Natural Product: NPC111247

Natural Product IDNPC111247
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7R,8R-4,9,9'-Trihydroxy-3,3'-Dimethoxy-8-O-4'-Neolignan
IUPAC Name (1R,2R)-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]propane-1,3-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1760591
PubChem CID 13893598
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds

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 DBIKJXXBCAHHMC-WOJBJXKFSA-N
Standard InCHI InChI=1S/C20H26O7/c1-25-17-11-14(6-7-15(17)23)20(24)19(12-22)27-16-8-5-13(4-3-9-21)10-18(16)26-2/h5-8,10-11,19-24H,3-4,9,12H2,1-2H3/t19-,20-/m1/s1
SMILES COc1cc(ccc1O)[C@H]([C@@H](CO)Oc1ccc(CCCO)cc1OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   378.17 Volume:   383.076
?
Van der Waals volume.
Dense:   0.987 LogP:   0.945
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.226
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.585
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   10.0 Rigid Bonds:   12.0
TPSA:   108.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.499 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.071 Fsp3:   0.4
MCE-18:   28.0
?
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:   0.527 Fluc inhibitor:   0.218
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.008
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.232
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.105 Promiscuous compounds:   0.286

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.034 MDCK Permeability:   -4.763
Pgp-inhibitor:   0.065 Pgp-substrate:   0.218
PAMPA:   0.693
?
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):   0.004
20% Bioavailability (F20%):   0.035 30% Bioavailability (F30%):   0.151
50% Bioavailability (F50%):   0.846

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.376
Plasma Protein Binding (PPB):   72.253% Volume Distribution (VD):   0.025
Fu: 27.421%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.102
BSEP inhibitor:   0.882

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.956 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.897 CYP2C9-substrate:   0.061
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.023
CYP3A4-inhibitor:   0.026 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.967
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):  6.948 Half-life (T1/2):  1.73

ADMET: Toxicity

hERG Blockers:  0.115 hERG Blockers (10um):  0.506
Human Hepatotoxicity (H-HT):  0.667 Drug-induced Liver Injury (DILI):  0.065
AMES Toxicity:  0.248 Rat Oral Acute Toxicity:  0.042
Maximum Recommended Daily Dose:  0.076 Skin Sensitization:  0.489
Carcinogencity:  0.159 Eye Corrosion:  0.003
Eye Irritation:  0.713 Respiratory Toxicity:  0.118
Drug-induced Neurotoxicity:  0.182 Ototoxicity:  0.893
Hematotoxicity:  0.161 Drug-induced Nephrotoxicity:  0.76
Genotoxicity:  0.011 RPMI-8226 Immunitoxicity:  0.052
A549 Cytotoxicity:  0.144 Hek293 Cytotoxicity:  0.188
BCF:   0.279
?
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:   2.742
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.106
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.272
?
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
NPO4001 Berberis koreana Species Berberidaceae Eukaryota n.a. n.a. n.a. PMID[19813743]
NPO4001 Berberis koreana Species Berberidaceae Eukaryota trunk Jeju island, Korea 2005-Dec PMID[21420296]
NPO4001 Berberis koreana Species Berberidaceae Eukaryota n.a. n.a. n.a. PMID[21420296]
NPO29118 Euonymus alatus Species Celastraceae Eukaryota leaves and twigs n.a. n.a. PMID[21435874]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. rhizome n.a. PMID[21936523]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota Rhizomes n.a. n.a. PMID[21936523]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota rhizomes n.a. n.a. PMID[22951040]
NPO29118 Euonymus alatus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29118 Euonymus alatus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29118 Euonymus alatus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29118 Euonymus alatus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29118 Euonymus alatus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO5681 Acorus gramineus Species Acoraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29118 Euonymus alatus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4001 Berberis koreana Species Berberidaceae 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
NPT34 Cell line BV-2 Mus musculus IC50 = 58490.0 nM PMID[21420296]
NPT81 Cell line A549 Homo sapiens IC50 > 30000.0 nM PMID[21420296]
NPT147 Cell line SK-MEL-2 Homo sapiens IC50 > 30000.0 nM PMID[21420296]
NPT574 Cell line XF498 Homo sapiens IC50 = 26560.0 nM PMID[21420296]
NPT146 Cell line SK-OV-3 Homo sapiens IC50 > 30000.0 nM PMID[21420296]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 63400.0 nM PMID[21435874]
NPT81 Cell line A549 Homo sapiens IC50 > 10000.0 nM PMID[21936523]
NPT146 Cell line SK-OV-3 Homo sapiens IC50 > 10000.0 nM PMID[21936523]
NPT147 Cell line SK-MEL-2 Homo sapiens IC50 > 10000.0 nM PMID[21936523]
NPT34 Cell line BV-2 Mus musculus IC50 = 52000.0 nM PMID[21936523]
NPT34 Cell line BV-2 Mus musculus Activity = 97.5 % PMID[21936523]

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 NPC111247 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 NPC292056
0.7963 Intermediate Similarity NPC293701
0.7857 Intermediate Similarity NPC163332
0.7818 Intermediate Similarity NPC16208
0.7143 Intermediate Similarity NPC9370
0.7143 Intermediate Similarity NPC287495
0.6897 Remote Similarity NPC194519
0.6897 Remote Similarity NPC601893
0.6833 Remote Similarity NPC481839
0.6557 Remote Similarity NPC147821
0.6557 Remote Similarity NPC319625
0.6557 Remote Similarity NPC183181
0.6557 Remote Similarity NPC41706
0.6452 Remote Similarity NPC476387
0.6452 Remote Similarity NPC237594
0.6452 Remote Similarity NPC119060
0.6316 Remote Similarity NPC310854
0.629 Remote Similarity NPC5851
0.619 Remote Similarity NPC86030
0.6167 Remote Similarity NPC469613
0.6167 Remote Similarity NPC30043
0.6167 Remote Similarity NPC469625
0.5846 Remote Similarity NPC472969
0.5667 Remote Similarity NPC3439
0.5667 Remote Similarity NPC285339
0.5634 Remote Similarity NPC114119
0.5634 Remote Similarity NPC471415
0.5614 Remote Similarity NPC71090
0.5538 Remote Similarity NPC267291
0.549 Remote Similarity NPC137685
0.5469 Remote Similarity NPC7903
0.5469 Remote Similarity NPC160991
0.5385 Remote Similarity NPC75695
0.5312 Remote Similarity NPC58607
0.5312 Remote Similarity NPC191037
0.5312 Remote Similarity NPC178284
0.5256 Remote Similarity NPC143120
0.5224 Remote Similarity NPC605857
0.5195 Remote Similarity NPC138738
0.5167 Remote Similarity NPC469612
0.5167 Remote Similarity NPC469614
0.5156 Remote Similarity NPC203831
0.5128 Remote Similarity NPC470413
0.5077 Remote Similarity NPC114901
0.5077 Remote Similarity NPC48990
0.5072 Remote Similarity NPC470098
0.5072 Remote Similarity NPC473266

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC111247 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