Natural Product: NPC131971

Natural Product IDNPC131971
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Dimericconiferylacetate
IUPAC Name [(E)-3-[(2S,3R)-3-(acetyloxymethyl)-2-(4-hydroxy-3-methoxyphenyl)-7-methoxy-2,3-dihydro-1-benzofuran-5-yl]prop-2-enyl] acetate
Synonyms Dimericconiferylacetate
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL514122
PubChem CID 44584272
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 TYXVTGSQLKCKCF-FDTLDTTQSA-N
Standard InCHI InChI=1S/C24H26O8/c1-14(25)30-9-5-6-16-10-18-19(13-31-15(2)26)23(32-24(18)22(11-16)29-4)17-7-8-20(27)21(12-17)28-3/h5-8,10-12,19,23,27H,9,13H2,1-4H3/b6-5+/t19-,23+/m0/s1
SMILES COc1cc(/C=C/COC(=O)C)cc2c1O[C@@H]([C@H]2COC(=O)C)c1ccc(c(c1)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   442.16 Volume:   444.584
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Van der Waals volume.
Dense:   0.995 LogP:   3.162
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.002
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.384
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The logarithm of aqueous solubility value.
Rotatable Bonds:   10.0 Rigid Bonds:   19.0
TPSA:   100.52
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Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.617 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.536 Fsp3:   0.333
MCE-18:   62.5
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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:   0
Colloidal aggregators:   0.651 Fluc inhibitor:   0.682
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.102
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.747
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.247 Promiscuous compounds:   0.182

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.118 MDCK Permeability:   -4.687
Pgp-inhibitor:   0.969 Pgp-substrate:   0.131
PAMPA:   0.006
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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):   0.002
20% Bioavailability (F20%):   0.578 30% Bioavailability (F30%):   0.822
50% Bioavailability (F50%):   0.965

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.018 MRP1:   0.889
Plasma Protein Binding (PPB):   87.933% Volume Distribution (VD):   -0.207
Fu: 12.906%
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The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.917
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.047 CYP1A2-substrate:   0.022
CYP2C19-inhibitor:   0.02 CYP2C19-substrate:   0.037
CYP2C9-inhibitor:   0.03 CYP2C9-substrate:   0.283
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.595
CYP3A4-inhibitor:   0.671 CYP3A4-substrate:   0.063
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.961
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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):  3.661 Half-life (T1/2):  0.978

ADMET: Toxicity

hERG Blockers:  0.075 hERG Blockers (10um):  0.363
Human Hepatotoxicity (H-HT):  0.526 Drug-induced Liver Injury (DILI):  0.689
AMES Toxicity:  0.843 Rat Oral Acute Toxicity:  0.187
Maximum Recommended Daily Dose:  0.541 Skin Sensitization:  0.842
Carcinogencity:  0.759 Eye Corrosion:  0.002
Eye Irritation:  0.782 Respiratory Toxicity:  0.104
Drug-induced Neurotoxicity:  0.276 Ototoxicity:  0.295
Hematotoxicity:  0.516 Drug-induced Nephrotoxicity:  0.516
Genotoxicity:  0.799 RPMI-8226 Immunitoxicity:  0.136
A549 Cytotoxicity:  0.162 Hek293 Cytotoxicity:  0.311
BCF:   0.833
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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:   3.621
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.217
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.676
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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
NPO30782 Brazilian propolis n.a. n.a. n.a. n.a. n.a. n.a. DOI[10.1248/cpb.47.1521]
NPO30782 Brazilian propolis n.a. n.a. n.a. n.a. n.a. n.a. PMID[11000036]
NPO30782 Brazilian propolis n.a. n.a. n.a. n.a. n.a. n.a. PMID[8951168]
NPO30782 Brazilian propolis n.a. n.a. n.a. n.a. Brazilian propolis n.a. PMID[9677271]
NPO30782 Brazilian propolis n.a. n.a. n.a. 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
NPT453 Cell line HT-1080 Homo sapiens ED50 = 38.92 ug ml-1 PMID[12350153]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. ED50 = 39.86 ug ml-1 PMID[9677271]

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 NPC131971 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 NPC15189
0.8413 Intermediate Similarity NPC480707
0.8358 Intermediate Similarity NPC480698
0.7324 Intermediate Similarity NPC236166
0.7183 Intermediate Similarity NPC216916
0.7183 Intermediate Similarity NPC45943
0.6486 Remote Similarity NPC469889
0.6406 Remote Similarity NPC187616
0.6406 Remote Similarity NPC193026
0.6406 Remote Similarity NPC49603
0.6389 Remote Similarity NPC480704
0.6351 Remote Similarity NPC180768
0.6282 Remote Similarity NPC115203
0.6143 Remote Similarity NPC206413
0.6143 Remote Similarity NPC482649
0.6143 Remote Similarity NPC149003
0.6143 Remote Similarity NPC482647
0.6143 Remote Similarity NPC482648
0.6143 Remote Similarity NPC482651
0.6143 Remote Similarity NPC194244
0.6143 Remote Similarity NPC482650
0.5915 Remote Similarity NPC253878
0.5915 Remote Similarity NPC471414
0.5857 Remote Similarity NPC284881
0.5857 Remote Similarity NPC93433
0.5857 Remote Similarity NPC474444
0.5854 Remote Similarity NPC125495
0.5797 Remote Similarity NPC156502
0.5797 Remote Similarity NPC10737
0.5732 Remote Similarity NPC302610
0.5333 Remote Similarity NPC163898
0.5316 Remote Similarity NPC480633
0.5309 Remote Similarity NPC480705
0.5147 Remote Similarity NPC154258
0.5135 Remote Similarity NPC209985
0.506 Remote Similarity NPC478701
0.5053 Remote Similarity NPC228357

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC131971 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