Natural Product: NPC236428

Natural Product IDNPC236428
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 SZMSRIIZCHESKM-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5493671
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000123] Benzopyrans
        • [CHEMONTID:0003410] 1-benzopyrans
          • [CHEMONTID:0002817] Dibenzopyrans
            • [CHEMONTID:0000200] Xanthenes
              • [CHEMONTID:0000204] Xanthones
                • [CHEMONTID:0003519] 8-prenylated xanthones

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 SZMSRIIZCHESKM-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O5/c1-9(2)3-4-10-5-6-12(20)18-15(10)17(22)16-13(21)7-11(19)8-14(16)23-18/h3,5-8,19-21H,4H2,1-2H3
SMILES CC(=CCc1ccc(c2c1c(=O)c1c(cc(cc1o2)O)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   312.1 Volume:   317.074
?
Van der Waals volume.
Dense:   0.984 LogP:   3.216
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.869
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.756
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   90.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.497 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.871 Fsp3:   0.167
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.788 Fluc inhibitor:   0.545
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.956
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.678
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.321 Promiscuous compounds:   0.104

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.077 MDCK Permeability:   -4.819
Pgp-inhibitor:   0.102 Pgp-substrate:   0.637
PAMPA:   0.693
?
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):   0.169
20% Bioavailability (F20%):   0.927 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.881
Plasma Protein Binding (PPB):   93.886% Volume Distribution (VD):   0.475
Fu: 6.324%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.527
OATP1B3 inhibitor:   0.806 BCRP inhibitor:   0.99
BSEP inhibitor:   0.317

ADMET: Metabolism

CYP1A2-inhibitor:   0.313 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.652 CYP2C19-substrate:   0.981
CYP2C9-inhibitor:   0.026 CYP2C9-substrate:   0.931
CYP2D6-inhibitor:   0.981 CYP2D6-substrate:   0.949
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.989
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  6.403 Half-life (T1/2):  1.163

ADMET: Toxicity

hERG Blockers:  0.06 hERG Blockers (10um):  0.507
Human Hepatotoxicity (H-HT):  0.433 Drug-induced Liver Injury (DILI):  0.833
AMES Toxicity:  0.734 Rat Oral Acute Toxicity:  0.625
Maximum Recommended Daily Dose:  0.712 Skin Sensitization:  0.916
Carcinogencity:  0.769 Eye Corrosion:  0.11
Eye Irritation:  0.98 Respiratory Toxicity:  0.807
Drug-induced Neurotoxicity:  0.037 Ototoxicity:  0.134
Hematotoxicity:  0.067 Drug-induced Nephrotoxicity:  0.059
Genotoxicity:  0.965 RPMI-8226 Immunitoxicity:  0.037
A549 Cytotoxicity:  0.259 Hek293 Cytotoxicity:  0.567
BCF:   1.711
?
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:   4.452
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.667
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.186
?
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
NPO19755 Artemisia anomala Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[20000780]
NPO7336 Senecio brasiliensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18013 Sceletium subvelutinum n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO1755 Pinus heldreichii Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18412 Lobophytum microlobulatum Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16291 Leptochloa digitata Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19563 Gyrophora hyperborea n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO11057 Artocarpus integra Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17885 Eupatorium sachalinense Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19755 Artemisia anomala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18911 Piper umbellatum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17885 Eupatorium sachalinense Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11057 Artocarpus integra Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7336 Senecio brasiliensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19755 Artemisia anomala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18911 Piper umbellatum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11057 Artocarpus integra Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19755 Artemisia anomala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7336 Senecio brasiliensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18911 Piper umbellatum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17885 Eupatorium sachalinense Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19755 Artemisia anomala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16291 Leptochloa digitata Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19563 Gyrophora hyperborea n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO18911 Piper umbellatum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18412 Lobophytum microlobulatum Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7336 Senecio brasiliensis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18013 Sceletium subvelutinum n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO1755 Pinus heldreichii Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11057 Artocarpus integra Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19755 Artemisia anomala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17885 Eupatorium sachalinense 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

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 NPC236428 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
0.7119 Intermediate Similarity NPC274730
0.6129 Remote Similarity NPC89474
0.5942 Remote Similarity NPC136674
0.5758 Remote Similarity NPC241904
0.5439 Remote Similarity NPC61620
0.5246 Remote Similarity NPC151473
0.5224 Remote Similarity NPC100123
0.5167 Remote Similarity NPC272721
0.5085 Remote Similarity NPC275734
0.5072 Remote Similarity NPC190046

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC236428 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