Natural Product: NPC206604

Natural Product IDNPC206604
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 LLDTYMGZAXZDDU-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5748580
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002592] 7-O-methylated flavonoids

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 LLDTYMGZAXZDDU-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H18O8/c1-23-10-7-11(20)15-13(8-10)27-17(19(26-4)16(15)22)9-5-12(21)18(25-3)14(6-9)24-2/h5-8,20-21H,1-4H3
SMILES COc1cc(c2c(c1)oc(c1cc(c(c(c1)OC)OC)O)c(c2=O)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.1 Volume:   360.741
?
Van der Waals volume.
Dense:   1.037 LogP:   2.35
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.365
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.506
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   18.0
TPSA:   107.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.702 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.515 Fsp3:   0.211
MCE-18:   20.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.217 Fluc inhibitor:   0.309
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.858
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.684
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.355 Promiscuous compounds:   0.648

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.146 MDCK Permeability:   -4.743
Pgp-inhibitor:   0.959 Pgp-substrate:   0.135
PAMPA:   0.058
?
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):   0.161
20% Bioavailability (F20%):   0.018 30% Bioavailability (F30%):   0.174
50% Bioavailability (F50%):   0.961

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.01 MRP1:   0.659
Plasma Protein Binding (PPB):   94.496% Volume Distribution (VD):   -0.535
Fu: 4.774%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.842
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.983
BSEP inhibitor:   0.978

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.745
CYP2C19-inhibitor:   0.324 CYP2C19-substrate:   0.604
CYP2C9-inhibitor:   0.897 CYP2C9-substrate:   0.01
CYP2D6-inhibitor:   0.988 CYP2D6-substrate:   0.989
CYP3A4-inhibitor:   0.007 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.958
HLM stability:   0.984
?
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):  5.0 Half-life (T1/2):  1.073

ADMET: Toxicity

hERG Blockers:  0.082 hERG Blockers (10um):  0.472
Human Hepatotoxicity (H-HT):  0.438 Drug-induced Liver Injury (DILI):  0.815
AMES Toxicity:  0.469 Rat Oral Acute Toxicity:  0.407
Maximum Recommended Daily Dose:  0.532 Skin Sensitization:  0.485
Carcinogencity:  0.735 Eye Corrosion:  0.435
Eye Irritation:  0.975 Respiratory Toxicity:  0.751
Drug-induced Neurotoxicity:  0.159 Ototoxicity:  0.161
Hematotoxicity:  0.298 Drug-induced Nephrotoxicity:  0.15
Genotoxicity:  0.46 RPMI-8226 Immunitoxicity:  0.106
A549 Cytotoxicity:  0.207 Hek293 Cytotoxicity:  0.371
BCF:   1.108
?
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:   3.522
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.608
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.822
?
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
NPO30384 Combretum quadrangulare Species Combretaceae Eukaryota n.a. n.a. n.a. PMID[10650080]
NPO30384 Combretum quadrangulare Species Combretaceae Eukaryota seeds n.a. n.a. PMID[10785422]
NPO30384 Combretum quadrangulare Species Combretaceae Eukaryota Seeds n.a. n.a. PMID[11277757]
NPO30384 Combretum quadrangulare Species Combretaceae Eukaryota n.a. leaf n.a. PMID[21265555]
NPO30384 Combretum quadrangulare Species Combretaceae Eukaryota leaves Khon Kaen, Thailand 2006-AUG PMID[21265555]
NPO32817 gardenia oudiepe Species Rubiaceae Eukaryota flowering buds and leaf bases Foret Plate, New Caledonia n.a. PMID[25659770]
NPO32817 gardenia oudiepe Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[29207340]
NPO30384 Combretum quadrangulare Species Combretaceae Eukaryota n.a. n.a. n.a. PMID[9934464]
NPO30384 Combretum quadrangulare Species Combretaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8302 Eremanthus bicolor Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2317 Euryops lateriflorus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2317 Euryops lateriflorus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8302 Eremanthus bicolor Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5333 Senecio richii Species Asteraceae 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
NPT1310 Individual protein Xanthine dehydrogenase Bos taurus IC50 = 21030.0 nM PMID[29207340]

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 NPC206604 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
0.7925 Intermediate Similarity NPC76376
0.75 Intermediate Similarity NPC177298
0.75 Intermediate Similarity NPC236769
0.7321 Intermediate Similarity NPC270620
0.7193 Intermediate Similarity NPC58382
0.7193 Intermediate Similarity NPC162351
0.7091 Intermediate Similarity NPC103904
0.7091 Intermediate Similarity NPC262094
0.7069 Intermediate Similarity NPC78326
0.7018 Intermediate Similarity NPC29841
0.6964 Remote Similarity NPC146679
0.6964 Remote Similarity NPC188871
0.6885 Remote Similarity NPC99671
0.6724 Remote Similarity NPC246204
0.661 Remote Similarity NPC55619
0.6552 Remote Similarity NPC100916
0.6441 Remote Similarity NPC200388
0.6333 Remote Similarity NPC78302
0.6333 Remote Similarity NPC235215
0.6102 Remote Similarity NPC33265
0.6034 Remote Similarity NPC607530
0.5902 Remote Similarity NPC200740
0.5806 Remote Similarity NPC25495
0.5806 Remote Similarity NPC195202
0.5806 Remote Similarity NPC223579
0.5645 Remote Similarity NPC176300
0.5645 Remote Similarity NPC153758
0.5645 Remote Similarity NPC166753
0.5574 Remote Similarity NPC48479
0.5574 Remote Similarity NPC110070
0.5574 Remote Similarity NPC87125
0.5574 Remote Similarity NPC605755
0.5574 Remote Similarity NPC610359
0.5556 Remote Similarity NPC609179
0.55 Remote Similarity NPC472438
0.5484 Remote Similarity NPC108406
0.5484 Remote Similarity NPC18772
0.5469 Remote Similarity NPC261004
0.5469 Remote Similarity NPC252933
0.5469 Remote Similarity NPC137062
0.541 Remote Similarity NPC123886
0.541 Remote Similarity NPC127447
0.541 Remote Similarity NPC152042
0.541 Remote Similarity NPC29353
0.5397 Remote Similarity NPC300943
0.5323 Remote Similarity NPC143799
0.5323 Remote Similarity NPC234133
0.5323 Remote Similarity NPC101830
0.5312 Remote Similarity NPC474520
0.5312 Remote Similarity NPC603112
0.5312 Remote Similarity NPC603596
0.5312 Remote Similarity NPC606638
0.5224 Remote Similarity NPC76482
0.5195 Remote Similarity NPC611303
0.5156 Remote Similarity NPC115798
0.5156 Remote Similarity NPC82325
0.5156 Remote Similarity NPC178854
0.5156 Remote Similarity NPC328119
0.5156 Remote Similarity NPC604677
0.5156 Remote Similarity NPC605582
0.5132 Remote Similarity NPC84362
0.5079 Remote Similarity NPC59951
0.5079 Remote Similarity NPC32557
0.5077 Remote Similarity NPC18607
0.5077 Remote Similarity NPC605494

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC206604 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