Natural Product: NPC59506

Natural Product IDNPC59506
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KLAVUSHQLJDZCS-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 129673055
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000134] Phenols
        • [CHEMONTID:0001286] Benzenediols
          • [CHEMONTID:0000137] Resorcinols

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 KLAVUSHQLJDZCS-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H32O2/c1-3-5-7-9-10-12-16-14-18(20)17(19(21)15-16)13-11-8-6-4-2/h14-15,20-21H,3-13H2,1-2H3
SMILES CCCCCCCc1cc(c(CCCCCC)c(c1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   292.24 Volume:   338.295
?
Van der Waals volume.
Dense:   0.864 LogP:   7.251
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.459
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.643
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   11.0 Rigid Bonds:   6.0
TPSA:   40.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.511 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.151 Fsp3:   0.684
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:   0.713 Fluc inhibitor:   0.06
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.014
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.012
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.961 Promiscuous compounds:   0.105

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.027 MDCK Permeability:   -4.751
Pgp-inhibitor:   0.931 Pgp-substrate:   0.11
PAMPA:   0.009
?
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):   0.116
20% Bioavailability (F20%):   0.819 30% Bioavailability (F30%):   0.918
50% Bioavailability (F50%):   0.957

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.835 MRP1:   0.713
Plasma Protein Binding (PPB):   99.101% Volume Distribution (VD):   1.19
Fu: 1.119%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.523
OATP1B3 inhibitor:   0.828 BCRP inhibitor:   0.902
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.28 CYP1A2-substrate:   0.982
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.98
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.013
CYP2D6-inhibitor:   0.926 CYP2D6-substrate:   0.952
CYP3A4-inhibitor:   0.987 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.225 CYP2C8-inhibitor:   1.0
HLM stability:   0.773
?
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):  4.381 Half-life (T1/2):  0.595

ADMET: Toxicity

hERG Blockers:  0.703 hERG Blockers (10um):  0.944
Human Hepatotoxicity (H-HT):  0.504 Drug-induced Liver Injury (DILI):  0.027
AMES Toxicity:  0.067 Rat Oral Acute Toxicity:  0.233
Maximum Recommended Daily Dose:  0.177 Skin Sensitization:  0.97
Carcinogencity:  0.017 Eye Corrosion:  0.994
Eye Irritation:  0.998 Respiratory Toxicity:  0.992
Drug-induced Neurotoxicity:  0.021 Ototoxicity:  0.246
Hematotoxicity:  0.062 Drug-induced Nephrotoxicity:  0.207
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.122
A549 Cytotoxicity:  0.904 Hek293 Cytotoxicity:  0.649
BCF:   1.713
?
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:   4.804
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.592
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.592
?
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
NPO8493 Capraria biflora Species Scrophulariaceae Eukaryota n.a. n.a. n.a. PMID[11087595]
NPO8881 Centipeda minima Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[23189738]
NPO5119.1 Pseudomonas chlororaphis subsp. aurantiaca Subspecies Pseudomonadaceae Bacteria n.a. n.a. n.a. PMID[31999458]
NPO21339 Upuna borneensis Species Dipterocarpaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8493 Capraria biflora Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11075 Aglaia tomentosa Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8881 Centipeda minima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10032 Backhousia citriodora Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8881 Centipeda minima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11075 Aglaia tomentosa Species Meliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8881 Centipeda minima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21339 Upuna borneensis Species Dipterocarpaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8881 Centipeda minima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8881 Centipeda minima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10032 Backhousia citriodora Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18405 Trichoderma avellaneum Species Hypocreaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8239 Mentha timija Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11075 Aglaia tomentosa Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8881 Centipeda minima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21339 Upuna borneensis Species Dipterocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5119.1 Pseudomonas chlororaphis subsp. aurantiaca Subspecies Pseudomonadaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO1807 Senecio macrocephalus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8493 Capraria biflora Species Scrophulariaceae 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
NPT878 Organism Streptococcus mutans Streptococcus mutans MIC = 33.4 ug.mL-1 PMID[31999458]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 66.7 ug.mL-1 PMID[31999458]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 1.1 ug.mL-1 PMID[31999458]
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MIC = 8.3 ug.mL-1 PMID[31999458]
NPT3721 Organism Enterococcus hirae Enterococcus hirae MIC = 33.4 ug.mL-1 PMID[31999458]

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 NPC59506 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
0.931 High Similarity NPC37802
0.8667 High Similarity NPC244513
0.7188 Intermediate Similarity NPC227458
0.7097 Intermediate Similarity NPC218879
0.6667 Remote Similarity NPC294186
0.6667 Remote Similarity NPC147310
0.6667 Remote Similarity NPC137415
0.6667 Remote Similarity NPC166313
0.6667 Remote Similarity NPC192032
0.6667 Remote Similarity NPC24407
0.6667 Remote Similarity NPC11280
0.6316 Remote Similarity NPC232523
0.6286 Remote Similarity NPC488411
0.6286 Remote Similarity NPC488410
0.6286 Remote Similarity NPC488409
0.5897 Remote Similarity NPC486908
0.5758 Remote Similarity NPC246056
0.5714 Remote Similarity NPC123273
0.5714 Remote Similarity NPC318325
0.5676 Remote Similarity NPC3358
0.5676 Remote Similarity NPC306884
0.5676 Remote Similarity NPC603092
0.5641 Remote Similarity NPC146798
0.5641 Remote Similarity NPC222522
0.5641 Remote Similarity NPC106396
0.5641 Remote Similarity NPC94351
0.5641 Remote Similarity NPC168303
0.5476 Remote Similarity NPC158253
0.5476 Remote Similarity NPC252105
0.5385 Remote Similarity NPC53051
0.5385 Remote Similarity NPC24404
0.5385 Remote Similarity NPC474839
0.5385 Remote Similarity NPC313030
0.5366 Remote Similarity NPC488413
0.5366 Remote Similarity NPC488415
0.5366 Remote Similarity NPC488414
0.5366 Remote Similarity NPC488412
0.5238 Remote Similarity NPC71002
0.5238 Remote Similarity NPC249828
0.5227 Remote Similarity NPC201662
0.5217 Remote Similarity NPC611132
0.5128 Remote Similarity NPC482450

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC59506 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