Natural Product: NPC119060

Natural Product IDNPC119060
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Threo-(7R,8R)-Guaiacylglycerol-B-Coniferyl Aldehyde Ether
IUPAC Name (E)-3-[4-[(1R,2R)-1,3-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)propan-2-yl]oxy-3-methoxyphenyl]prop-2-enal
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2430311
PubChem CID 21582571
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 LWLOALZBDOVWAE-FMEUAVTJSA-N
Standard InCHI InChI=1S/C20H22O7/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/h3-11,19-20,22-24H,12H2,1-2H3/b4-3+/t19-,20-/m1/s1
SMILES COc1cc(ccc1O)[C@H]([C@@H](CO)Oc1ccc(/C=C/C=O)cc1OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.14 Volume:   377.803
?
Van der Waals volume.
Dense:   0.99 LogP:   1.288
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.552
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.607
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   14.0
TPSA:   105.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.456 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.285 Fsp3:   0.25
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:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.78 Fluc inhibitor:   0.962
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.047
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.447
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.343 Promiscuous compounds:   0.47

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.308 MDCK Permeability:   -5.07
Pgp-inhibitor:   0.55 Pgp-substrate:   0.008
PAMPA:   0.544
?
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%):   0.244 30% Bioavailability (F30%):   0.331
50% Bioavailability (F50%):   0.925

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.015
Plasma Protein Binding (PPB):   82.319% Volume Distribution (VD):   0.035
Fu: 19.048%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.691
BSEP inhibitor:   0.991

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.829 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.616
CYP2D6-inhibitor:   0.996 CYP2D6-substrate:   0.04
CYP3A4-inhibitor:   0.007 CYP3A4-substrate:   0.004
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.982
HLM stability:   0.051
?
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):  7.856 Half-life (T1/2):  1.559

ADMET: Toxicity

hERG Blockers:  0.085 hERG Blockers (10um):  0.403
Human Hepatotoxicity (H-HT):  0.667 Drug-induced Liver Injury (DILI):  0.186
AMES Toxicity:  0.691 Rat Oral Acute Toxicity:  0.213
Maximum Recommended Daily Dose:  0.245 Skin Sensitization:  0.639
Carcinogencity:  0.317 Eye Corrosion:  0.001
Eye Irritation:  0.578 Respiratory Toxicity:  0.158
Drug-induced Neurotoxicity:  0.559 Ototoxicity:  0.736
Hematotoxicity:  0.117 Drug-induced Nephrotoxicity:  0.76
Genotoxicity:  0.528 RPMI-8226 Immunitoxicity:  0.082
A549 Cytotoxicity:  0.095 Hek293 Cytotoxicity:  0.155
BCF:   0.879
?
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:   3.492
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.957
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.448
?
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
NPO12011 Crataegus pinnatifida Species Rosaceae Eukaryota n.a. fruit n.a. PMID[15739361]
NPO12011 Crataegus pinnatifida Species Rosaceae Eukaryota n.a. seed n.a. PMID[23845552]
NPO12011 Crataegus pinnatifida Species Rosaceae Eukaryota seeds n.a. n.a. PMID[23999046]
NPO12011 Crataegus pinnatifida Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12011 Crataegus pinnatifida Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12011 Crataegus pinnatifida Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12011 Crataegus pinnatifida Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12011 Crataegus pinnatifida Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO12011 Crataegus pinnatifida Species Rosaceae 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
NPT171 Cell line MRC5 Homo sapiens IC50 > 50000.0 nM PMID[23999046]
NPT111 Cell line K562 Homo sapiens IC50 > 50000.0 nM PMID[23999046]
NPT466 Cell line U-937 Homo sapiens IC50 > 50000.0 nM PMID[23999046]
NPT116 Cell line HL-60 Homo sapiens IC50 = 33530.0 nM PMID[23999046]
NPT453 Cell line HT-1080 Homo sapiens IC50 = 33020.0 nM PMID[23999046]
NPT81 Cell line A549 Homo sapiens IC50 = 25520.0 nM PMID[23999046]
NPT393 Cell line HCT-116 Homo sapiens IC50 = 27340.0 nM PMID[23999046]
NPT65 Cell line HepG2 Homo sapiens IC50 = 38640.0 nM PMID[23999046]
NPT83 Cell line MCF7 Homo sapiens IC50 > 50000.0 nM PMID[23999046]
NPT165 Cell line HeLa Homo sapiens IC50 > 50000.0 nM PMID[23999046]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 34190.0 nM PMID[23999046]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 1050.0 nM PMID[26774654]

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 NPC119060 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 NPC476387
1.0 High Similarity NPC237594
0.8393 Intermediate Similarity NPC147821
0.8393 Intermediate Similarity NPC319625
0.8393 Intermediate Similarity NPC183181
0.8393 Intermediate Similarity NPC41706
0.807 Intermediate Similarity NPC267291
0.6949 Remote Similarity NPC58607
0.6949 Remote Similarity NPC191037
0.6949 Remote Similarity NPC178284
0.6897 Remote Similarity NPC9370
0.6897 Remote Similarity NPC287495
0.6774 Remote Similarity NPC249791
0.6667 Remote Similarity NPC114901
0.6667 Remote Similarity NPC48990
0.6667 Remote Similarity NPC601893
0.6557 Remote Similarity NPC7903
0.6557 Remote Similarity NPC160991
0.6494 Remote Similarity NPC470827
0.6452 Remote Similarity NPC111247
0.6452 Remote Similarity NPC292056
0.6438 Remote Similarity NPC470413
0.6133 Remote Similarity NPC470769
0.5974 Remote Similarity NPC470828
0.5833 Remote Similarity NPC310854
0.5741 Remote Similarity NPC39793
0.5672 Remote Similarity NPC224876
0.5672 Remote Similarity NPC472969
0.5606 Remote Similarity NPC481839
0.5479 Remote Similarity NPC114119
0.5479 Remote Similarity NPC471415
0.5455 Remote Similarity NPC83375
0.5441 Remote Similarity NPC118787
0.5395 Remote Similarity NPC107145
0.5385 Remote Similarity NPC16208
0.5325 Remote Similarity NPC473909
0.5224 Remote Similarity NPC163332
0.5224 Remote Similarity NPC75695
0.5152 Remote Similarity NPC214729
0.5152 Remote Similarity NPC479110
0.5094 Remote Similarity NPC179309
0.5063 Remote Similarity NPC260397

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC119060 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