Natural Product: NPC278323

Natural Product IDNPC278323
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2'-Methoxybiochanin A
IUPAC Name 3-(2,4-dimethoxyphenyl)-5,7-dihydroxychromen-4-one
Synonyms 2'-Methoxybiochanin A
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1088580
PubChem CID 44257324
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002606] 4'-O-methylated isoflavonoids
            • [CHEMONTID:0002687] 4'-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 PBUHDEMRGWYORH-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O6/c1-21-10-3-4-11(14(7-10)22-2)12-8-23-15-6-9(18)5-13(19)16(15)17(12)20/h3-8,18-19H,1-2H3
SMILES COc1ccc(c2coc3cc(cc(c3c2=O)O)O)c(c1)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   314.08 Volume:   308.569
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Van der Waals volume.
Dense:   1.018 LogP:   2.364
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.337
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.078
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   89.13
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.772 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.327 Fsp3:   0.118
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:   0.29 Fluc inhibitor:   0.837
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.768
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.551
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.399 Promiscuous compounds:   0.851

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.057 MDCK Permeability:   -4.817
Pgp-inhibitor:   0.295 Pgp-substrate:   0.132
PAMPA:   0.021
?
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):   0.023
20% Bioavailability (F20%):   0.136 30% Bioavailability (F30%):   0.515
50% Bioavailability (F50%):   0.954

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.009 MRP1:   0.565
Plasma Protein Binding (PPB):   97.039% Volume Distribution (VD):   -0.028
Fu: 2.432%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.956
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.995
BSEP inhibitor:   0.81

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.961
CYP2C19-inhibitor:   0.705 CYP2C19-substrate:   0.038
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.997
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.559
CYP2B6-substrate:   0.513 CYP2C8-inhibitor:   0.921
HLM stability:   0.781
?
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):  5.658 Half-life (T1/2):  0.953

ADMET: Toxicity

hERG Blockers:  0.204 hERG Blockers (10um):  0.528
Human Hepatotoxicity (H-HT):  0.485 Drug-induced Liver Injury (DILI):  0.906
AMES Toxicity:  0.706 Rat Oral Acute Toxicity:  0.537
Maximum Recommended Daily Dose:  0.829 Skin Sensitization:  0.196
Carcinogencity:  0.845 Eye Corrosion:  0.026
Eye Irritation:  0.98 Respiratory Toxicity:  0.844
Drug-induced Neurotoxicity:  0.238 Ototoxicity:  0.208
Hematotoxicity:  0.159 Drug-induced Nephrotoxicity:  0.229
Genotoxicity:  0.907 RPMI-8226 Immunitoxicity:  0.108
A549 Cytotoxicity:  0.246 Hek293 Cytotoxicity:  0.616
BCF:   1.148
?
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:   3.86
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.559
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.078
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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
NPO14114 Dalbergia parviflora Species Fabaceae Eukaryota heartwood n.a. n.a. PMID[19928832]
NPO14114 Dalbergia parviflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14114 Dalbergia parviflora 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
NPT396 Cell line T47D Homo sapiens Activity = 3.1 uM PMID[18242997]
NPT396 Cell line T47D Homo sapiens Activity = 1.8 uM PMID[17846127]
NPT83 Cell line MCF7 Homo sapiens Activity > 100.0 uM PMID[19114678]
NPT396 Cell line T47D Homo sapiens Activity > 100.0 uM PMID[19114678]
NPT396 Cell line T47D Homo sapiens Activity = 0.4 uM PMID[19114678]
NPT83 Cell line MCF7 Homo sapiens Activity = 19.6 uM PMID[24412339]
NPT83 Cell line MCF7 Homo sapiens Activity = 3.2 uM PMID[19114678]

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 NPC278323 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
0.7636 Intermediate Similarity NPC294409
0.7636 Intermediate Similarity NPC490701
0.75 Intermediate Similarity NPC239363
0.7414 Intermediate Similarity NPC142876
0.7368 Intermediate Similarity NPC309154
0.7241 Intermediate Similarity NPC279668
0.7119 Intermediate Similarity NPC55162
0.6897 Remote Similarity NPC19980
0.6885 Remote Similarity NPC167595
0.6875 Remote Similarity NPC280937
0.6833 Remote Similarity NPC483637
0.678 Remote Similarity NPC200316
0.6667 Remote Similarity NPC194653
0.6552 Remote Similarity NPC78341
0.6364 Remote Similarity NPC479305
0.629 Remote Similarity NPC254702
0.629 Remote Similarity NPC264550
0.6129 Remote Similarity NPC481044
0.6032 Remote Similarity NPC45291
0.597 Remote Similarity NPC233918
0.5965 Remote Similarity NPC39426
0.5965 Remote Similarity NPC608554
0.5938 Remote Similarity NPC104728
0.5789 Remote Similarity NPC193792
0.5763 Remote Similarity NPC87545
0.5763 Remote Similarity NPC38065
0.5556 Remote Similarity NPC605826
0.5507 Remote Similarity NPC268059
0.5493 Remote Similarity NPC303197
0.5484 Remote Similarity NPC116632
0.5484 Remote Similarity NPC35763
0.5484 Remote Similarity NPC241838
0.5429 Remote Similarity NPC128774
0.5362 Remote Similarity NPC249824
0.5362 Remote Similarity NPC133400
0.5333 Remote Similarity NPC156457
0.5303 Remote Similarity NPC101366
0.5278 Remote Similarity NPC231763
0.5278 Remote Similarity NPC482075
0.5278 Remote Similarity NPC107838
0.5238 Remote Similarity NPC59951
0.5238 Remote Similarity NPC231772
0.5231 Remote Similarity NPC262623
0.5195 Remote Similarity NPC138540
0.5156 Remote Similarity NPC303644
0.5156 Remote Similarity NPC209560
0.5156 Remote Similarity NPC490700
0.5152 Remote Similarity NPC90665
0.5139 Remote Similarity NPC474052
0.5135 Remote Similarity NPC474960
0.5075 Remote Similarity NPC200060
0.5075 Remote Similarity NPC476055
0.5072 Remote Similarity NPC203636

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC278323 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
0.5965 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