Natural Product: NPC153149

Natural Product IDNPC153149
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ZDLZDPFUIWTENT-RKQHYHRCSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10313649
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates
          • [CHEMONTID:0002105] Glycosyl compounds
            • [CHEMONTID:0004165] Phenolic glycosides

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 ZDLZDPFUIWTENT-RKQHYHRCSA-N
Standard InCHI InChI=1S/C14H20O8/c1-19-8-4-3-7(5-9(8)20-2)21-14-13(18)12(17)11(16)10(6-15)22-14/h3-5,10-18H,6H2,1-2H3/t10-,11-,12+,13-,14-/m1/s1
SMILES COc1ccc(cc1OC)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.12 Volume:   296.0
?
Van der Waals volume.
Dense:   1.068 LogP:   -0.416
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.004
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.386
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   12.0
TPSA:   117.84
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.54 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.277 Fsp3:   0.571
MCE-18:   48.364
?
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:   0.5 Fluc inhibitor:   0.003
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.199
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.064
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.246 Promiscuous compounds:   0.211

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.511 MDCK Permeability:   -4.873
Pgp-inhibitor:   0.002 Pgp-substrate:   0.21
PAMPA:   0.752
?
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):   0.866
20% Bioavailability (F20%):   0.066 30% Bioavailability (F30%):   0.693
50% Bioavailability (F50%):   0.831

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.044 MRP1:   0.171
Plasma Protein Binding (PPB):   57.627% Volume Distribution (VD):   -0.225
Fu: 39.096%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.275
BSEP inhibitor:   0.015

ADMET: Metabolism

CYP1A2-inhibitor:   0.107 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.138 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.004 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.003 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   0.027 CYP3A4-substrate:   0.004
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.283
HLM stability:   0.012
?
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):  2.418 Half-life (T1/2):  3.994

ADMET: Toxicity

hERG Blockers:  0.042 hERG Blockers (10um):  0.139
Human Hepatotoxicity (H-HT):  0.686 Drug-induced Liver Injury (DILI):  0.861
AMES Toxicity:  0.88 Rat Oral Acute Toxicity:  0.027
Maximum Recommended Daily Dose:  0.011 Skin Sensitization:  0.988
Carcinogencity:  0.382 Eye Corrosion:  0.002
Eye Irritation:  0.542 Respiratory Toxicity:  0.034
Drug-induced Neurotoxicity:  0.057 Ototoxicity:  0.878
Hematotoxicity:  0.466 Drug-induced Nephrotoxicity:  0.765
Genotoxicity:  0.091 RPMI-8226 Immunitoxicity:  0.096
A549 Cytotoxicity:  0.116 Hek293 Cytotoxicity:  0.1
BCF:   0.29
?
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:   2.491
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.942
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.125
?
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
NPO22437 Eurya japonica Species Pentaphylacaceae Eukaryota n.a. n.a. n.a. PMID[23540981]
NPO22437 Eurya japonica Species Pentaphylacaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22437 Eurya japonica Species Pentaphylacaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22437 Eurya japonica Species Pentaphylacaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22437 Eurya japonica Species Pentaphylacaceae 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
NPT844 Organism Trypanosoma brucei rhodesiense Trypanosoma brucei rhodesiense Activity = 8.9 % PMID[34965114]
NPT843 Organism Trypanosoma evansi Trypanosoma evansi Activity = 0.0 % PMID[34965114]
NPT844 Organism Trypanosoma brucei rhodesiense Trypanosoma brucei rhodesiense Activity = 0.0 % PMID[34965114]
NPT2229 Organism Trypanosoma brucei gambiense Trypanosoma brucei gambiense Activity = 0.0 % PMID[34965114]
NPT1 Others Radical scavenging activity n.a. ED50 > 100.0 uM PMID[23540981]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei Activity = 0.0 % PMID[34965114]

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 NPC153149 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
0.9268 High Similarity NPC25817
0.7674 Intermediate Similarity NPC276195
0.75 Intermediate Similarity NPC217854
0.7308 Intermediate Similarity NPC247146
0.6744 Remote Similarity NPC228907
0.6735 Remote Similarity NPC221090
0.6735 Remote Similarity NPC145900
0.6596 Remote Similarity NPC192810
0.6522 Remote Similarity NPC142319
0.617 Remote Similarity NPC212729
0.617 Remote Similarity NPC604498
0.6122 Remote Similarity NPC152722
0.6042 Remote Similarity NPC269242
0.6038 Remote Similarity NPC218685
0.6 Remote Similarity NPC299144
0.6 Remote Similarity NPC609376
0.5962 Remote Similarity NPC166040
0.5926 Remote Similarity NPC479028
0.5926 Remote Similarity NPC23084
0.5926 Remote Similarity NPC479031
0.5918 Remote Similarity NPC294470
0.5893 Remote Similarity NPC104167
0.5769 Remote Similarity NPC69513
0.5714 Remote Similarity NPC479029
0.5686 Remote Similarity NPC60589
0.5686 Remote Similarity NPC469708
0.5686 Remote Similarity NPC604439
0.566 Remote Similarity NPC48863
0.566 Remote Similarity NPC95292
0.566 Remote Similarity NPC251981
0.566 Remote Similarity NPC13745
0.5636 Remote Similarity NPC472024
0.5636 Remote Similarity NPC270849
0.5636 Remote Similarity NPC604356
0.5577 Remote Similarity NPC200092
0.5556 Remote Similarity NPC215833
0.5556 Remote Similarity NPC108674
0.5536 Remote Similarity NPC26653
0.5536 Remote Similarity NPC80600
0.5536 Remote Similarity NPC210478
0.55 Remote Similarity NPC479030
0.549 Remote Similarity NPC9248
0.5472 Remote Similarity NPC80098
0.5455 Remote Similarity NPC49074
0.5439 Remote Similarity NPC248355
0.5439 Remote Similarity NPC473044
0.54 Remote Similarity NPC484157
0.537 Remote Similarity NPC214454
0.5357 Remote Similarity NPC162093
0.5345 Remote Similarity NPC55040
0.5323 Remote Similarity NPC472859
0.5283 Remote Similarity NPC12308
0.5283 Remote Similarity NPC226712
0.5283 Remote Similarity NPC608788
0.5273 Remote Similarity NPC310661
0.5273 Remote Similarity NPC9912
0.5263 Remote Similarity NPC214910
0.5254 Remote Similarity NPC302378
0.5254 Remote Similarity NPC473045
0.5254 Remote Similarity NPC232673
0.5254 Remote Similarity NPC112766
0.5246 Remote Similarity NPC37468
0.5246 Remote Similarity NPC37074
0.5246 Remote Similarity NPC246947
0.5238 Remote Similarity NPC99233
0.5167 Remote Similarity NPC601455
0.5161 Remote Similarity NPC287780
0.5161 Remote Similarity NPC60982
0.5161 Remote Similarity NPC604892
0.5091 Remote Similarity NPC166168
0.5088 Remote Similarity NPC251102
0.5088 Remote Similarity NPC83975
0.5088 Remote Similarity NPC210298
0.5088 Remote Similarity NPC606892
0.5085 Remote Similarity NPC95392
0.5085 Remote Similarity NPC84013
0.5085 Remote Similarity NPC55715
0.5085 Remote Similarity NPC35877
0.5085 Remote Similarity NPC189589
0.5085 Remote Similarity NPC25292
0.5082 Remote Similarity NPC294166
0.5082 Remote Similarity NPC276753
0.5082 Remote Similarity NPC78809
0.5082 Remote Similarity NPC205796
0.5082 Remote Similarity NPC115022

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC153149 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
0.5283 Remote Similarity NPD1091 Pre-clinical

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