Natural Product: NPC75039

Natural Product IDNPC75039
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KGQIYLSVVQCRJA-INIZCTEOSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11660490
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002650] Diarylheptanoids
        • [CHEMONTID:0002651] Linear diarylheptanoids

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 KGQIYLSVVQCRJA-INIZCTEOSA-N
Standard InCHI InChI=1S/C20H24O6/c1-26-16(7-3-14-5-9-18(23)20(25)11-14)12-15(21)6-2-13-4-8-17(22)19(24)10-13/h4-5,8-11,16,22-25H,2-3,6-7,12H2,1H3/t16-/m0/s1
SMILES CO[C@@H](CCc1ccc(c(c1)O)O)CC(=O)CCc1ccc(c(c1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   360.16 Volume:   371.649
?
Van der Waals volume.
Dense:   0.969 LogP:   1.99
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.256
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.967
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The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   13.0
TPSA:   107.22
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.512 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.948 Fsp3:   0.35
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:   1
Colloidal aggregators:   0.389 Fluc inhibitor:   0.31
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.177
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.256
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.652 Promiscuous compounds:   0.159

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.026 MDCK Permeability:   -4.756
Pgp-inhibitor:   0.933 Pgp-substrate:   0.035
PAMPA:   0.031
?
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):   0.003
20% Bioavailability (F20%):   0.988 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.029
Plasma Protein Binding (PPB):   77.588% Volume Distribution (VD):   -0.21
Fu: 22.118%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   0.98 BCRP inhibitor:   0.873
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.792 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   0.951 CYP2C19-substrate:   0.378
CYP2C9-inhibitor:   0.995 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.733 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.777
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.99
?
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):  18.924 Half-life (T1/2):  1.773

ADMET: Toxicity

hERG Blockers:  0.178 hERG Blockers (10um):  0.869
Human Hepatotoxicity (H-HT):  0.69 Drug-induced Liver Injury (DILI):  0.142
AMES Toxicity:  0.362 Rat Oral Acute Toxicity:  0.086
Maximum Recommended Daily Dose:  0.828 Skin Sensitization:  0.999
Carcinogencity:  0.18 Eye Corrosion:  0.226
Eye Irritation:  0.99 Respiratory Toxicity:  0.113
Drug-induced Neurotoxicity:  0.077 Ototoxicity:  0.902
Hematotoxicity:  0.058 Drug-induced Nephrotoxicity:  0.279
Genotoxicity:  0.271 RPMI-8226 Immunitoxicity:  0.01
A549 Cytotoxicity:  0.801 Hek293 Cytotoxicity:  0.194
BCF:   1.365
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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:   4.055
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.227
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.829
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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
NPO15361 Alnus japonica Species Betulaceae Eukaryota bark n.a. n.a. PMID[20045319]
NPO15361 Alnus japonica Species Betulaceae Eukaryota n.a. n.a. n.a. PMID[26341132]
NPO15361 Alnus japonica Species Betulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15361 Alnus japonica Species Betulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15361 Alnus japonica Species Betulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15361 Alnus japonica Species Betulaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15361 Alnus japonica Species Betulaceae 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
NPT737 Cell line HUVEC Homo sapiens Inhibition = 21.0 % PMID[33422907]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 14500.0 nM PMID[33422907]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 60.0 % PMID[33422907]
NPT737 Cell line HUVEC Homo sapiens Inhibition = 77.0 % PMID[33422907]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 37.0 % PMID[33422907]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 11400.0 nM PMID[33422907]
NPT28833 No target No relevant target n.a. IC50 = 28300.0 nM PMID[33422907]

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 NPC75039 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 NPC98305
0.6591 Remote Similarity NPC70084
0.6296 Remote Similarity NPC103398
0.6296 Remote Similarity NPC608691
0.619 Remote Similarity NPC231591
0.619 Remote Similarity NPC610842
0.6182 Remote Similarity NPC293686
0.6042 Remote Similarity NPC86198
0.6 Remote Similarity NPC186970
0.5862 Remote Similarity NPC158325
0.5862 Remote Similarity NPC193018
0.5745 Remote Similarity NPC34634
0.5686 Remote Similarity NPC109371
0.5667 Remote Similarity NPC180171
0.5472 Remote Similarity NPC200988
0.5472 Remote Similarity NPC145023
0.5455 Remote Similarity NPC148969
0.5435 Remote Similarity NPC61062
0.5385 Remote Similarity NPC23402
0.5294 Remote Similarity NPC265454
0.5273 Remote Similarity NPC470215
0.5273 Remote Similarity NPC470214
0.5088 Remote Similarity NPC610
0.5088 Remote Similarity NPC175799
0.5075 Remote Similarity NPC473138

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC75039 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