Natural Product: NPC239363

Natural Product IDNPC239363
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7-Demethylrobustigenin
IUPAC Name 5,7-dihydroxy-3-(2,4,5-trimethoxyphenyl)chromen-4-one
Synonyms 7-Demethylrobustigenin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1087519
PubChem CID 7330538
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 JLYUMUHNYLUAKZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O7/c1-22-13-7-15(24-3)14(23-2)6-10(13)11-8-25-16-5-9(19)4-12(20)17(16)18(11)21/h4-8,19-20H,1-3H3
SMILES COc1cc(OC)c(cc1c1coc2c(c1=O)c(O)cc(c2)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   344.09 Volume:   334.655
?
Van der Waals volume.
Dense:   1.028 LogP:   1.907
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.962
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.889
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   98.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.751 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.397 Fsp3:   0.167
MCE-18:   19.0
?
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:   0.234 Fluc inhibitor:   0.28
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.633
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.552
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.357 Promiscuous compounds:   0.835

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.115 MDCK Permeability:   -4.811
Pgp-inhibitor:   0.573 Pgp-substrate:   0.186
PAMPA:   0.004
?
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):   0.013
20% Bioavailability (F20%):   0.074 30% Bioavailability (F30%):   0.323
50% Bioavailability (F50%):   0.959

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.646
Plasma Protein Binding (PPB):   96.135% Volume Distribution (VD):   -0.057
Fu: 3.427%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.989
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.999
BSEP inhibitor:   0.937

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.698
CYP2C19-inhibitor:   0.777 CYP2C19-substrate:   0.107
CYP2C9-inhibitor:   0.986 CYP2C9-substrate:   0.251
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.007 CYP3A4-substrate:   0.108
CYP2B6-substrate:   0.03 CYP2C8-inhibitor:   0.965
HLM stability:   0.915
?
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):  6.292 Half-life (T1/2):  1.468

ADMET: Toxicity

hERG Blockers:  0.132 hERG Blockers (10um):  0.54
Human Hepatotoxicity (H-HT):  0.505 Drug-induced Liver Injury (DILI):  0.862
AMES Toxicity:  0.567 Rat Oral Acute Toxicity:  0.583
Maximum Recommended Daily Dose:  0.852 Skin Sensitization:  0.261
Carcinogencity:  0.795 Eye Corrosion:  0.026
Eye Irritation:  0.976 Respiratory Toxicity:  0.822
Drug-induced Neurotoxicity:  0.206 Ototoxicity:  0.196
Hematotoxicity:  0.171 Drug-induced Nephrotoxicity:  0.136
Genotoxicity:  0.92 RPMI-8226 Immunitoxicity:  0.117
A549 Cytotoxicity:  0.28 Hek293 Cytotoxicity:  0.625
BCF:   1.032
?
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:   3.584
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.382
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.784
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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 > 100.0 uM PMID[17663585]
NPT396 Cell line T47D Homo sapiens Activity = 6.3 uM PMID[19364854]
NPT83 Cell line MCF7 Homo sapiens Activity = 7.8 uM PMID[20614907]
NPT83 Cell line MCF7 Homo sapiens Activity = 5.4 uM PMID[20614907]
NPT396 Cell line T47D Homo sapiens Activity = 0.1 uM PMID[20614907]
NPT83 Cell line MCF7 Homo sapiens Activity > 100.0 uM PMID[20614907]

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 NPC239363 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
0.8364 Intermediate Similarity NPC167595
0.7966 Intermediate Similarity NPC280937
0.7736 Intermediate Similarity NPC78341
0.7636 Intermediate Similarity NPC200316
0.75 Intermediate Similarity NPC278323
0.7455 Intermediate Similarity NPC19980
0.7193 Intermediate Similarity NPC481044
0.7018 Intermediate Similarity NPC262623
0.7018 Intermediate Similarity NPC309154
0.6964 Remote Similarity NPC294409
0.6964 Remote Similarity NPC490701
0.678 Remote Similarity NPC254702
0.678 Remote Similarity NPC142876
0.678 Remote Similarity NPC483637
0.661 Remote Similarity NPC194653
0.6562 Remote Similarity NPC479305
0.6406 Remote Similarity NPC268059
0.6393 Remote Similarity NPC104728
0.6333 Remote Similarity NPC279668
0.6296 Remote Similarity NPC193792
0.623 Remote Similarity NPC264550
0.623 Remote Similarity NPC45291
0.6182 Remote Similarity NPC39426
0.6182 Remote Similarity NPC608554
0.5965 Remote Similarity NPC182842
0.5965 Remote Similarity NPC38065
0.5938 Remote Similarity NPC215375
0.5909 Remote Similarity NPC233918
0.5821 Remote Similarity NPC128774
0.569 Remote Similarity NPC87545
0.5667 Remote Similarity NPC216314
0.5652 Remote Similarity NPC482075
0.5507 Remote Similarity NPC474052
0.5467 Remote Similarity NPC481043
0.5429 Remote Similarity NPC184547
0.5429 Remote Similarity NPC74178
0.5429 Remote Similarity NPC303197
0.541 Remote Similarity NPC131266
0.5397 Remote Similarity NPC65846
0.5352 Remote Similarity NPC52889
0.5238 Remote Similarity NPC250557
0.5231 Remote Similarity NPC55162
0.5231 Remote Similarity NPC476055
0.5224 Remote Similarity NPC238279
0.5211 Remote Similarity NPC107838
0.5161 Remote Similarity NPC269451
0.5156 Remote Similarity NPC12377
0.5147 Remote Similarity NPC213659
0.5147 Remote Similarity NPC326109
0.5079 Remote Similarity NPC303644
0.5079 Remote Similarity NPC609386
0.5075 Remote Similarity NPC93552
0.5068 Remote Similarity NPC474960

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC239363 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
0.6182 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