Natural Product: NPC268059

Natural Product IDNPC268059
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RQIDYCZAYSCRKC-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 44257310
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 RQIDYCZAYSCRKC-UHFFFAOYSA-N
Standard InCHI InChI=1S/C22H22O6/c1-12(2)5-6-13-7-14(8-19(26-3)22(13)27-4)16-11-28-18-10-15(23)9-17(24)20(18)21(16)25/h5,7-11,23-24H,6H2,1-4H3
SMILES CC(=CCc1cc(cc(c1OC)OC)c1coc2cc(cc(c2c1=O)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   382.14 Volume:   392.412
?
Van der Waals volume.
Dense:   0.974 LogP:   3.687
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.035
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.809
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   19.0
TPSA:   89.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.636 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.724 Fsp3:   0.227
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.563 Fluc inhibitor:   0.415
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.884
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.595
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.285 Promiscuous compounds:   0.111

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.089 MDCK Permeability:   -4.793
Pgp-inhibitor:   0.294 Pgp-substrate:   0.303
PAMPA:   0.311
?
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):   0.013
20% Bioavailability (F20%):   0.969 30% Bioavailability (F30%):   0.996
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.91
Plasma Protein Binding (PPB):   95.692% Volume Distribution (VD):   0.217
Fu: 3.296%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.619
OATP1B3 inhibitor:   0.955 BCRP inhibitor:   0.999
BSEP inhibitor:   0.654

ADMET: Metabolism

CYP1A2-inhibitor:   0.953 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.955 CYP2C19-substrate:   0.683
CYP2C9-inhibitor:   0.594 CYP2C9-substrate:   0.644
CYP2D6-inhibitor:   0.98 CYP2D6-substrate:   0.985
CYP3A4-inhibitor:   0.362 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.003 CYP2C8-inhibitor:   1.0
HLM stability:   0.999
?
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):  5.42 Half-life (T1/2):  1.106

ADMET: Toxicity

hERG Blockers:  0.108 hERG Blockers (10um):  0.554
Human Hepatotoxicity (H-HT):  0.589 Drug-induced Liver Injury (DILI):  0.832
AMES Toxicity:  0.626 Rat Oral Acute Toxicity:  0.801
Maximum Recommended Daily Dose:  0.877 Skin Sensitization:  0.426
Carcinogencity:  0.714 Eye Corrosion:  0.0
Eye Irritation:  0.802 Respiratory Toxicity:  0.885
Drug-induced Neurotoxicity:  0.404 Ototoxicity:  0.372
Hematotoxicity:  0.184 Drug-induced Nephrotoxicity:  0.398
Genotoxicity:  0.987 RPMI-8226 Immunitoxicity:  0.085
A549 Cytotoxicity:  0.35 Hek293 Cytotoxicity:  0.651
BCF:   1.789
?
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:   4.453
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.814
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.258
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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 = 49400.0 nM PMID[28112509]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC = 77200.0 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 NPC268059 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 NPC233918
0.7692 Intermediate Similarity NPC128774
0.6885 Remote Similarity NPC78341
0.6567 Remote Similarity NPC238279
0.6562 Remote Similarity NPC200316
0.6471 Remote Similarity NPC213659
0.6471 Remote Similarity NPC326109
0.6462 Remote Similarity NPC481044
0.6429 Remote Similarity NPC479305
0.6406 Remote Similarity NPC239363
0.6377 Remote Similarity NPC476054
0.625 Remote Similarity NPC294409
0.625 Remote Similarity NPC490701
0.6176 Remote Similarity NPC93552
0.6164 Remote Similarity NPC52889
0.6119 Remote Similarity NPC254702
0.6 Remote Similarity NPC85131
0.6 Remote Similarity NPC232947
0.5972 Remote Similarity NPC280937
0.597 Remote Similarity NPC194653
0.5909 Remote Similarity NPC19980
0.589 Remote Similarity NPC149875
0.5821 Remote Similarity NPC309154
0.5811 Remote Similarity NPC482075
0.5797 Remote Similarity NPC104728
0.5753 Remote Similarity NPC485109
0.5714 Remote Similarity NPC167595
0.5676 Remote Similarity NPC474052
0.5645 Remote Similarity NPC193792
0.557 Remote Similarity NPC303174
0.5556 Remote Similarity NPC39426
0.5556 Remote Similarity NPC608554
0.5507 Remote Similarity NPC279668
0.5507 Remote Similarity NPC278323
0.5479 Remote Similarity NPC40942
0.5429 Remote Similarity NPC142876
0.5429 Remote Similarity NPC483637
0.5429 Remote Similarity NPC264550
0.5429 Remote Similarity NPC45291
0.5405 Remote Similarity NPC475705
0.5395 Remote Similarity NPC74178
0.5395 Remote Similarity NPC488567
0.5385 Remote Similarity NPC38065
0.5333 Remote Similarity NPC166036
0.5333 Remote Similarity NPC134287
0.527 Remote Similarity NPC219917
0.5244 Remote Similarity NPC481043
0.5195 Remote Similarity NPC107838
0.5195 Remote Similarity NPC610891
0.5176 Remote Similarity NPC324447
0.5139 Remote Similarity NPC259166
0.5135 Remote Similarity NPC482708
0.5068 Remote Similarity NPC158874
0.5065 Remote Similarity NPC253822
0.5065 Remote Similarity NPC604255
0.5063 Remote Similarity NPC474960

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC268059 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
0.5556 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