Natural Product: NPC166137

Natural Product IDNPC166137
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NFAAULYTGYCSKM-LSDHHAIUSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3309442
PubChem CID NA
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:0001613] Dibenzylbutyrolactone 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 NFAAULYTGYCSKM-LSDHHAIUSA-N
Standard InCHI InChI=1S/C20H20O6/c1-23-18-8-12(2-4-16(18)21)6-14-10-24-20(22)15(14)7-13-3-5-17-19(9-13)26-11-25-17/h2-5,8-9,14-15,21H,6-7,10-11H2,1H3/t14-,15+/m0/s1
SMILES COc1cc(ccc1O)C[C@H]1COC(=O)[C@@H]1Cc1ccc2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.13 Volume:   354.536
?
Van der Waals volume.
Dense:   1.004 LogP:   2.256
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.354
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.741
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   22.0
TPSA:   74.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.831 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.192 Fsp3:   0.35
MCE-18:   69.222
?
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:   0.405 Fluc inhibitor:   0.447
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.026
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.179
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.251 Promiscuous compounds:   0.424

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.804 MDCK Permeability:   -4.597
Pgp-inhibitor:   0.75 Pgp-substrate:   0.031
PAMPA:   0.042
?
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):   0.001
20% Bioavailability (F20%):   0.627 30% Bioavailability (F30%):   0.11
50% Bioavailability (F50%):   0.907

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.008 MRP1:   0.699
Plasma Protein Binding (PPB):   97.975% Volume Distribution (VD):   -0.453
Fu: 2.099%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.016
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.607 CYP1A2-substrate:   0.994
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.328 CYP2C9-substrate:   0.999
CYP2D6-inhibitor:   0.023 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.998 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.997
HLM stability:   0.971
?
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):  4.402 Half-life (T1/2):  1.255

ADMET: Toxicity

hERG Blockers:  0.258 hERG Blockers (10um):  0.627
Human Hepatotoxicity (H-HT):  0.939 Drug-induced Liver Injury (DILI):  0.982
AMES Toxicity:  0.763 Rat Oral Acute Toxicity:  0.612
Maximum Recommended Daily Dose:  0.706 Skin Sensitization:  0.98
Carcinogencity:  0.791 Eye Corrosion:  0.003
Eye Irritation:  0.9 Respiratory Toxicity:  0.559
Drug-induced Neurotoxicity:  0.905 Ototoxicity:  0.668
Hematotoxicity:  0.719 Drug-induced Nephrotoxicity:  0.943
Genotoxicity:  0.997 RPMI-8226 Immunitoxicity:  0.262
A549 Cytotoxicity:  0.582 Hek293 Cytotoxicity:  0.696
BCF:   1.454
?
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:   4.096
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.341
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.84
?
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
NPO7067 Stellera chamaejasme Species Thymelaeaceae Eukaryota n.a. root n.a. PMID[15997133]
NPO7067 Stellera chamaejasme Species Thymelaeaceae Eukaryota n.a. root n.a. PMID[16141313]
NPO7067 Stellera chamaejasme Species Thymelaeaceae Eukaryota n.a. callus n.a. PMID[22368856]
NPO7067 Stellera chamaejasme Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[23611151]
NPO7067 Stellera chamaejasme Species Thymelaeaceae Eukaryota roots n.a. n.a. PMID[24931277]
NPO7067 Stellera chamaejasme Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[26562066]
NPO7067 Stellera chamaejasme Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[34770847]
NPO7067 Stellera chamaejasme Species Thymelaeaceae Eukaryota n.a. root n.a. Database[Article]
NPO7067 Stellera chamaejasme Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28392 Macrosiphum liriodendri Species Aphididae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28510 Aspergillus pseudodeflectus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28218 Asplenium adiantum-nigrum Species Aspleniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9031 Euonymus europaeus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1040 Ficus conraui Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO103 Stereocaulon salazinum Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO617 Vicia balansae Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7067 Stellera chamaejasme Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9031 Euonymus europaeus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9031 Euonymus europaeus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7067 Stellera chamaejasme Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7067 Stellera chamaejasme Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7067 Stellera chamaejasme Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO103 Stereocaulon salazinum Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9031 Euonymus europaeus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO617 Vicia balansae Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28510 Aspergillus pseudodeflectus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28392 Macrosiphum liriodendri Species Aphididae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28218 Asplenium adiantum-nigrum Species Aspleniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1040 Ficus conraui Species Moraceae 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
NPT81 Cell line A549 Homo sapiens IC50 = 273.0 nM PMID[24931277]

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 NPC166137 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 NPC282291
0.8475 Intermediate Similarity NPC216223
0.8393 Intermediate Similarity NPC300776
0.8393 Intermediate Similarity NPC176814
0.8393 Intermediate Similarity NPC4982
0.8393 Intermediate Similarity NPC606629
0.8276 Intermediate Similarity NPC145569
0.7963 Intermediate Similarity NPC68779
0.7963 Intermediate Similarity NPC108598
0.7833 Intermediate Similarity NPC487679
0.7833 Intermediate Similarity NPC487678
0.7759 Intermediate Similarity NPC106920
0.7759 Intermediate Similarity NPC15811
0.7679 Intermediate Similarity NPC205915
0.7593 Intermediate Similarity NPC110958
0.7593 Intermediate Similarity NPC19890
0.7414 Intermediate Similarity NPC176586
0.7414 Intermediate Similarity NPC210354
0.7414 Intermediate Similarity NPC273657
0.7288 Intermediate Similarity NPC191158
0.7288 Intermediate Similarity NPC177644
0.7231 Intermediate Similarity NPC478703
0.7231 Intermediate Similarity NPC478704
0.6875 Remote Similarity NPC169973
0.6774 Remote Similarity NPC293757
0.6774 Remote Similarity NPC668
0.6724 Remote Similarity NPC274356
0.6724 Remote Similarity NPC101748
0.6613 Remote Similarity NPC5310
0.6429 Remote Similarity NPC223807
0.6271 Remote Similarity NPC92693
0.6269 Remote Similarity NPC174512
0.6267 Remote Similarity NPC299706
0.6267 Remote Similarity NPC115466
0.6267 Remote Similarity NPC61604
0.6167 Remote Similarity NPC40237
0.6167 Remote Similarity NPC487680
0.6094 Remote Similarity NPC487677
0.6094 Remote Similarity NPC487675
0.6 Remote Similarity NPC487681
0.6 Remote Similarity NPC211386
0.5965 Remote Similarity NPC476748
0.5938 Remote Similarity NPC102908
0.5902 Remote Similarity NPC143895
0.5857 Remote Similarity NPC478705
0.5758 Remote Similarity NPC100675
0.5758 Remote Similarity NPC601691
0.5735 Remote Similarity NPC56184
0.5606 Remote Similarity NPC46880
0.5606 Remote Similarity NPC3982
0.5588 Remote Similarity NPC471505
0.5574 Remote Similarity NPC474288
0.5556 Remote Similarity NPC604694
0.5517 Remote Similarity NPC31344
0.5517 Remote Similarity NPC317769
0.5517 Remote Similarity NPC72796
0.5441 Remote Similarity NPC106739
0.5441 Remote Similarity NPC161249
0.5373 Remote Similarity NPC110699
0.5373 Remote Similarity NPC106055
0.5362 Remote Similarity NPC31751
0.5345 Remote Similarity NPC600801
0.5333 Remote Similarity NPC227217
0.5333 Remote Similarity NPC117780
0.5323 Remote Similarity NPC192255
0.5294 Remote Similarity NPC606339
0.525 Remote Similarity NPC245615
0.5217 Remote Similarity NPC485282
0.5217 Remote Similarity NPC67247
0.5217 Remote Similarity NPC485283
0.5217 Remote Similarity NPC485281
0.5217 Remote Similarity NPC610284
0.5161 Remote Similarity NPC607444
0.5156 Remote Similarity NPC158737
0.5156 Remote Similarity NPC173308
0.5156 Remote Similarity NPC181079
0.5152 Remote Similarity NPC284464
0.507 Remote Similarity NPC76687

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC166137 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