Natural Product: NPC546067

Natural Product IDNPC546067
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Isoflavone glycoside
IUPAC Name 6,7-dihydroxy-3-[4-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxyphenyl]chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 ZWSNUPOSLDAWJS-QNDFHXLGSA-N
Standard InCHI InChI=1S/C21H20O10/c22-7-16-18(26)19(27)20(28)21(31-16)30-10-3-1-9(2-4-10)12-8-29-15-6-14(24)13(23)5-11(15)17(12)25/h1-6,8,16,18-24,26-28H,7H2/t16-,18-,19+,20-,21-/m1/s1
SMILES O=C1C(C2=CC=C(O[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)C=C2)=COC2=CC(O)=C(O)C=C12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   432.11 Volume:   404.357
?
Van der Waals volume.
Dense:   1.069 LogP:   0.347
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.184
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.324
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   24.0
TPSA:   170.05
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.31 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.77 Fsp3:   0.286
MCE-18:   84.259
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.638 Fluc inhibitor:   0.328
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.986
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.736
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.327 Promiscuous compounds:   0.518

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.381 MDCK Permeability:   -5.167
Pgp-inhibitor:   0.0 Pgp-substrate:   0.043
PAMPA:   0.999
?
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):   0.865
20% Bioavailability (F20%):   0.57 30% Bioavailability (F30%):   0.987
50% Bioavailability (F50%):   0.984

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.145
Plasma Protein Binding (PPB):   77.081% Volume Distribution (VD):   -0.299
Fu: 22.544%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.12
BSEP inhibitor:   0.005

ADMET: Metabolism

CYP1A2-inhibitor:   0.104 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.213
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.0
?
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):  3.537 Half-life (T1/2):  3.629

ADMET: Toxicity

hERG Blockers:  0.062 hERG Blockers (10um):  0.227
Human Hepatotoxicity (H-HT):  0.715 Drug-induced Liver Injury (DILI):  0.985
AMES Toxicity:  0.942 Rat Oral Acute Toxicity:  0.073
Maximum Recommended Daily Dose:  0.116 Skin Sensitization:  0.994
Carcinogencity:  0.376 Eye Corrosion:  0.0
Eye Irritation:  0.47 Respiratory Toxicity:  0.034
Drug-induced Neurotoxicity:  0.005 Ototoxicity:  0.964
Hematotoxicity:  0.172 Drug-induced Nephrotoxicity:  0.498
Genotoxicity:  0.939 RPMI-8226 Immunitoxicity:  0.046
A549 Cytotoxicity:  0.754 Hek293 Cytotoxicity:  0.266
BCF:   0.762
?
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:   3.446
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.954
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.348
?
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
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11746-997-0093-1]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. Wrocław, Poland 2004–2005 DOI[10.1016/J.FOODCHEM.2006.08.014]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. retail stores, supermarkets and market stalls in Forssa and in the Helsinki area 2003–2005 DOI[10.1016/j.jfca.2006.05.007]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0021-9258(18)90865-3]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0168-9452(02)00136-X]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0168-9452(02)00136-X]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1021/jf950732o]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1023/A:1024390522259]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[10775096]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. root n.a. PMID[1622242]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[16659156]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[16668466]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[18460139]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[20963508]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[22537213]
NPO7635 Glycine max Species Fabaceae Eukaryota Seeds Tekirdag, Turkey PMID[24499198]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[25053043]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[25070365]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. seed n.a. PMID[25369450]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[25369450]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO7635 Glycine max Species Fabaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO7635 Glycine max Species Fabaceae Eukaryota Testa n.a. n.a. Database[FooDB]
NPO7635 Glycine max Species Fabaceae Eukaryota Stem n.a. n.a. Database[FooDB]
NPO7635 Glycine max Species Fabaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO7635 Glycine max Species Fabaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO7635 Glycine max Species Fabaceae Eukaryota Sprout Seedling n.a. n.a. Database[FooDB]
NPO7635 Glycine max Species Fabaceae Eukaryota Pericarp n.a. n.a. Database[FooDB]
NPO7635 Glycine max Species Fabaceae Eukaryota Oil n.a. n.a. Database[FooDB]
NPO7635 Glycine max Species Fabaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO7635 Glycine max Species Fabaceae Eukaryota Hypocotyl n.a. n.a. Database[FooDB]
NPO7635 Glycine max Species Fabaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO7635 Glycine max Species Fabaceae Eukaryota Cotyledon n.a. n.a. Database[FooDB]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. seed n.a. Database[MetaboLights]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. Database[MetaboLights]
NPO7635 Glycine max Species Fabaceae Eukaryota Seeds n.a. Database[Phenol-Explorer]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7635 Glycine max Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7635 Glycine max 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

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 NPC546067 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
0.7917 Intermediate Similarity NPC258035
0.72 Intermediate Similarity NPC156457
0.6933 Remote Similarity NPC45165
0.6933 Remote Similarity NPC135345
0.6883 Remote Similarity NPC73511
0.6753 Remote Similarity NPC161749
0.6538 Remote Similarity NPC603782
0.642 Remote Similarity NPC229729
0.6418 Remote Similarity NPC10467
0.6329 Remote Similarity NPC105511
0.6173 Remote Similarity NPC138540
0.6125 Remote Similarity NPC197896
0.6125 Remote Similarity NPC313163
0.6125 Remote Similarity NPC234739
0.6104 Remote Similarity NPC25547
0.6098 Remote Similarity NPC479401
0.6024 Remote Similarity NPC601607
0.5976 Remote Similarity NPC100720
0.5976 Remote Similarity NPC205076
0.5952 Remote Similarity NPC307518
0.5904 Remote Similarity NPC479402
0.5875 Remote Similarity NPC160515
0.561 Remote Similarity NPC211014
0.5581 Remote Similarity NPC607201
0.5529 Remote Similarity NPC481043
0.5529 Remote Similarity NPC224462
0.5529 Remote Similarity NPC80140
0.5517 Remote Similarity NPC48773
0.5517 Remote Similarity NPC479407
0.5422 Remote Similarity NPC143851
0.5402 Remote Similarity NPC479406
0.5333 Remote Similarity NPC603384
0.5238 Remote Similarity NPC259070
0.5238 Remote Similarity NPC58053
0.5222 Remote Similarity NPC487212
0.5217 Remote Similarity NPC479405
0.5217 Remote Similarity NPC218490
0.5176 Remote Similarity NPC64305
0.5161 Remote Similarity NPC479404
0.5116 Remote Similarity NPC186807
0.5059 Remote Similarity NPC289667
0.5059 Remote Similarity NPC348541

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC546067 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
0.6753 Remote Similarity NPD4381 Clinical (unspecified phase)
0.5301 Remote Similarity NPD3818 Discontinued

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