Natural Product: NPC116200

Natural Product IDNPC116200
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 YAIYRXPNTQJXBE-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 71719401
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0004155] Diphenylethers

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 YAIYRXPNTQJXBE-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H16O5/c1-9-4-11(17)7-12(5-9)21-13-6-10(2)15(14(18)8-13)16(19)20-3/h4-8,17-18H,1-3H3
SMILES Cc1cc(cc(c1)Oc1cc(C)c(c(c1)O)C(=O)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   288.1 Volume:   293.675
?
Van der Waals volume.
Dense:   0.981 LogP:   3.721
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.301
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.175
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   13.0
TPSA:   75.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.847 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.252 Fsp3:   0.188
MCE-18:   14.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.296 Fluc inhibitor:   0.15
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.074
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.539
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.6 Promiscuous compounds:   0.135

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.932 MDCK Permeability:   -4.862
Pgp-inhibitor:   0.127 Pgp-substrate:   0.14
PAMPA:   0.194
?
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%):   0.033 30% Bioavailability (F30%):   0.401
50% Bioavailability (F50%):   0.905

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.17 MRP1:   0.958
Plasma Protein Binding (PPB):   96.371% Volume Distribution (VD):   -0.368
Fu: 3.819%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.549
BSEP inhibitor:   0.73

ADMET: Metabolism

CYP1A2-inhibitor:   0.506 CYP1A2-substrate:   0.984
CYP2C19-inhibitor:   0.006 CYP2C19-substrate:   0.87
CYP2C9-inhibitor:   0.946 CYP2C9-substrate:   0.981
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.945
CYP3A4-inhibitor:   0.385 CYP3A4-substrate:   0.015
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.998
?
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):  5.192 Half-life (T1/2):  1.184

ADMET: Toxicity

hERG Blockers:  0.165 hERG Blockers (10um):  0.739
Human Hepatotoxicity (H-HT):  0.206 Drug-induced Liver Injury (DILI):  0.559
AMES Toxicity:  0.447 Rat Oral Acute Toxicity:  0.12
Maximum Recommended Daily Dose:  0.41 Skin Sensitization:  0.556
Carcinogencity:  0.727 Eye Corrosion:  0.031
Eye Irritation:  0.995 Respiratory Toxicity:  0.56
Drug-induced Neurotoxicity:  0.249 Ototoxicity:  0.161
Hematotoxicity:  0.044 Drug-induced Nephrotoxicity:  0.082
Genotoxicity:  0.204 RPMI-8226 Immunitoxicity:  0.048
A549 Cytotoxicity:  0.205 Hek293 Cytotoxicity:  0.676
BCF:   1.221
?
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:   3.992
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.901
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.392
?
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
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota rhizosphere Sonoran desert n.a. PMID[15620238]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[17542490]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[17564467]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[19053517]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21366228]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21718031]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21854017]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota healthy leaf of Ginkgo biloba campus of Nanjing University, Nanjing, China 2008-OCT PMID[22196792]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota isolated from the sponge Xestospongia testudinaria n.a. n.a. PMID[22225637]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota Isolated from a sandy-loam soil sample 50 m inland from Waikiki Beach, Honolulu, Hawaii 2010-JUL PMID[22400916]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[22703109]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23527875]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[24050204]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[25001296]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[25581396]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[26273902]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[31012585]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[33305943]

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
NPT116 Cell line HL-60 Homo sapiens IC50 > 10000.0 nM PMID[23527875]
NPT111 Cell line K562 Homo sapiens IC50 = 5940.0 nM PMID[23527875]
NPT1311 Organism Listonella anguillarum Listonella anguillarum MIC = 21700.0 nM PMID[23527875]
NPT2911 Organism Pseudomonas putida Pseudomonas putida MIC = 21700.0 nM PMID[23527875]
NPT565 Organism Vibrio parahaemolyticus Vibrio parahaemolyticus MIC = 21700.0 nM PMID[23527875]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 10900.0 nM PMID[23527875]
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MIC = 2710.0 nM PMID[23527875]

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 NPC116200 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
0.7333 Intermediate Similarity NPC606909
0.6667 Remote Similarity NPC255068
0.5556 Remote Similarity NPC298134
0.5476 Remote Similarity NPC180905
0.5366 Remote Similarity NPC189823
0.5106 Remote Similarity NPC216836
0.5102 Remote Similarity NPC487980

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC116200 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