NPC185401
0.5362 Remote Similarity NPC113055
0.5161 Remote Similarity NPC474340
0.5161 Remote Similarity NPC603503
0.5152 Remote Similarity NPC478213
0.5079 Remote Similarity NPC136095
0.5079 Remote Similarity NPC121522
0.5075 Remote Similarity NPC62518

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC148497 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