Natural Product: NPC286946

Natural Product IDNPC286946
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ZNQDWWWTGJNVBY-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 71391868
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000123] Benzopyrans
        • [CHEMONTID:0003410] 1-benzopyrans
          • [CHEMONTID:0000144] Chromones

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 ZNQDWWWTGJNVBY-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O3/c1-20-17-9-5-8-15-16(19)12-14(21-18(15)17)11-10-13-6-3-2-4-7-13/h2-9,12H,10-11H2,1H3
SMILES COc1cccc2c(=O)cc(CCc3ccccc3)oc12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   280.11 Volume:   299.494
?
Van der Waals volume.
Dense:   0.935 LogP:   3.524
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.295
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.101
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   39.44
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.733 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.982 Fsp3:   0.167
MCE-18:   15.0
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.444 Fluc inhibitor:   0.337
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.473
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.6
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.496 Promiscuous compounds:   0.34

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.982 MDCK Permeability:   -4.647
Pgp-inhibitor:   0.999 Pgp-substrate:   0.025
PAMPA:   0.044
?
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):   0.002
20% Bioavailability (F20%):   0.08 30% Bioavailability (F30%):   0.15
50% Bioavailability (F50%):   0.279

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.509 MRP1:   0.786
Plasma Protein Binding (PPB):   98.393% Volume Distribution (VD):   0.433
Fu: 1.555%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.96
OATP1B3 inhibitor:   0.859 BCRP inhibitor:   0.135
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.336 CYP1A2-substrate:   0.838
CYP2C19-inhibitor:   0.79 CYP2C19-substrate:   0.399
CYP2C9-inhibitor:   0.379 CYP2C9-substrate:   0.071
CYP2D6-inhibitor:   0.189 CYP2D6-substrate:   0.917
CYP3A4-inhibitor:   0.077 CYP3A4-substrate:   0.739
CYP2B6-substrate:   0.239 CYP2C8-inhibitor:   0.829
HLM stability:   0.733
?
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):  6.99 Half-life (T1/2):  0.573

ADMET: Toxicity

hERG Blockers:  0.461 hERG Blockers (10um):  0.766
Human Hepatotoxicity (H-HT):  0.874 Drug-induced Liver Injury (DILI):  0.466
AMES Toxicity:  0.667 Rat Oral Acute Toxicity:  0.246
Maximum Recommended Daily Dose:  0.854 Skin Sensitization:  0.266
Carcinogencity:  0.678 Eye Corrosion:  0.004
Eye Irritation:  0.312 Respiratory Toxicity:  0.478
Drug-induced Neurotoxicity:  0.738 Ototoxicity:  0.457
Hematotoxicity:  0.57 Drug-induced Nephrotoxicity:  0.699
Genotoxicity:  0.954 RPMI-8226 Immunitoxicity:  0.093
A549 Cytotoxicity:  0.22 Hek293 Cytotoxicity:  0.69
BCF:   1.938
?
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:   4.327
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.229
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.971
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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
NPO12306 Gonospermum canariense Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[12880311]
NPO17039 Pharbitis nil Species Convolvulaceae Eukaryota Seeds n.a. n.a. PMID[19435339]
NPO26904 Salvia hypargeia Species Lamiaceae Eukaryota roots n.a. n.a. PMID[3236010]
NPO26082 Flindersia laevicarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26167 Strychnos cocculoides Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26137 Aplidium conicum Species Polyclinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17039 Pharbitis nil Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17039 Pharbitis nil Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26167 Strychnos cocculoides Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26974 Morella cerifera Species Myricaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17039 Pharbitis nil Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12306 Gonospermum canariense Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12277 Dendroctonus pseudotsugae Species Curculionidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24539 Veronica cupressoides Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26904 Salvia hypargeia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26728 Calycanthus chinensis Species Calycanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26137 Aplidium conicum Species Polyclinidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26729 Aster indicus Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26861 Epinetrum cordifolium n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO26928 Zanthoxylum capense Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26609 Nauclea gambir Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26784 Olea capensis Species Oleaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25795 Neurolaena macrophylla Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26082 Flindersia laevicarpa Species Rutaceae 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 NPC286946 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
0.6667 Remote Similarity NPC129443
0.6607 Remote Similarity NPC38790
0.6415 Remote Similarity NPC54243
0.6316 Remote Similarity NPC183192
0.541 Remote Similarity NPC9038
0.5246 Remote Similarity NPC7569
0.5077 Remote Similarity NPC227172
0.5065 Remote Similarity NPC478379
0.5065 Remote Similarity NPC478380

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC286946 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