Natural Product: NPC233918

Natural Product IDNPC233918
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KWZLIQOQDYHGPK-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 15391015
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002606] 4'-O-methylated isoflavonoids
            • [CHEMONTID:0002687] 4'-O-methylisoflavones

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 KWZLIQOQDYHGPK-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H20O5/c1-12(2)4-5-14-8-13(6-7-18(14)25-3)16-11-26-19-10-15(22)9-17(23)20(19)21(16)24/h4,6-11,22-23H,5H2,1-3H3
SMILES CC(=CCc1cc(ccc1OC)c1coc2cc(cc(c2c1=O)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   352.13 Volume:   366.326
?
Van der Waals volume.
Dense:   0.961 LogP:   4.003
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.225
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.777
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   79.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.681 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.613 Fsp3:   0.19
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.854 Fluc inhibitor:   0.805
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.913
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.651
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.313 Promiscuous compounds:   0.097

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.003 MDCK Permeability:   -4.77
Pgp-inhibitor:   0.276 Pgp-substrate:   0.157
PAMPA:   0.288
?
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):   0.119
20% Bioavailability (F20%):   0.992 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.526
Plasma Protein Binding (PPB):   96.135% Volume Distribution (VD):   0.303
Fu: 3.198%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.604
OATP1B3 inhibitor:   0.888 BCRP inhibitor:   0.999
BSEP inhibitor:   0.476

ADMET: Metabolism

CYP1A2-inhibitor:   0.945 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.614 CYP2C19-substrate:   0.605
CYP2C9-inhibitor:   0.347 CYP2C9-substrate:   0.997
CYP2D6-inhibitor:   0.971 CYP2D6-substrate:   0.945
CYP3A4-inhibitor:   0.007 CYP3A4-substrate:   0.998
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.997
?
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):  5.953 Half-life (T1/2):  0.943

ADMET: Toxicity

hERG Blockers:  0.177 hERG Blockers (10um):  0.581
Human Hepatotoxicity (H-HT):  0.595 Drug-induced Liver Injury (DILI):  0.861
AMES Toxicity:  0.698 Rat Oral Acute Toxicity:  0.76
Maximum Recommended Daily Dose:  0.857 Skin Sensitization:  0.523
Carcinogencity:  0.723 Eye Corrosion:  0.001
Eye Irritation:  0.862 Respiratory Toxicity:  0.888
Drug-induced Neurotoxicity:  0.379 Ototoxicity:  0.37
Hematotoxicity:  0.177 Drug-induced Nephrotoxicity:  0.411
Genotoxicity:  0.976 RPMI-8226 Immunitoxicity:  0.081
A549 Cytotoxicity:  0.359 Hek293 Cytotoxicity:  0.665
BCF:   1.821
?
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:   4.635
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.941
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.437
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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
NPO40124 Erythrina schliebenii Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[28112509]
NPO40124 Erythrina schliebenii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT82 Cell line MDA-MB-231 Homo sapiens EC50 = 27900.0 nM PMID[28112509]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC = 36900.0 nM PMID[28112509]

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 NPC233918 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
0.7812 Intermediate Similarity NPC268059
0.7692 Intermediate Similarity NPC128774
0.7576 Intermediate Similarity NPC149875
0.7049 Intermediate Similarity NPC294409
0.7049 Intermediate Similarity NPC490701
0.697 Remote Similarity NPC213659
0.697 Remote Similarity NPC326109
0.6825 Remote Similarity NPC200316
0.6719 Remote Similarity NPC194653
0.6667 Remote Similarity NPC479305
0.6613 Remote Similarity NPC78341
0.6567 Remote Similarity NPC238279
0.6479 Remote Similarity NPC107838
0.6232 Remote Similarity NPC85131
0.6232 Remote Similarity NPC232947
0.6176 Remote Similarity NPC93552
0.6143 Remote Similarity NPC40942
0.6119 Remote Similarity NPC254702
0.6061 Remote Similarity NPC309154
0.6029 Remote Similarity NPC104728
0.597 Remote Similarity NPC279668
0.597 Remote Similarity NPC278323
0.597 Remote Similarity NPC481044
0.5946 Remote Similarity NPC52889
0.5909 Remote Similarity NPC239363
0.5882 Remote Similarity NPC142876
0.5833 Remote Similarity NPC475705
0.5811 Remote Similarity NPC231763
0.5811 Remote Similarity NPC482075
0.5806 Remote Similarity NPC39426
0.5806 Remote Similarity NPC608554
0.5783 Remote Similarity NPC121647
0.5753 Remote Similarity NPC485109
0.5694 Remote Similarity NPC219917
0.5676 Remote Similarity NPC474052
0.5676 Remote Similarity NPC604255
0.5672 Remote Similarity NPC19980
0.5652 Remote Similarity NPC483637
0.5652 Remote Similarity NPC264550
0.5645 Remote Similarity NPC193792
0.5625 Remote Similarity NPC302762
0.5625 Remote Similarity NPC38065
0.557 Remote Similarity NPC303174
0.5542 Remote Similarity NPC324447
0.5541 Remote Similarity NPC280937
0.5429 Remote Similarity NPC45291
0.5352 Remote Similarity NPC259166
0.5342 Remote Similarity NPC482708
0.5333 Remote Similarity NPC166036
0.5278 Remote Similarity NPC167595
0.527 Remote Similarity NPC249824
0.527 Remote Similarity NPC48624
0.527 Remote Similarity NPC133400
0.5263 Remote Similarity NPC26051
0.5263 Remote Similarity NPC476178
0.5256 Remote Similarity NPC474960
0.5256 Remote Similarity NPC7989
0.5195 Remote Similarity NPC74178
0.5195 Remote Similarity NPC303197
0.5195 Remote Similarity NPC610891
0.5152 Remote Similarity NPC87545
0.5147 Remote Similarity NPC116632
0.5147 Remote Similarity NPC35763
0.5139 Remote Similarity NPC144118
0.5135 Remote Similarity NPC215311
0.5132 Remote Similarity NPC134287
0.5068 Remote Similarity NPC158874
0.5068 Remote Similarity NPC20472
0.5068 Remote Similarity NPC241904
0.5068 Remote Similarity NPC606446
0.5067 Remote Similarity NPC80962
0.5065 Remote Similarity NPC269285
0.5065 Remote Similarity NPC253822
0.5065 Remote Similarity NPC488570
0.5062 Remote Similarity NPC156457
0.506 Remote Similarity NPC488441

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC233918 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
0.5806 Remote Similarity NPD1510 Phase 2

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