Natural Product: NPC238366

Natural Product IDNPC238366
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (3S)-5,6,7-Trimethoxy-3-(4-Methoxybenzyl)Chroman-4-One
IUPAC Name (3S)-5,6,7-trimethoxy-3-[(4-methoxyphenyl)methyl]-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2375666
PubChem CID 71713107
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002507] Homoisoflavonoids
        • [CHEMONTID:0002508] Homoisoflavans
          • [CHEMONTID:0002898] Homoisoflavanones

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 JXKHETFJYPCKAY-ZDUSSCGKSA-N
Standard InCHI InChI=1S/C20H22O6/c1-22-14-7-5-12(6-8-14)9-13-11-26-15-10-16(23-2)19(24-3)20(25-4)17(15)18(13)21/h5-8,10,13H,9,11H2,1-4H3/t13-/m0/s1
SMILES COc1ccc(cc1)C[C@H]1COc2cc(c(c(c2C1=O)OC)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   358.14 Volume:   363.093
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Van der Waals volume.
Dense:   0.986 LogP:   2.611
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.95
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.507
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   18.0
TPSA:   63.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.79 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.8 Fsp3:   0.35
MCE-18:   56.667
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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:   0.08 Fluc inhibitor:   0.419
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.246
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.391
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.307 Promiscuous compounds:   0.065

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.585 MDCK Permeability:   -4.583
Pgp-inhibitor:   0.802 Pgp-substrate:   0.015
PAMPA:   0.249
?
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):   0.0
20% Bioavailability (F20%):   0.053 30% Bioavailability (F30%):   0.002
50% Bioavailability (F50%):   0.021

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.01 MRP1:   0.935
Plasma Protein Binding (PPB):   91.755% Volume Distribution (VD):   -0.242
Fu: 7.167%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.964
OATP1B3 inhibitor:   0.931 BCRP inhibitor:   0.021
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.929 CYP1A2-substrate:   0.944
CYP2C19-inhibitor:   0.954 CYP2C19-substrate:   0.983
CYP2C9-inhibitor:   0.888 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.991
?
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):  6.266 Half-life (T1/2):  1.14

ADMET: Toxicity

hERG Blockers:  0.198 hERG Blockers (10um):  0.623
Human Hepatotoxicity (H-HT):  0.824 Drug-induced Liver Injury (DILI):  0.863
AMES Toxicity:  0.716 Rat Oral Acute Toxicity:  0.351
Maximum Recommended Daily Dose:  0.542 Skin Sensitization:  0.712
Carcinogencity:  0.887 Eye Corrosion:  0.022
Eye Irritation:  0.943 Respiratory Toxicity:  0.342
Drug-induced Neurotoxicity:  0.84 Ototoxicity:  0.393
Hematotoxicity:  0.597 Drug-induced Nephrotoxicity:  0.718
Genotoxicity:  0.727 RPMI-8226 Immunitoxicity:  0.182
A549 Cytotoxicity:  0.176 Hek293 Cytotoxicity:  0.473
BCF:   1.54
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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:   4.07
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.502
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.176
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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
NPO27354 Urginea depressa Species Hyacinthaceae Eukaryota n.a. n.a. n.a. PMID[23659371]
NPO27354 Urginea depressa Species Hyacinthaceae 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
NPT179 Cell line A2780 Homo sapiens IC50 = 1350.0 nM PMID[17253840]
NPT1383 Cell line A2058 Homo sapiens IC50 = 690.0 nM PMID[2016726]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 740.0 nM PMID[23659371]

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 NPC238366 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 NPC482972
0.7308 Intermediate Similarity NPC482974
0.717 Intermediate Similarity NPC258644
0.6364 Remote Similarity NPC606586
0.5455 Remote Similarity NPC303255
0.5439 Remote Similarity NPC129853
0.5439 Remote Similarity NPC76445
0.5179 Remote Similarity NPC170468
0.5172 Remote Similarity NPC482966
0.5161 Remote Similarity NPC482962
0.5135 Remote Similarity NPC600740

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC238366 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