Natural Product: NPC165128

Natural Product IDNPC165128
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (7R,8S,8'r)-7-Ethoxy-3,4:3',4'-Dimethylenedioxy-8,8'-Lignan
IUPAC Name 5-[(1R,2S,3R)-4-(1,3-benzodioxol-5-yl)-1-ethoxy-2,3-dimethylbutyl]-1,3-benzodioxole
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL259667
PubChem CID 24939236
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0001969] Dibenzylbutane lignans

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 QBTFMURMTWNANN-ZCCHDVMBSA-N
Standard InCHI InChI=1S/C22H26O5/c1-4-23-22(17-6-8-19-21(11-17)27-13-25-19)15(3)14(2)9-16-5-7-18-20(10-16)26-12-24-18/h5-8,10-11,14-15,22H,4,9,12-13H2,1-3H3/t14-,15+,22-/m1/s1
SMILES CCO[C@H]([C@H]([C@@H](Cc1ccc2c(c1)OCO2)C)C)c1ccc2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   370.18 Volume:   382.975
?
Van der Waals volume.
Dense:   0.967 LogP:   4.52
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.015
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.295
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   20.0
TPSA:   46.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.705 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.481 Fsp3:   0.455
MCE-18:   65.625
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.447 Fluc inhibitor:   0.574
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.022
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.06
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.329 Promiscuous compounds:   0.117

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.758 MDCK Permeability:   -4.562
Pgp-inhibitor:   0.359 Pgp-substrate:   0.002
PAMPA:   0.092
?
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%):   0.003 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.382

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.96 MRP1:   0.432
Plasma Protein Binding (PPB):   98.052% Volume Distribution (VD):   0.214
Fu: 2.398%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.588
OATP1B3 inhibitor:   0.546 BCRP inhibitor:   0.004
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.812 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.838 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.887 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.003 CYP2C8-inhibitor:   0.518
HLM stability:   0.896
?
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):  3.465 Half-life (T1/2):  0.656

ADMET: Toxicity

hERG Blockers:  0.338 hERG Blockers (10um):  0.762
Human Hepatotoxicity (H-HT):  0.452 Drug-induced Liver Injury (DILI):  0.839
AMES Toxicity:  0.59 Rat Oral Acute Toxicity:  0.271
Maximum Recommended Daily Dose:  0.163 Skin Sensitization:  0.099
Carcinogencity:  0.822 Eye Corrosion:  0.074
Eye Irritation:  0.878 Respiratory Toxicity:  0.272
Drug-induced Neurotoxicity:  0.367 Ototoxicity:  0.515
Hematotoxicity:  0.442 Drug-induced Nephrotoxicity:  0.599
Genotoxicity:  0.453 RPMI-8226 Immunitoxicity:  0.074
A549 Cytotoxicity:  0.175 Hek293 Cytotoxicity:  0.422
BCF:   2.361
?
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:   4.409
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.374
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.598
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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
NPO2754 Iryanthera lancifolia Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[10579855]
NPO2754 Iryanthera lancifolia Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[18242997]
NPO2754 Iryanthera lancifolia Species Myristicaceae 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
NPT83 Cell line MCF7 Homo sapiens MED = 10.0 uM PMID[18242997]
NPT83 Cell line MCF7 Homo sapiens Ratio = 6.9 n.a. PMID[23305465]
NPT83 Cell line MCF7 Homo sapiens Activity = 0.01 % PMID[17960925]
NPT83 Cell line MCF7 Homo sapiens Activity = 84.0 % DrugMatrix in vivo data: Pathology

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 NPC165128 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
0.6444 Remote Similarity NPC80241
0.6444 Remote Similarity NPC301641
0.6444 Remote Similarity NPC485483
0.6271 Remote Similarity NPC471505
0.614 Remote Similarity NPC47181
0.6042 Remote Similarity NPC271208
0.6042 Remote Similarity NPC233224
0.6042 Remote Similarity NPC610263
0.6 Remote Similarity NPC480478
0.5918 Remote Similarity NPC344161
0.5882 Remote Similarity NPC476748
0.58 Remote Similarity NPC171928
0.58 Remote Similarity NPC158526
0.58 Remote Similarity NPC129687
0.58 Remote Similarity NPC33611
0.58 Remote Similarity NPC16830
0.58 Remote Similarity NPC100223
0.58 Remote Similarity NPC600801
0.5577 Remote Similarity NPC57119
0.5577 Remote Similarity NPC158471
0.5577 Remote Similarity NPC226862
0.5536 Remote Similarity NPC143895
0.5455 Remote Similarity NPC189474
0.5455 Remote Similarity NPC192255
0.537 Remote Similarity NPC249788
0.537 Remote Similarity NPC485482
0.537 Remote Similarity NPC227160
0.537 Remote Similarity NPC82111
0.5273 Remote Similarity NPC487685
0.5179 Remote Similarity NPC104077
0.5179 Remote Similarity NPC219671
0.5179 Remote Similarity NPC147616
0.5179 Remote Similarity NPC485480
0.5098 Remote Similarity NPC40352
0.5098 Remote Similarity NPC213711

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC165128 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