Natural Product: NPC46591

Natural Product IDNPC46591
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2S,3R,4R)-2-(5-Methoxy-3,4-Methylenedioxyphenyl)-4-(5-Methoxy-3,4-Methylenedioxybenzyl)-3-Furanmethanol
IUPAC Name [(2S,3R,4R)-2-(7-methoxy-1,3-benzodioxol-5-yl)-4-[(7-methoxy-1,3-benzodioxol-5-yl)methyl]oxolan-3-yl]methanol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL222581
PubChem CID 16215161
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003422] 7,9'-epoxylignans

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 NEKCZSOZRUNPLY-AUSJPIAWSA-N
Standard InCHI InChI=1S/C22H24O8/c1-24-16-4-12(5-18-21(16)29-10-27-18)3-14-9-26-20(15(14)8-23)13-6-17(25-2)22-19(7-13)28-11-30-22/h4-7,14-15,20,23H,3,8-11H2,1-2H3/t14-,15-,20+/m0/s1
SMILES COc1cc(C[C@H]2CO[C@H](c3cc(c4c(c3)OCO4)OC)[C@H]2CO)cc2c1OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   416.15 Volume:   400.789
?
Van der Waals volume.
Dense:   1.038 LogP:   2.145
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.405
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.638
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   25.0
TPSA:   84.84
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.77 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.806 Fsp3:   0.455
MCE-18:   87.75
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.35 Fluc inhibitor:   0.344
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.047
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.238
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.101 Promiscuous compounds:   0.305

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.923 MDCK Permeability:   -4.857
Pgp-inhibitor:   0.33 Pgp-substrate:   0.018
PAMPA:   0.115
?
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):   0.0
20% Bioavailability (F20%):   0.02 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.211

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.889 MRP1:   0.792
Plasma Protein Binding (PPB):   91.215% Volume Distribution (VD):   0.381
Fu: 6.703%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.982
OATP1B3 inhibitor:   0.922 BCRP inhibitor:   0.017
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.942 CYP1A2-substrate:   0.18
CYP2C19-inhibitor:   0.989 CYP2C19-substrate:   0.035
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.999
CYP2D6-inhibitor:   0.976 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.053 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.008
HLM stability:   0.271
?
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):  4.391 Half-life (T1/2):  0.97

ADMET: Toxicity

hERG Blockers:  0.173 hERG Blockers (10um):  0.353
Human Hepatotoxicity (H-HT):  0.91 Drug-induced Liver Injury (DILI):  0.942
AMES Toxicity:  0.717 Rat Oral Acute Toxicity:  0.284
Maximum Recommended Daily Dose:  0.454 Skin Sensitization:  0.905
Carcinogencity:  0.86 Eye Corrosion:  0.001
Eye Irritation:  0.875 Respiratory Toxicity:  0.123
Drug-induced Neurotoxicity:  0.679 Ototoxicity:  0.644
Hematotoxicity:  0.642 Drug-induced Nephrotoxicity:  0.701
Genotoxicity:  0.934 RPMI-8226 Immunitoxicity:  0.197
A549 Cytotoxicity:  0.19 Hek293 Cytotoxicity:  0.376
BCF:   1.62
?
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:   3.88
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.937
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.684
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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
NPO17040 Peperomia duclouxii Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[16499322]
NPO17040 Peperomia duclouxii Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[17358082]
NPO17040 Peperomia duclouxii Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[17547458]
NPO17040 Peperomia duclouxii Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17040 Peperomia duclouxii Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17040 Peperomia duclouxii Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17040 Peperomia duclouxii Species Piperaceae 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
NPT1374 Cell line WI-38 Homo sapiens IC50 = 74.3 ug.mL-1 PMID[26110519]
NPT1475 Cell line WI-38 VA13 Homo sapiens IC50 = 99.1 ug.mL-1 PMID[12444692]
NPT65 Cell line HepG2 Homo sapiens IC50 = 72.0 ug.mL-1 PMID[26211462]

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 NPC46591 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
0.6964 Remote Similarity NPC47181
0.6429 Remote Similarity NPC206882
0.62 Remote Similarity NPC150534
0.5962 Remote Similarity NPC148893
0.5962 Remote Similarity NPC25333
0.5962 Remote Similarity NPC49235
0.5926 Remote Similarity NPC11453
0.5789 Remote Similarity NPC283949
0.5574 Remote Similarity NPC166884
0.5574 Remote Similarity NPC141569
0.5574 Remote Similarity NPC477701
0.5517 Remote Similarity NPC185071
0.5484 Remote Similarity NPC287124
0.541 Remote Similarity NPC226547
0.5397 Remote Similarity NPC486558
0.5397 Remote Similarity NPC282833
0.5385 Remote Similarity NPC64201
0.5345 Remote Similarity NPC92693
0.5342 Remote Similarity NPC605526
0.5323 Remote Similarity NPC187998
0.5323 Remote Similarity NPC257582
0.5323 Remote Similarity NPC241522
0.5254 Remote Similarity NPC40237
0.5172 Remote Similarity NPC192255
0.5094 Remote Similarity NPC31530
0.5079 Remote Similarity NPC12728

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC46591 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