Natural Product: NPC485078

Natural Product IDNPC485078
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 TXDXZFJILUDPDA-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
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 TXDXZFJILUDPDA-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H34O3/c1-3-5-7-9-11-13-15-18-19(21)16-17(23-20(18)22)14-12-10-8-6-4-2/h16,21H,3-15H2,1-2H3
SMILES CCCCCCCCc1c(cc(CCCCCCC)oc1=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   322.25 Volume:   364.381
?
Van der Waals volume.
Dense:   0.884 LogP:   6.173
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.397
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.028
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   13.0 Rigid Bonds:   7.0
TPSA:   50.44
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.47 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.349 Fsp3:   0.75
MCE-18:   7.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.556 Fluc inhibitor:   0.296
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.202
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.284
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.809 Promiscuous compounds:   0.101

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.028 MDCK Permeability:   -4.784
Pgp-inhibitor:   0.102 Pgp-substrate:   0.017
PAMPA:   0.004
?
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):   0.263
20% Bioavailability (F20%):   0.819 30% Bioavailability (F30%):   0.95
50% Bioavailability (F50%):   0.586

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.044 MRP1:   0.976
Plasma Protein Binding (PPB):   99.034% Volume Distribution (VD):   1.143
Fu: 1.068%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.477
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.073
BSEP inhibitor:   0.942

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.025 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.075
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.488
CYP3A4-inhibitor:   0.043 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.88 CYP2C8-inhibitor:   1.0
HLM stability:   0.435
?
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):  4.064 Half-life (T1/2):  0.484

ADMET: Toxicity

hERG Blockers:  0.51 hERG Blockers (10um):  0.879
Human Hepatotoxicity (H-HT):  0.464 Drug-induced Liver Injury (DILI):  0.165
AMES Toxicity:  0.084 Rat Oral Acute Toxicity:  0.259
Maximum Recommended Daily Dose:  0.235 Skin Sensitization:  0.945
Carcinogencity:  0.122 Eye Corrosion:  0.996
Eye Irritation:  0.998 Respiratory Toxicity:  0.973
Drug-induced Neurotoxicity:  0.03 Ototoxicity:  0.127
Hematotoxicity:  0.072 Drug-induced Nephrotoxicity:  0.114
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.068
A549 Cytotoxicity:  0.637 Hek293 Cytotoxicity:  0.423
BCF:   1.278
?
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:   4.785
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.74
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.103
?
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
NPO30084 Pseudomonas sp. Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[11976110]
NPO30084 Pseudomonas sp. Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[12930985]
NPO30084 Pseudomonas sp. Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[16347440]
NPO30084 Pseudomonas sp. Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[2013566]
NPO30084 Pseudomonas sp. Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[22609920]
NPO30084 Pseudomonas sp. Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[25912724]
NPO30084 Pseudomonas sp. Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[28335605]
NPO30084 Pseudomonas sp. Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[28478925]
NPO30084 Pseudomonas sp. Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[8195105]
NPO30084 Pseudomonas sp. Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[9031664]
NPO30084 Pseudomonas sp. Species Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[9157190]
NPO30084 Pseudomonas sp. Species Pseudomonadaceae Bacteria n.a. n.a. n.a. Database[COCONUT]

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
NPT79 Organism Bacillus subtilis Bacillus subtilis IC50 = 24.0 ug.mL-1 PMID[28478925]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus IC50 > 1000.0 ug.mL-1 PMID[28478925]
NPT19 Organism Escherichia coli Escherichia coli IC50 > 1000.0 ug.mL-1 PMID[28478925]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa IC50 > 1000.0 ug.mL-1 PMID[28478925]

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 NPC485078 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 NPC485077
1.0 High Similarity NPC294618
1.0 High Similarity NPC485079
0.9474 High Similarity NPC265050
0.8462 Intermediate Similarity NPC485076
0.75 Intermediate Similarity NPC485075
0.6809 Remote Similarity NPC485070
0.6809 Remote Similarity NPC485071
0.6809 Remote Similarity NPC485072
0.6341 Remote Similarity NPC485074
0.625 Remote Similarity NPC485069
0.6087 Remote Similarity NPC313444
0.5957 Remote Similarity NPC315597
0.5833 Remote Similarity NPC316029
0.5833 Remote Similarity NPC485068
0.5652 Remote Similarity NPC315115
0.56 Remote Similarity NPC316324
0.56 Remote Similarity NPC315394
0.5208 Remote Similarity NPC485067

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC485078 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