Natural Product: NPC26575

Natural Product IDNPC26575
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KLXHCGFNNUQTEY-WAYWQWQTSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 6431041
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000476] Cinnamic acids and derivatives
        • [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives
          • [CHEMONTID:0000059] Coumaric acids and derivatives

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 KLXHCGFNNUQTEY-WAYWQWQTSA-N
Standard InCHI InChI=1S/C13H16O5/c1-15-10-7-9(5-6-12(14)17-3)8-11(16-2)13(10)18-4/h5-8H,1-4H3/b6-5-
SMILES COc1cc(/C=CC(=O)OC)cc(c1OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   252.1 Volume:   255.617
?
Van der Waals volume.
Dense:   0.986 LogP:   2.138
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.452
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.168
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   8.0
TPSA:   53.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.591 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.913 Fsp3:   0.308
MCE-18:   8.0
?
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:   0.258 Fluc inhibitor:   0.675
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.229
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.338
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.779 Promiscuous compounds:   0.233

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.668 MDCK Permeability:   -4.637
Pgp-inhibitor:   0.846 Pgp-substrate:   0.027
PAMPA:   0.057
?
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):   0.025
20% Bioavailability (F20%):   0.278 30% Bioavailability (F30%):   0.1
50% Bioavailability (F50%):   0.782

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.498 MRP1:   0.954
Plasma Protein Binding (PPB):   85.05% Volume Distribution (VD):   -0.208
Fu: 14.667%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.914
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.664
BSEP inhibitor:   0.983

ADMET: Metabolism

CYP1A2-inhibitor:   0.31 CYP1A2-substrate:   0.882
CYP2C19-inhibitor:   0.839 CYP2C19-substrate:   0.719
CYP2C9-inhibitor:   0.579 CYP2C9-substrate:   0.147
CYP2D6-inhibitor:   0.667 CYP2D6-substrate:   0.74
CYP3A4-inhibitor:   0.894 CYP3A4-substrate:   0.985
CYP2B6-substrate:   0.029 CYP2C8-inhibitor:   1.0
HLM stability:   0.809
?
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):  7.928 Half-life (T1/2):  1.428

ADMET: Toxicity

hERG Blockers:  0.133 hERG Blockers (10um):  0.502
Human Hepatotoxicity (H-HT):  0.431 Drug-induced Liver Injury (DILI):  0.158
AMES Toxicity:  0.462 Rat Oral Acute Toxicity:  0.177
Maximum Recommended Daily Dose:  0.302 Skin Sensitization:  0.985
Carcinogencity:  0.37 Eye Corrosion:  0.741
Eye Irritation:  0.96 Respiratory Toxicity:  0.344
Drug-induced Neurotoxicity:  0.412 Ototoxicity:  0.228
Hematotoxicity:  0.1 Drug-induced Nephrotoxicity:  0.448
Genotoxicity:  0.014 RPMI-8226 Immunitoxicity:  0.098
A549 Cytotoxicity:  0.23 Hek293 Cytotoxicity:  0.24
BCF:   0.912
?
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:   3.236
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.464
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.842
?
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
NPO5928 Streptomyces nashvillensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[1490884]
NPO9030 Couroupita guianensis Species Lecythidaceae Eukaryota n.a. n.a. n.a. PMID[37375952]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[9868158]
NPO11715 Polygonum aubertii Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2400 Streptomyces mediolani Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO5928 Streptomyces nashvillensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO868 Cephalaria gigantea Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9030 Couroupita guianensis Species Lecythidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11088 Ganoderma capense Species Ganodermataceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12667 Goniodoma pseudogoniaulax Species Coleophoridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11010 Melampyrum elatius Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3584 Oyedaea buphthalmoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11088 Ganoderma capense Species Ganodermataceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11088 Ganoderma capense Species Ganodermataceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO9030 Couroupita guianensis Species Lecythidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11010 Melampyrum elatius Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11088 Ganoderma capense Species Ganodermataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12667 Goniodoma pseudogoniaulax Species Coleophoridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3584 Oyedaea buphthalmoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11715 Polygonum aubertii Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2400 Streptomyces mediolani Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO5928 Streptomyces nashvillensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO868 Cephalaria gigantea Species Caprifoliaceae 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

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 NPC26575 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 NPC222175
0.7105 Intermediate Similarity NPC288238
0.6923 Remote Similarity NPC27352
0.6486 Remote Similarity NPC58279
0.625 Remote Similarity NPC203924
0.6 Remote Similarity NPC212643
0.5714 Remote Similarity NPC194841
0.561 Remote Similarity NPC107588
0.561 Remote Similarity NPC137537
0.5429 Remote Similarity NPC287790
0.5429 Remote Similarity NPC3672
0.5128 Remote Similarity NPC33271
0.5116 Remote Similarity NPC200014
0.5116 Remote Similarity NPC109275
0.5111 Remote Similarity NPC473809
0.5106 Remote Similarity NPC245120
0.5094 Remote Similarity NPC329640

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC26575 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