Natural Product: NPC199204

Natural Product IDNPC199204
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Phebalosin
IUPAC Name 7-methoxy-8-[(2R,3R)-3-prop-1-en-2-yloxiran-2-yl]chromen-2-one
Synonyms Phebalosin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL486409
PubChem CID 188300
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives

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 YTDNHMHONBWCBV-UKRRQHHQSA-N
Standard InCHI InChI=1S/C15H14O4/c1-8(2)13-15(19-13)12-10(17-3)6-4-9-5-7-11(16)18-14(9)12/h4-7,13,15H,1H2,2-3H3/t13-,15-/m1/s1
SMILES COc1ccc2c(c1[C@H]1O[C@@H]1C(=C)C)oc(=O)cc2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   258.09 Volume:   261.669
?
Van der Waals volume.
Dense:   0.986 LogP:   1.999
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.329
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.528
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   16.0
TPSA:   51.97
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.482 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.469 Fsp3:   0.267
MCE-18:   54.579
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.596 Fluc inhibitor:   0.086
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.944
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.424
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.523 Promiscuous compounds:   0.292

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.8 MDCK Permeability:   -4.449
Pgp-inhibitor:   0.014 Pgp-substrate:   0.0
PAMPA:   0.079
?
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%):   0.425 30% Bioavailability (F30%):   0.687
50% Bioavailability (F50%):   0.427

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.994
Plasma Protein Binding (PPB):   94.622% Volume Distribution (VD):   0.126
Fu: 4.637%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.001
BSEP inhibitor:   0.972

ADMET: Metabolism

CYP1A2-inhibitor:   0.008 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.986 CYP2C19-substrate:   0.228
CYP2C9-inhibitor:   0.276 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.034 CYP2D6-substrate:   0.712
CYP3A4-inhibitor:   0.676 CYP3A4-substrate:   0.986
CYP2B6-substrate:   0.883 CYP2C8-inhibitor:   0.995
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):  10.08 Half-life (T1/2):  0.958

ADMET: Toxicity

hERG Blockers:  0.095 hERG Blockers (10um):  0.315
Human Hepatotoxicity (H-HT):  0.686 Drug-induced Liver Injury (DILI):  0.91
AMES Toxicity:  0.838 Rat Oral Acute Toxicity:  0.499
Maximum Recommended Daily Dose:  0.581 Skin Sensitization:  0.597
Carcinogencity:  0.735 Eye Corrosion:  0.551
Eye Irritation:  0.991 Respiratory Toxicity:  0.564
Drug-induced Neurotoxicity:  0.55 Ototoxicity:  0.204
Hematotoxicity:  0.466 Drug-induced Nephrotoxicity:  0.329
Genotoxicity:  0.948 RPMI-8226 Immunitoxicity:  0.133
A549 Cytotoxicity:  0.087 Hek293 Cytotoxicity:  0.295
BCF:   1.526
?
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:   4.113
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.891
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.282
?
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
NPO5744 Galipea panamensis Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[20423106]
NPO26959 Micromelum minutum Species Rutaceae Eukaryota Barks n.a. n.a. PMID[3754570]
NPO5744 Galipea panamensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26959 Micromelum minutum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26959 Micromelum minutum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5744 Galipea panamensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26959 Micromelum minutum 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
NPT466 Cell line U-937 Homo sapiens CC50 = 20.7 ug.mL-1 PMID[21135175]
NPT141 Organism Agrobacterium tumefaciens Agrobacterium tumefaciens Activity = -70.0 % PMID[24601655]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. ED50 > 20.0 ug ml-1 PMID[3754570]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. ED50 = 27.0 ug ml-1 PMID[3754570]

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
- Artemia LC50 = 47.0 ppm PMID[21784631]

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 NPC199204 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
0.7679 Intermediate Similarity NPC469675
0.7049 Intermediate Similarity NPC484110
0.6441 Remote Similarity NPC26954
0.6441 Remote Similarity NPC38099
0.6271 Remote Similarity NPC167111
0.6271 Remote Similarity NPC318400
0.6094 Remote Similarity NPC195343
0.6094 Remote Similarity NPC267412
0.6094 Remote Similarity NPC74655
0.6032 Remote Similarity NPC166672
0.6032 Remote Similarity NPC484113
0.6 Remote Similarity NPC84894
0.6 Remote Similarity NPC18804
0.6 Remote Similarity NPC319859
0.6 Remote Similarity NPC164269
0.6 Remote Similarity NPC198381
0.6 Remote Similarity NPC287182
0.6 Remote Similarity NPC127888
0.5932 Remote Similarity NPC168710
0.5893 Remote Similarity NPC80170
0.5873 Remote Similarity NPC476457
0.5846 Remote Similarity NPC149320
0.5846 Remote Similarity NPC160727
0.5846 Remote Similarity NPC177281
0.5846 Remote Similarity NPC471910
0.5789 Remote Similarity NPC50896
0.5789 Remote Similarity NPC326600
0.5789 Remote Similarity NPC122259
0.5781 Remote Similarity NPC86892
0.5781 Remote Similarity NPC471909
0.5758 Remote Similarity NPC128529
0.5758 Remote Similarity NPC307412
0.5758 Remote Similarity NPC296624
0.5758 Remote Similarity NPC55615
0.5758 Remote Similarity NPC606124
0.5735 Remote Similarity NPC471625
0.5714 Remote Similarity NPC175159
0.5652 Remote Similarity NPC100986
0.5614 Remote Similarity NPC96286
0.5574 Remote Similarity NPC153818
0.5574 Remote Similarity NPC232246
0.5538 Remote Similarity NPC129572
0.5522 Remote Similarity NPC476455
0.5517 Remote Similarity NPC610664
0.5493 Remote Similarity NPC471630
0.5424 Remote Similarity NPC62366
0.541 Remote Similarity NPC605506
0.5352 Remote Similarity NPC283019
0.5345 Remote Similarity NPC55147
0.5345 Remote Similarity NPC472516
0.5345 Remote Similarity NPC271600
0.5254 Remote Similarity NPC229916
0.5224 Remote Similarity NPC195357
0.5224 Remote Similarity NPC152771
0.5167 Remote Similarity NPC185066
0.5152 Remote Similarity NPC260265
0.5147 Remote Similarity NPC312881

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC199204 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