Natural Product: NPC216769

Natural Product IDNPC216769
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7-O-Methyltectorigenin
IUPAC Name 5-hydroxy-3-(4-hydroxyphenyl)-6,7-dimethoxychromen-4-one
Synonyms 7-O-Methyltectorigenin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1689286
PubChem CID 5487785
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 JDKYUORVNMYEIK-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O6/c1-21-13-7-12-14(16(20)17(13)22-2)15(19)11(8-23-12)9-3-5-10(18)6-4-9/h3-8,18,20H,1-2H3
SMILES COc1c(OC)cc2c(c1O)c(=O)c(co2)c1ccc(cc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   314.08 Volume:   308.569
?
Van der Waals volume.
Dense:   1.018 LogP:   2.024
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.044
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.922
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   89.13
?
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:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.325 Fsp3:   0.118
MCE-18:   18.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.252 Fluc inhibitor:   0.895
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.861
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.581
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.374 Promiscuous compounds:   0.796

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.078 MDCK Permeability:   -4.785
Pgp-inhibitor:   0.112 Pgp-substrate:   0.165
PAMPA:   0.615
?
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):   0.038
20% Bioavailability (F20%):   0.23 30% Bioavailability (F30%):   0.183
50% Bioavailability (F50%):   0.919

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.098 MRP1:   0.796
Plasma Protein Binding (PPB):   96.398% Volume Distribution (VD):   -0.645
Fu: 3.689%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.898
OATP1B3 inhibitor:   0.913 BCRP inhibitor:   0.665
BSEP inhibitor:   0.81

ADMET: Metabolism

CYP1A2-inhibitor:   0.939 CYP1A2-substrate:   0.553
CYP2C19-inhibitor:   0.02 CYP2C19-substrate:   0.229
CYP2C9-inhibitor:   0.972 CYP2C9-substrate:   0.1
CYP2D6-inhibitor:   0.992 CYP2D6-substrate:   0.708
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.764
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   0.703
HLM stability:   0.023
?
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):  6.322 Half-life (T1/2):  1.043

ADMET: Toxicity

hERG Blockers:  0.147 hERG Blockers (10um):  0.558
Human Hepatotoxicity (H-HT):  0.52 Drug-induced Liver Injury (DILI):  0.652
AMES Toxicity:  0.41 Rat Oral Acute Toxicity:  0.521
Maximum Recommended Daily Dose:  0.565 Skin Sensitization:  0.543
Carcinogencity:  0.655 Eye Corrosion:  0.088
Eye Irritation:  0.96 Respiratory Toxicity:  0.606
Drug-induced Neurotoxicity:  0.545 Ototoxicity:  0.285
Hematotoxicity:  0.216 Drug-induced Nephrotoxicity:  0.24
Genotoxicity:  0.696 RPMI-8226 Immunitoxicity:  0.072
A549 Cytotoxicity:  0.207 Hek293 Cytotoxicity:  0.492
BCF:   1.11
?
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:   3.749
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.575
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.164
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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
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0168-1656(02)00067-6]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[18078747]
NPO21353 Crotalaria lachnophora Species Fabaceae Eukaryota n.a. whole plant n.a. PMID[21265557]
NPO21353 Crotalaria lachnophora Species Fabaceae Eukaryota whole plant Dschang (west region of Cameroon) 2007-SEP PMID[21265557]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[8882438]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25367 Macaranga vedeliana Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15828 Garcinia nervosa Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO25978 Ochrosia sandwicensis Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15828 Garcinia nervosa Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25815 Asparagopsis sandfordiana Species Bonnemaisoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25367 Macaranga vedeliana Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26542 Rubia cordifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21353 Crotalaria lachnophora 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
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae IZ = 7.0 mm PMID[21265557]
NPT19 Organism Escherichia coli Escherichia coli IZ = 9.3 mm PMID[21265557]

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 NPC216769 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
0.7818 Intermediate Similarity NPC285973
0.7222 Intermediate Similarity NPC269451
0.7091 Intermediate Similarity NPC303644
0.7037 Intermediate Similarity NPC605229
0.6765 Remote Similarity NPC205076
0.6491 Remote Similarity NPC181124
0.6207 Remote Similarity NPC162680
0.6207 Remote Similarity NPC100971
0.6129 Remote Similarity NPC62518
0.6094 Remote Similarity NPC219917
0.6034 Remote Similarity NPC131266
0.6034 Remote Similarity NPC7013
0.5932 Remote Similarity NPC245382
0.5833 Remote Similarity NPC483565
0.5763 Remote Similarity NPC116632
0.5763 Remote Similarity NPC35763
0.5758 Remote Similarity NPC168085
0.5714 Remote Similarity NPC39426
0.5692 Remote Similarity NPC97716
0.5692 Remote Similarity NPC295009
0.5625 Remote Similarity NPC225624
0.5574 Remote Similarity NPC250557
0.5556 Remote Similarity NPC114192
0.5526 Remote Similarity NPC48773
0.55 Remote Similarity NPC78341
0.55 Remote Similarity NPC120163
0.55 Remote Similarity NPC101830
0.5455 Remote Similarity NPC226987
0.541 Remote Similarity NPC294409
0.541 Remote Similarity NPC490701
0.5397 Remote Similarity NPC90665
0.5323 Remote Similarity NPC209487
0.5312 Remote Similarity NPC254702
0.5263 Remote Similarity NPC234560
0.5238 Remote Similarity NPC200316
0.5231 Remote Similarity NPC259166
0.5205 Remote Similarity NPC259070
0.5205 Remote Similarity NPC348541
0.5195 Remote Similarity NPC307518
0.5172 Remote Similarity NPC218490
0.5161 Remote Similarity NPC209560
0.5161 Remote Similarity NPC490700
0.5156 Remote Similarity NPC481044
0.5135 Remote Similarity NPC197896
0.5135 Remote Similarity NPC105511
0.5135 Remote Similarity NPC313163
0.5132 Remote Similarity NPC224462
0.5085 Remote Similarity NPC120924
0.5082 Remote Similarity NPC295384
0.5075 Remote Similarity NPC51070

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC216769 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 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