Natural Product: NPC549306

Natural Product IDNPC549306
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Chrysoeriol glucuronide
IUPAC Name (2~{S},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-[5-hydroxy-2-(4-hydroxy-3-methoxy-phenyl)-4-oxo-chromen-7-yl]oxy-tetrahydropyran-2-carboxylic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001111] Flavonoid glycosides
          • [CHEMONTID:0001583] Flavonoid O-glycosides
            • [CHEMONTID:0002934] Flavonoid O-glucuronides
              • [CHEMONTID:0003534] Flavonoid-7-O-glucuronides

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 VLYLVFHVHHGXHX-SXFAUFNYSA-N
Standard InCHI InChI=1S/C22H20O12/c1-31-14-4-8(2-3-10(14)23)13-7-12(25)16-11(24)5-9(6-15(16)33-13)32-22-19(28)17(26)18(27)20(34-22)21(29)30/h2-7,17-20,22-24,26-28H,1H3,(H,29,30)/t17-,18-,19+,20-,22+/m0/s1
SMILES COC1=CC(C2=CC(=O)C3=C(O)C=C(O[C@@H]4O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]4O)C=C3O2)=CC=C1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   476.1 Volume:   436.597
?
Van der Waals volume.
Dense:   1.09 LogP:   1.358
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.533
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.009
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   25.0
TPSA:   196.35
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.292 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.94 Fsp3:   0.273
MCE-18:   90.643
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.449 Fluc inhibitor:   0.345
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.977
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.906
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.106 Promiscuous compounds:   0.389

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.149 MDCK Permeability:   -5.346
Pgp-inhibitor:   0.0 Pgp-substrate:   0.628
PAMPA:   1.0
?
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):   0.188
20% Bioavailability (F20%):   0.09 30% Bioavailability (F30%):   0.401
50% Bioavailability (F50%):   0.963

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.985
Plasma Protein Binding (PPB):   79.06% Volume Distribution (VD):   -0.273
Fu: 16.061%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.84
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.719
BSEP inhibitor:   0.015

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.009 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.097
HLM stability:   0.004
?
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):  1.552 Half-life (T1/2):  4.211

ADMET: Toxicity

hERG Blockers:  0.014 hERG Blockers (10um):  0.067
Human Hepatotoxicity (H-HT):  0.544 Drug-induced Liver Injury (DILI):  0.992
AMES Toxicity:  0.7 Rat Oral Acute Toxicity:  0.065
Maximum Recommended Daily Dose:  0.097 Skin Sensitization:  0.962
Carcinogencity:  0.181 Eye Corrosion:  0.0
Eye Irritation:  0.841 Respiratory Toxicity:  0.123
Drug-induced Neurotoxicity:  0.001 Ototoxicity:  0.713
Hematotoxicity:  0.134 Drug-induced Nephrotoxicity:  0.585
Genotoxicity:  0.965 RPMI-8226 Immunitoxicity:  0.07
A549 Cytotoxicity:  0.063 Hek293 Cytotoxicity:  0.14
BCF:   0.252
?
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:   2.86
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.266
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.391
?
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
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1104/pp.84.1.73]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[12232319]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[22208890]
NPO20874 Tanacetum vulgare Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[25924515]
NPO20874 Tanacetum vulgare Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[37630407]
NPO55669 Artemisia judaica Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[38930948]
NPO19146 Cosmos bipinnatus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO42191 Ajuga iva Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19044 Medicago polymorpha Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20874 Tanacetum vulgare Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO55669 Artemisia judaica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18843 Antirrhinum majus Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28284 Medicago arabica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8970 Citrullus lanatus Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8970 Citrullus lanatus Species Cucurbitaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8970 Citrullus lanatus Species Cucurbitaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO8970 Citrullus lanatus Species Cucurbitaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO20874 Tanacetum vulgare Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18843 Antirrhinum majus Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20874 Tanacetum vulgare Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18843 Antirrhinum majus Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18843 Antirrhinum majus Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8970 Citrullus lanatus Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO18321 Medicago sativa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19044 Medicago polymorpha Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8970 Citrullus lanatus Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19146 Cosmos bipinnatus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18843 Antirrhinum majus Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28284 Medicago arabica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20874 Tanacetum vulgare Species Asteraceae 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

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 NPC549306 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
0.8205 Intermediate Similarity NPC282169
0.8205 Intermediate Similarity NPC20505
0.8101 Intermediate Similarity NPC608742
0.6941 Remote Similarity NPC311830
0.6628 Remote Similarity NPC43211
0.6628 Remote Similarity NPC601144
0.6533 Remote Similarity NPC137062
0.6322 Remote Similarity NPC237435
0.6222 Remote Similarity NPC600989
0.6136 Remote Similarity NPC135277
0.6136 Remote Similarity NPC210094
0.6122 Remote Similarity NPC253685
0.6067 Remote Similarity NPC115760
0.5876 Remote Similarity NPC229409
0.5843 Remote Similarity NPC101191
0.5833 Remote Similarity NPC46202
0.5833 Remote Similarity NPC64051
0.5758 Remote Similarity NPC195257
0.5714 Remote Similarity NPC610187
0.5682 Remote Similarity NPC19709
0.5618 Remote Similarity NPC189142
0.5618 Remote Similarity NPC77660
0.5568 Remote Similarity NPC331652
0.5543 Remote Similarity NPC22832
0.5543 Remote Similarity NPC243930
0.5506 Remote Similarity NPC39360
0.5506 Remote Similarity NPC29763
0.5506 Remote Similarity NPC210003
0.5495 Remote Similarity NPC27942
0.5484 Remote Similarity NPC602805
0.5444 Remote Similarity NPC95090
0.5444 Remote Similarity NPC27408
0.5385 Remote Similarity NPC48479
0.5385 Remote Similarity NPC181712
0.5319 Remote Similarity NPC607707
0.5316 Remote Similarity NPC108406
0.5269 Remote Similarity NPC235260
0.5269 Remote Similarity NPC49344
0.5269 Remote Similarity NPC155763
0.5263 Remote Similarity NPC190003
0.5263 Remote Similarity NPC601586
0.5222 Remote Similarity NPC473043
0.5213 Remote Similarity NPC601710
0.5208 Remote Similarity NPC4390
0.519 Remote Similarity NPC234133
0.5155 Remote Similarity NPC606546
0.5146 Remote Similarity NPC479765
0.514 Remote Similarity NPC472993
0.5122 Remote Similarity NPC183950
0.5122 Remote Similarity NPC47781
0.5089 Remote Similarity NPC471030
0.5053 Remote Similarity NPC264735
0.5049 Remote Similarity NPC479766

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC549306 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
0.6322 Remote Similarity NPD4338 Clinical (unspecified phase)

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