Natural Product: NPC213074

Natural Product IDNPC213074
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (7S,8S)-Dihydrodehydrodiconiferyl Alcohol 9-O-Beta-D-Glucopyranoside
IUPAC Name (2R,3R,4S,5S,6R)-2-[[(2S,3S)-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-7-methoxy-2,3-dihydro-1-benzofuran-3-yl]methoxy]-6-(hydroxymethyl)oxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3098860
PubChem CID 72945100
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003405] 2-arylbenzofuran flavonoids

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 VTKHRLZMWODHJA-GLLXQACZSA-N
Standard InCHI InChI=1S/C26H34O11/c1-33-18-10-14(5-6-17(18)29)24-16(12-35-26-23(32)22(31)21(30)20(11-28)36-26)15-8-13(4-3-7-27)9-19(34-2)25(15)37-24/h5-6,8-10,16,20-24,26-32H,3-4,7,11-12H2,1-2H3/t16-,20-,21-,22+,23-,24-,26-/m1/s1
SMILES COc1cc(ccc1O)[C@@H]1[C@H](CO[C@H]2[C@@H]([C@H]([C@@H]([C@@H](CO)O2)O)O)O)c2cc(CCCO)cc(c2O1)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   522.21 Volume:   504.9
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Van der Waals volume.
Dense:   1.034 LogP:   1.36
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.775
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.262
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The logarithm of aqueous solubility value.
Rotatable Bonds:   10.0 Rigid Bonds:   22.0
TPSA:   167.53
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Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.255 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.331 Fsp3:   0.538
MCE-18:   87.1
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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:   Accepted BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.505 Fluc inhibitor:   0.141
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.027
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.645
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.052 Promiscuous compounds:   0.069

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.799 MDCK Permeability:   -5.133
Pgp-inhibitor:   0.015 Pgp-substrate:   0.651
PAMPA:   0.484
?
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):   0.213
20% Bioavailability (F20%):   0.171 30% Bioavailability (F30%):   0.898
50% Bioavailability (F50%):   0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.007 MRP1:   0.263
Plasma Protein Binding (PPB):   69.003% Volume Distribution (VD):   -0.404
Fu: 29.674%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.371
BSEP inhibitor:   0.452

ADMET: Metabolism

CYP1A2-inhibitor:   0.779 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.974 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.969 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.024 CYP2D6-substrate:   0.086
CYP3A4-inhibitor:   0.259 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.988
HLM stability:   0.001
?
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):  3.002 Half-life (T1/2):  2.66

ADMET: Toxicity

hERG Blockers:  0.057 hERG Blockers (10um):  0.154
Human Hepatotoxicity (H-HT):  0.763 Drug-induced Liver Injury (DILI):  0.316
AMES Toxicity:  0.661 Rat Oral Acute Toxicity:  0.017
Maximum Recommended Daily Dose:  0.021 Skin Sensitization:  0.988
Carcinogencity:  0.131 Eye Corrosion:  0.0
Eye Irritation:  0.387 Respiratory Toxicity:  0.027
Drug-induced Neurotoxicity:  0.031 Ototoxicity:  0.976
Hematotoxicity:  0.315 Drug-induced Nephrotoxicity:  0.805
Genotoxicity:  0.031 RPMI-8226 Immunitoxicity:  0.08
A549 Cytotoxicity:  0.35 Hek293 Cytotoxicity:  0.29
BCF:   0.586
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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:   3.127
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.0
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.887
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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
NPO31082 Pulsatilla koreana Species Ranunculaceae Eukaryota n.a. root n.a. PMID[15473660]
NPO31082 Pulsatilla koreana Species Ranunculaceae Eukaryota Roots n.a. n.a. PMID[15730260]
NPO31082 Pulsatilla koreana Species Ranunculaceae Eukaryota Roots n.a. n.a. PMID[24360605]
NPO31082 Pulsatilla koreana Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT2 Others Unspecified n.a. IC50 = 82800.0 nM PMID[21907579]

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 NPC213074 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
1.0 High Similarity NPC114505
0.8816 High Similarity NPC15956
0.8072 Intermediate Similarity NPC479449
0.8052 Intermediate Similarity NPC193473
0.8052 Intermediate Similarity NPC600128
0.7791 Intermediate Similarity NPC98624
0.75 Intermediate Similarity NPC472710
0.75 Intermediate Similarity NPC472709
0.7439 Intermediate Similarity NPC224674
0.7439 Intermediate Similarity NPC64475
0.6053 Remote Similarity NPC29799
0.6053 Remote Similarity NPC263367
0.6053 Remote Similarity NPC54743
0.6047 Remote Similarity NPC478701
0.5747 Remote Similarity NPC217635
0.5581 Remote Similarity NPC199539
0.55 Remote Similarity NPC316539
0.5435 Remote Similarity NPC302610
0.5385 Remote Similarity NPC115203
0.5309 Remote Similarity NPC278961
0.5309 Remote Similarity NPC113680
0.5055 Remote Similarity NPC79429
0.5053 Remote Similarity NPC125495

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC213074 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
NPD

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