Natural Product: NPC181079

Natural Product IDNPC181079
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (8R,8'r,9S)-4,4',9-Trihydroxy-3,3'-Dimethoxy-9,9'-Epoxylignan
IUPAC Name (2S,3R,4R)-3,4-bis[(4-hydroxy-3-methoxyphenyl)methyl]oxolan-2-ol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL584197
PubChem CID 45481967
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003424] 9,9'-epoxylignans
            • [CHEMONTID:0001968] Dibenzylbutyrolactols

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 AQTZWMJGAOIWFV-MDOVXXIYSA-N
Standard InCHI InChI=1S/C20H24O6/c1-24-18-9-12(3-5-16(18)21)7-14-11-26-20(23)15(14)8-13-4-6-17(22)19(10-13)25-2/h3-6,9-10,14-15,20-23H,7-8,11H2,1-2H3/t14-,15+,20-/m0/s1
SMILES COc1cc(ccc1O)C[C@H]1CO[C@@H]([C@@H]1Cc1ccc(c(c1)OC)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   360.16 Volume:   365.729
?
Van der Waals volume.
Dense:   0.985 LogP:   1.765
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.875
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.85
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   17.0
TPSA:   88.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.733 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.448 Fsp3:   0.4
MCE-18:   59.143
?
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:   0.345 Fluc inhibitor:   0.041
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.028
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.176
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.129 Promiscuous compounds:   0.219

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.059 MDCK Permeability:   -4.751
Pgp-inhibitor:   0.33 Pgp-substrate:   0.688
PAMPA:   0.023
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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):   0.017
20% Bioavailability (F20%):   0.851 30% Bioavailability (F30%):   0.823
50% Bioavailability (F50%):   0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.01 MRP1:   0.9
Plasma Protein Binding (PPB):   88.891% Volume Distribution (VD):   -0.1
Fu: 13.592%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.992 BCRP inhibitor:   0.544
BSEP inhibitor:   0.858

ADMET: Metabolism

CYP1A2-inhibitor:   0.627 CYP1A2-substrate:   0.825
CYP2C19-inhibitor:   0.998 CYP2C19-substrate:   0.724
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.163
CYP2D6-inhibitor:   0.938 CYP2D6-substrate:   0.905
CYP3A4-inhibitor:   0.013 CYP3A4-substrate:   0.055
CYP2B6-substrate:   0.008 CYP2C8-inhibitor:   1.0
HLM stability:   0.931
?
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):  9.024 Half-life (T1/2):  1.706

ADMET: Toxicity

hERG Blockers:  0.091 hERG Blockers (10um):  0.549
Human Hepatotoxicity (H-HT):  0.762 Drug-induced Liver Injury (DILI):  0.734
AMES Toxicity:  0.936 Rat Oral Acute Toxicity:  0.4
Maximum Recommended Daily Dose:  0.58 Skin Sensitization:  0.992
Carcinogencity:  0.496 Eye Corrosion:  0.032
Eye Irritation:  0.986 Respiratory Toxicity:  0.597
Drug-induced Neurotoxicity:  0.805 Ototoxicity:  0.434
Hematotoxicity:  0.482 Drug-induced Nephrotoxicity:  0.804
Genotoxicity:  0.86 RPMI-8226 Immunitoxicity:  0.25
A549 Cytotoxicity:  0.893 Hek293 Cytotoxicity:  0.71
BCF:   1.122
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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:   3.657
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.825
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.232
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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
NPO12339 Daphne feddei Species Thymelaeaceae Eukaryota stem bark Kunming, Yunnan Province, China n.a. PMID[18986199]
NPO23754 Solanum aculeatissimum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12339 Daphne feddei Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21329 Ilyonectria destructans Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10211 Pajanelia multijuga n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO23754 Solanum aculeatissimum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21329 Ilyonectria destructans Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23754 Solanum aculeatissimum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10211 Pajanelia multijuga n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO12339 Daphne feddei Species Thymelaeaceae 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
NPT113 Cell line RAW264.7 Mus musculus IC50 = 4000.0 nM PMID[18986199]

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 NPC181079 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 NPC173308
0.7963 Intermediate Similarity NPC169973
0.6809 Remote Similarity NPC31344
0.6809 Remote Similarity NPC317769
0.66 Remote Similarity NPC482890
0.6327 Remote Similarity NPC236522
0.5926 Remote Similarity NPC68779
0.5926 Remote Similarity NPC108598
0.5926 Remote Similarity NPC487680
0.5893 Remote Similarity NPC253481
0.5893 Remote Similarity NPC253722
0.5893 Remote Similarity NPC475875
0.5833 Remote Similarity NPC85488
0.5745 Remote Similarity NPC165133
0.5745 Remote Similarity NPC242885
0.5745 Remote Similarity NPC95614
0.5745 Remote Similarity NPC232316
0.5741 Remote Similarity NPC171550
0.5741 Remote Similarity NPC134764
0.5714 Remote Similarity NPC275950
0.569 Remote Similarity NPC187998
0.569 Remote Similarity NPC185908
0.569 Remote Similarity NPC257582
0.569 Remote Similarity NPC241522
0.569 Remote Similarity NPC482891
0.5636 Remote Similarity NPC283949
0.5593 Remote Similarity NPC23646
0.5593 Remote Similarity NPC485397
0.5517 Remote Similarity NPC273657
0.55 Remote Similarity NPC486558
0.541 Remote Similarity NPC610284
0.5385 Remote Similarity NPC487676
0.5333 Remote Similarity NPC110699
0.5333 Remote Similarity NPC106920
0.5333 Remote Similarity NPC300776
0.5333 Remote Similarity NPC15811
0.5333 Remote Similarity NPC176814
0.5333 Remote Similarity NPC4982
0.5333 Remote Similarity NPC106055
0.5333 Remote Similarity NPC606629
0.5323 Remote Similarity NPC31751
0.5323 Remote Similarity NPC42300
0.5254 Remote Similarity NPC226547
0.5246 Remote Similarity NPC476345
0.5246 Remote Similarity NPC606339
0.5238 Remote Similarity NPC278961
0.5238 Remote Similarity NPC487679
0.5238 Remote Similarity NPC64201
0.5238 Remote Similarity NPC113680
0.5238 Remote Similarity NPC487678
0.5217 Remote Similarity NPC156840
0.5208 Remote Similarity NPC221049
0.5208 Remote Similarity NPC140359
0.5161 Remote Similarity NPC485282
0.5161 Remote Similarity NPC67247
0.5161 Remote Similarity NPC485283
0.5161 Remote Similarity NPC485281
0.5156 Remote Similarity NPC282291
0.5156 Remote Similarity NPC166137
0.5156 Remote Similarity NPC608199
0.5102 Remote Similarity NPC471693
0.5094 Remote Similarity NPC56214
0.5091 Remote Similarity NPC5428
0.5091 Remote Similarity NPC607444
0.5077 Remote Similarity NPC120852
0.5077 Remote Similarity NPC216223

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC181079 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