Natural Product: NPC37286

Natural Product IDNPC37286
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 BROWXLHOQNBXKJ-RDJZCZTQSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 102508666
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0002545] Coumarinolignans

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 BROWXLHOQNBXKJ-RDJZCZTQSA-N
Standard InCHI InChI=1S/C19H16O7/c1-23-14-8-11(2-5-12(14)21)17-15(9-20)24-13-6-3-10-4-7-16(22)25-18(10)19(13)26-17/h2-8,15,17,20-21H,9H2,1H3/t15-,17-/m0/s1
SMILES COc1cc(ccc1O)[C@H]1[C@H](CO)Oc2ccc3ccc(=O)oc3c2O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.09 Volume:   343.394
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Van der Waals volume.
Dense:   1.037 LogP:   2.17
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.229
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.16
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   23.0
TPSA:   98.36
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.695 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.386 Fsp3:   0.211
MCE-18:   69.826
?
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:   0.665 Fluc inhibitor:   0.8
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.931
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.298
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.241 Promiscuous compounds:   0.555

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.735 MDCK Permeability:   -5.098
Pgp-inhibitor:   0.005 Pgp-substrate:   0.001
PAMPA:   0.34
?
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%):   0.545 30% Bioavailability (F30%):   0.501
50% Bioavailability (F50%):   0.603

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.986
Plasma Protein Binding (PPB):   91.16% Volume Distribution (VD):   -0.086
Fu: 8.607%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.001
BSEP inhibitor:   0.977

ADMET: Metabolism

CYP1A2-inhibitor:   0.774 CYP1A2-substrate:   0.025
CYP2C19-inhibitor:   0.027 CYP2C19-substrate:   0.045
CYP2C9-inhibitor:   0.808 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.014 CYP2D6-substrate:   0.995
CYP3A4-inhibitor:   0.798 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.998
HLM stability:   0.028
?
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):  6.613 Half-life (T1/2):  1.106

ADMET: Toxicity

hERG Blockers:  0.08 hERG Blockers (10um):  0.232
Human Hepatotoxicity (H-HT):  0.675 Drug-induced Liver Injury (DILI):  0.742
AMES Toxicity:  0.64 Rat Oral Acute Toxicity:  0.364
Maximum Recommended Daily Dose:  0.203 Skin Sensitization:  0.839
Carcinogencity:  0.556 Eye Corrosion:  0.079
Eye Irritation:  0.949 Respiratory Toxicity:  0.488
Drug-induced Neurotoxicity:  0.328 Ototoxicity:  0.322
Hematotoxicity:  0.27 Drug-induced Nephrotoxicity:  0.349
Genotoxicity:  0.893 RPMI-8226 Immunitoxicity:  0.116
A549 Cytotoxicity:  0.135 Hek293 Cytotoxicity:  0.299
BCF:   0.765
?
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:   3.474
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.642
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.102
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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
NPO12339 Daphne feddei Species Thymelaeaceae Eukaryota stem bark Kunming, Yunnan Province, China n.a. PMID[18986199]
NPO23754 Solanum aculeatissimum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12339 Daphne feddei Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21329 Ilyonectria destructans Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10211 Pajanelia multijuga n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO23754 Solanum aculeatissimum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21329 Ilyonectria destructans Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23754 Solanum aculeatissimum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10211 Pajanelia multijuga n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO12339 Daphne feddei Species Thymelaeaceae 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

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 NPC37286 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
0.8906 High Similarity NPC476347
0.7826 Intermediate Similarity NPC120426
0.7206 Intermediate Similarity NPC187398
0.6901 Remote Similarity NPC476348
0.6528 Remote Similarity NPC21184
0.6301 Remote Similarity NPC205727
0.6216 Remote Similarity NPC485419
0.6216 Remote Similarity NPC485418
0.6203 Remote Similarity NPC30688
0.5972 Remote Similarity NPC15577
0.5765 Remote Similarity NPC120774
0.5714 Remote Similarity NPC476352
0.5584 Remote Similarity NPC294522
0.5568 Remote Similarity NPC264875
0.5568 Remote Similarity NPC163598
0.5476 Remote Similarity NPC215060
0.5467 Remote Similarity NPC485421
0.5467 Remote Similarity NPC485417
0.5467 Remote Similarity NPC485416
0.5467 Remote Similarity NPC485420
0.5205 Remote Similarity NPC5851
0.5195 Remote Similarity NPC176903
0.5176 Remote Similarity NPC14662
0.5176 Remote Similarity NPC478720
0.5135 Remote Similarity NPC86030

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC37286 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