Natural Product: NPC488580

Natural Product IDNPC488580
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JVOZREUKQVHZCO-OQIJWPOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 132487819
Chemical Classification
  • CHEMONTID:0000000 [Organic 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 JVOZREUKQVHZCO-OQIJWPOYSA-N
Standard InCHI InChI=1S/C19H20O7/c20-13-3-1-9-5-11(13)12-6-10(2-4-14(12)21)8-16(23)18(25)19(26)17(24)15(22)7-9/h1-6,15,17-22,24-26H,7-8H2/t15-,17-,18+,19-/m1/s1
SMILES c1cc(c2-c3cc(ccc3O)CC(=O)[C@@H]([C@@H]([C@@H]([C@@H](Cc1c2)O)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   360.12 Volume:   354.587
?
Van der Waals volume.
Dense:   1.016 LogP:   0.279
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.782
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.306
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   22.0
TPSA:   138.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   6.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.385 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.554 Fsp3:   0.316
MCE-18:   69.6
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.528 Fluc inhibitor:   0.096
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.493
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.189
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.368 Promiscuous compounds:   0.113

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.563 MDCK Permeability:   -4.65
Pgp-inhibitor:   0.0 Pgp-substrate:   0.427
PAMPA:   1.0
?
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):   0.0
20% Bioavailability (F20%):   0.027 30% Bioavailability (F30%):   0.037
50% Bioavailability (F50%):   0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.088
Plasma Protein Binding (PPB):   78.715% Volume Distribution (VD):   -0.284
Fu: 22.238%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.946
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.002
BSEP inhibitor:   0.925

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.022
CYP2C9-inhibitor:   0.145 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.027
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.997
HLM stability:   0.931
?
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):  5.214 Half-life (T1/2):  3.181

ADMET: Toxicity

hERG Blockers:  0.07 hERG Blockers (10um):  0.415
Human Hepatotoxicity (H-HT):  0.348 Drug-induced Liver Injury (DILI):  0.031
AMES Toxicity:  0.557 Rat Oral Acute Toxicity:  0.114
Maximum Recommended Daily Dose:  0.308 Skin Sensitization:  0.067
Carcinogencity:  0.11 Eye Corrosion:  0.0
Eye Irritation:  0.479 Respiratory Toxicity:  0.119
Drug-induced Neurotoxicity:  0.013 Ototoxicity:  0.95
Hematotoxicity:  0.137 Drug-induced Nephrotoxicity:  0.556
Genotoxicity:  0.32 RPMI-8226 Immunitoxicity:  0.163
A549 Cytotoxicity:  0.177 Hek293 Cytotoxicity:  0.348
BCF:   0.738
?
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:   3.096
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.271
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.744
?
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
NPO12631 Corylus avellana Species Betulaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s10616-014-9808-y]
NPO12631 Corylus avellana Species Betulaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.stress.2021.100038]
NPO12631 Corylus avellana Species Betulaceae Eukaryota Shells; Leaves n.a. n.a. PMID[18163585]
NPO12631 Corylus avellana Species Betulaceae Eukaryota n.a. n.a. n.a. PMID[25420236]
NPO12631 Corylus avellana Species Betulaceae Eukaryota Leaves n.a. n.a. PMID[26606246]
NPO12631 Corylus avellana Species Betulaceae Eukaryota Green Leafy Covers n.a. n.a. PMID[28520428]
NPO12631 Corylus avellana Species Betulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12631 Corylus avellana Species Betulaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO12631 Corylus avellana Species Betulaceae Eukaryota n.a. n.a. Database[FooDB]
NPO12631 Corylus avellana 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
NPT621 Tissue Plasma Homo sapiens Inhibition = 14.4 % PMID[28520428]
NPT621 Tissue Plasma Homo sapiens Inhibition = 33.3 % PMID[28520428]
NPT19 Organism Escherichia coli Escherichia coli IZ = 4.67 mm PMID[28520428]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa IZ = 5.0 mm PMID[28520428]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus IZ = 6.33 mm PMID[28520428]
NPT19 Organism Escherichia coli Escherichia coli IZ = 10.0 mm PMID[28520428]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa IZ = 8.67 mm PMID[28520428]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus IZ = 10.0 mm PMID[28520428]
NPT19 Organism Escherichia coli Escherichia coli IZ = 10.33 mm PMID[28520428]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa IZ = 10.0 mm PMID[28520428]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus IZ = 10.67 mm PMID[28520428]
NPT19 Organism Escherichia coli Escherichia coli MIC = 10.0 ug PMID[28520428]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC = 10.0 ug PMID[28520428]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 30.0 ug PMID[28520428]
NPT314 Organism Bacillus cereus Bacillus cereus IZ = 5.67 mm PMID[28520428]
NPT314 Organism Bacillus cereus Bacillus cereus IZ = 9.67 mm PMID[28520428]
NPT314 Organism Bacillus cereus Bacillus cereus IZ = 11.33 mm PMID[28520428]
NPT314 Organism Bacillus cereus Bacillus cereus IZ = 10.67 mm PMID[28520428]
NPT314 Organism Bacillus cereus Bacillus cereus MIC = 5.0 ug PMID[28520428]

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 NPC488580 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
0.725 Intermediate Similarity NPC488678
0.6957 Remote Similarity NPC611070
0.6667 Remote Similarity NPC488578
0.6667 Remote Similarity NPC231767
0.6667 Remote Similarity NPC608772
0.6383 Remote Similarity NPC488677
0.5957 Remote Similarity NPC488674
0.5918 Remote Similarity NPC127975
0.5778 Remote Similarity NPC473137
0.5686 Remote Similarity NPC608771
0.54 Remote Similarity NPC31936
0.5208 Remote Similarity NPC473136
0.5192 Remote Similarity NPC488675
0.5094 Remote Similarity NPC601260

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC488580 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