Natural Product: NPC297364

Natural Product IDNPC297364
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ASAOSMVQLGTAQO-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 12085264
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002591] 6-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 ASAOSMVQLGTAQO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O7/c1-22-9-5-3-8(4-6-9)11-7-10(18)12-13(19)17(23-2)15(21)14(20)16(12)24-11/h3-7,19-21H,1-2H3
SMILES COc1ccc(cc1)c1cc(=O)c2c(c(c(c(c2o1)O)O)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   330.07 Volume:   317.359
?
Van der Waals volume.
Dense:   1.04 LogP:   2.551
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.602
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.453
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   109.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.5 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.467 Fsp3:   0.118
MCE-18:   19.0
?
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:   1
Colloidal aggregators:   0.642 Fluc inhibitor:   0.94
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.803
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.625
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.437 Promiscuous compounds:   0.934

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.131 MDCK Permeability:   -4.804
Pgp-inhibitor:   0.562 Pgp-substrate:   0.072
PAMPA:   0.215
?
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):   0.204
20% Bioavailability (F20%):   0.343 30% Bioavailability (F30%):   0.651
50% Bioavailability (F50%):   0.947

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.021 MRP1:   0.942
Plasma Protein Binding (PPB):   96.886% Volume Distribution (VD):   -0.574
Fu: 2.237%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.936
OATP1B3 inhibitor:   0.991 BCRP inhibitor:   0.913
BSEP inhibitor:   0.511

ADMET: Metabolism

CYP1A2-inhibitor:   0.428 CYP1A2-substrate:   0.496
CYP2C19-inhibitor:   0.003 CYP2C19-substrate:   0.127
CYP2C9-inhibitor:   0.983 CYP2C9-substrate:   0.451
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.978
CYP3A4-inhibitor:   0.007 CYP3A4-substrate:   0.427
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.718
?
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):  7.441 Half-life (T1/2):  1.182

ADMET: Toxicity

hERG Blockers:  0.117 hERG Blockers (10um):  0.457
Human Hepatotoxicity (H-HT):  0.435 Drug-induced Liver Injury (DILI):  0.923
AMES Toxicity:  0.612 Rat Oral Acute Toxicity:  0.347
Maximum Recommended Daily Dose:  0.493 Skin Sensitization:  0.686
Carcinogencity:  0.693 Eye Corrosion:  0.195
Eye Irritation:  0.976 Respiratory Toxicity:  0.599
Drug-induced Neurotoxicity:  0.071 Ototoxicity:  0.217
Hematotoxicity:  0.212 Drug-induced Nephrotoxicity:  0.116
Genotoxicity:  0.519 RPMI-8226 Immunitoxicity:  0.048
A549 Cytotoxicity:  0.309 Hek293 Cytotoxicity:  0.308
BCF:   1.016
?
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:   3.77
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.686
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.246
?
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
NPO25890 Herba cirsii japonici n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO23795 Herba seu radix cirsii japonici n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO19689 Radix cirsii japonici Species Lymnaeidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25890 Herba cirsii japonici n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO19689 Radix cirsii japonici Species Lymnaeidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23795 Herba seu radix cirsii japonici n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]

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 NPC297364 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
0.7308 Intermediate Similarity NPC604462
0.6792 Remote Similarity NPC274327
0.6792 Remote Similarity NPC156222
0.6364 Remote Similarity NPC176775
0.6364 Remote Similarity NPC57030
0.6364 Remote Similarity NPC145379
0.6182 Remote Similarity NPC52611
0.6182 Remote Similarity NPC29353
0.6182 Remote Similarity NPC600177
0.6071 Remote Similarity NPC184136
0.6071 Remote Similarity NPC231772
0.5965 Remote Similarity NPC603662
0.5714 Remote Similarity NPC607196
0.569 Remote Similarity NPC163780
0.569 Remote Similarity NPC256283
0.5667 Remote Similarity NPC610914
0.5593 Remote Similarity NPC146165
0.5517 Remote Similarity NPC22519
0.5517 Remote Similarity NPC266597
0.5517 Remote Similarity NPC604085
0.5439 Remote Similarity NPC293183
0.5439 Remote Similarity NPC602963
0.5385 Remote Similarity NPC470402
0.5345 Remote Similarity NPC241498
0.5345 Remote Similarity NPC275836
0.5345 Remote Similarity NPC187498
0.5345 Remote Similarity NPC609958
0.5333 Remote Similarity NPC183597
0.5333 Remote Similarity NPC212678
0.5333 Remote Similarity NPC255350
0.5246 Remote Similarity NPC160951
0.5246 Remote Similarity NPC196439
0.5246 Remote Similarity NPC223579
0.5179 Remote Similarity NPC40818
0.5179 Remote Similarity NPC604293
0.5091 Remote Similarity NPC216318
0.5088 Remote Similarity NPC101294
0.5088 Remote Similarity NPC2771
0.5085 Remote Similarity NPC203891
0.5085 Remote Similarity NPC71334
0.5085 Remote Similarity NPC44079
0.5085 Remote Similarity NPC275722
0.5085 Remote Similarity NPC127447
0.5085 Remote Similarity NPC239128
0.5082 Remote Similarity NPC69394
0.5082 Remote Similarity NPC280339
0.5079 Remote Similarity NPC295036

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC297364 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
0.5333 Remote Similarity NPD2801 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