Natural Product: NPC120924

Natural Product IDNPC120924
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-(4-Methoxyphenyl)Chromen-4-One
IUPAC Name 6,7-dimethoxy-3-(4-methoxyphenyl)chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL12673
PubChem CID 688655
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 YHXIOAVHEXKZCQ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O5/c1-20-12-6-4-11(5-7-12)14-10-23-15-9-17(22-3)16(21-2)8-13(15)18(14)19/h4-10H,1-3H3
SMILES COc1ccc(cc1)c1coc2cc(c(cc2c1=O)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   312.1 Volume:   317.074
?
Van der Waals volume.
Dense:   0.984 LogP:   2.367
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.665
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.092
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   57.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.738 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.945 Fsp3:   0.167
MCE-18:   17.0
?
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:   0.29 Fluc inhibitor:   0.987
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.917
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.531
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.395 Promiscuous compounds:   0.736

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.616 MDCK Permeability:   -4.61
Pgp-inhibitor:   0.894 Pgp-substrate:   0.062
PAMPA:   0.052
?
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):   0.623
20% Bioavailability (F20%):   0.252 30% Bioavailability (F30%):   0.197
50% Bioavailability (F50%):   0.815

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.663
Plasma Protein Binding (PPB):   87.732% Volume Distribution (VD):   0.036
Fu: 12.727%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.987
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.972
BSEP inhibitor:   0.983

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.163 CYP2C19-substrate:   0.936
CYP2C9-inhibitor:   0.972 CYP2C9-substrate:   0.105
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.391
CYP3A4-inhibitor:   0.009 CYP3A4-substrate:   0.921
CYP2B6-substrate:   0.448 CYP2C8-inhibitor:   1.0
HLM stability:   0.118
?
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):  7.425 Half-life (T1/2):  1.161

ADMET: Toxicity

hERG Blockers:  0.263 hERG Blockers (10um):  0.563
Human Hepatotoxicity (H-HT):  0.511 Drug-induced Liver Injury (DILI):  0.857
AMES Toxicity:  0.584 Rat Oral Acute Toxicity:  0.495
Maximum Recommended Daily Dose:  0.623 Skin Sensitization:  0.195
Carcinogencity:  0.818 Eye Corrosion:  0.136
Eye Irritation:  0.936 Respiratory Toxicity:  0.769
Drug-induced Neurotoxicity:  0.696 Ototoxicity:  0.287
Hematotoxicity:  0.412 Drug-induced Nephrotoxicity:  0.475
Genotoxicity:  0.426 RPMI-8226 Immunitoxicity:  0.112
A549 Cytotoxicity:  0.131 Hek293 Cytotoxicity:  0.326
BCF:   1.294
?
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:   3.842
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.011
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.353
?
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
NPO12418 Myroxylon peruiferum Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/0031-9422(79)80020-5]
NPO12418 Myroxylon peruiferum Species Fabaceae Eukaryota n.a. Brazilian n.a. PMID[10328294]
NPO12418 Myroxylon peruiferum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12418 Myroxylon peruiferum 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

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
NPT451 Organism Helicobacter pylori Helicobacter pylori MIC > 20.0 ug.mL-1 PubChem BioAssay data set
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC = 0.2 uM PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 10000.0 nM PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC > 5.0 uM PMID[27100701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC = 1.0 uM PMID[27100701]

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 NPC120924 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
0.8542 High Similarity NPC186507
0.8085 Intermediate Similarity NPC195919
0.75 Intermediate Similarity NPC182428
0.74 Intermediate Similarity NPC605229
0.7308 Intermediate Similarity NPC148497
0.6923 Remote Similarity NPC474340
0.6923 Remote Similarity NPC603503
0.6792 Remote Similarity NPC136095
0.6792 Remote Similarity NPC121522
0.6667 Remote Similarity NPC182842
0.6415 Remote Similarity NPC185607
0.6415 Remote Similarity NPC474264
0.6406 Remote Similarity NPC135345
0.6364 Remote Similarity NPC487217
0.6346 Remote Similarity NPC223354
0.6296 Remote Similarity NPC10467
0.6207 Remote Similarity NPC254741
0.6182 Remote Similarity NPC209560
0.6182 Remote Similarity NPC490700
0.614 Remote Similarity NPC220050
0.6 Remote Similarity NPC116632
0.5902 Remote Similarity NPC488135
0.5893 Remote Similarity NPC181124
0.5893 Remote Similarity NPC610981
0.5862 Remote Similarity NPC602183
0.5789 Remote Similarity NPC279061
0.5714 Remote Similarity NPC35763
0.5714 Remote Similarity NPC479067
0.5714 Remote Similarity NPC333691
0.569 Remote Similarity NPC52623
0.5614 Remote Similarity NPC69430
0.5614 Remote Similarity NPC124714
0.5614 Remote Similarity NPC294409
0.5614 Remote Similarity NPC490701
0.5517 Remote Similarity NPC181209
0.5517 Remote Similarity NPC471590
0.5441 Remote Similarity NPC45165
0.5439 Remote Similarity NPC216314
0.5397 Remote Similarity NPC185401
0.5345 Remote Similarity NPC100971
0.5323 Remote Similarity NPC13967
0.5323 Remote Similarity NPC606446
0.5238 Remote Similarity NPC260640
0.5179 Remote Similarity NPC608360
0.5167 Remote Similarity NPC12377
0.5161 Remote Similarity NPC478987
0.5143 Remote Similarity NPC259070
0.5143 Remote Similarity NPC478528
0.5085 Remote Similarity NPC216769
0.5082 Remote Similarity NPC100263
0.5079 Remote Similarity NPC607923
0.5077 Remote Similarity NPC193564
0.5077 Remote Similarity NPC133400
0.5072 Remote Similarity NPC487214
0.507 Remote Similarity NPC105511

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC120924 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
0.5714 Remote Similarity NPD2796 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