Natural Product: NPC266597

Natural Product IDNPC266597
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Pratol
IUPAC Name 7-hydroxy-2-(4-methoxyphenyl)chromen-4-one
Synonyms NSC-123414
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL16751
PubChem CID 5320693
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002596] 4'-O-methylated flavonoids

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 SQVXWIUVAILQRH-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O4/c1-19-12-5-2-10(3-6-12)15-9-14(18)13-7-4-11(17)8-16(13)20-15/h2-9,17H,1H3
SMILES COc1ccc(cc1)c1cc(=O)c2c(o1)cc(cc2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   268.07 Volume:   273.692
?
Van der Waals volume.
Dense:   0.979 LogP:   2.753
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.951
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.675
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   59.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.775 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.923 Fsp3:   0.062
MCE-18:   16.0
?
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:   0.523 Fluc inhibitor:   0.999
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.992
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.82
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.778 Promiscuous compounds:   0.487

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.726 MDCK Permeability:   -4.684
Pgp-inhibitor:   0.12 Pgp-substrate:   0.578
PAMPA:   0.231
?
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):   0.113
20% Bioavailability (F20%):   0.68 30% Bioavailability (F30%):   0.84
50% Bioavailability (F50%):   0.962

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.017 MRP1:   0.76
Plasma Protein Binding (PPB):   96.45% Volume Distribution (VD):   -0.277
Fu: 3.463%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.784
OATP1B3 inhibitor:   0.986 BCRP inhibitor:   0.921
BSEP inhibitor:   0.912

ADMET: Metabolism

CYP1A2-inhibitor:   0.994 CYP1A2-substrate:   0.696
CYP2C19-inhibitor:   0.29 CYP2C19-substrate:   0.029
CYP2C9-inhibitor:   0.996 CYP2C9-substrate:   0.824
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.013 CYP3A4-substrate:   0.152
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   1.0
HLM stability:   0.892
?
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):  5.775 Half-life (T1/2):  1.093

ADMET: Toxicity

hERG Blockers:  0.154 hERG Blockers (10um):  0.452
Human Hepatotoxicity (H-HT):  0.41 Drug-induced Liver Injury (DILI):  0.861
AMES Toxicity:  0.676 Rat Oral Acute Toxicity:  0.392
Maximum Recommended Daily Dose:  0.825 Skin Sensitization:  0.285
Carcinogencity:  0.861 Eye Corrosion:  0.477
Eye Irritation:  0.993 Respiratory Toxicity:  0.778
Drug-induced Neurotoxicity:  0.22 Ototoxicity:  0.077
Hematotoxicity:  0.171 Drug-induced Nephrotoxicity:  0.1
Genotoxicity:  0.978 RPMI-8226 Immunitoxicity:  0.063
A549 Cytotoxicity:  0.146 Hek293 Cytotoxicity:  0.696
BCF:   1.262
?
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:   3.995
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.792
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.42
?
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
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0031-9422(00)94679-X]
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[30199256]
NPO6792 Hedysarum polybotrys Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25433 Rhizoma fagopyri cymosi n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7960 Cicer arietinum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7960 Cicer arietinum Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO7960 Cicer arietinum Species Fabaceae Eukaryota n.a. n.a. Database[FooDB]
NPO7960 Cicer arietinum Species Fabaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO27772 Flos inulae Species Lycaenidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7960 Cicer arietinum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17782.1 Inula britannica var. chinensis Varieties Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7960 Cicer arietinum Species Fabaceae Eukaryota Seeds n.a. Database[Phenol-Explorer]
NPO7960 Cicer arietinum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17782.1 Inula britannica var. chinensis Varieties Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27772 Flos inulae Species Lycaenidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25433 Rhizoma fagopyri cymosi n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7960 Cicer arietinum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22104 Trifolium pratense Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO6792 Hedysarum polybotrys Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO1211 Tachypleus tridentatus Species Limulidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6792 Hedysarum polybotrys Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22104 Trifolium pratense Species Fabaceae 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
NPT213 Individual protein Cytochrome P450 2C19 Homo sapiens Potency = 3162.3 nM PubChem BioAssay data set
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens Potency = 7943.3 nM PubChem BioAssay data set
NPT212 Individual protein Cytochrome P450 2C9 Homo sapiens Potency = 3981.1 nM PubChem BioAssay data set
NPT199 Individual protein DNA polymerase kappa Homo sapiens Potency n.a. 37685.8 nM PubChem BioAssay data set
NPT156 Individual protein Sphingomyelin phosphodiesterase Homo sapiens Potency n.a. 31622.8 nM PubChem BioAssay data set
NPT157 Individual protein Breast cancer type 1 susceptibility protein Homo sapiens Potency n.a. 10000.0 nM PubChem BioAssay data set
NPT11 Individual protein Guanine nucleotide-binding protein G(s), subunit alpha Homo sapiens Potency n.a. 50118.7 nM PubChem BioAssay data set
NPT1417 Individual protein Transcriptional regulator ERG Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT1380 Individual protein Avian myoblastosis virus polyprotein II Avian myeloblastosis virus Inhibition = 13.6 % DOI[10.1007/s00044-011-9570-z]
NPT2562 Individual protein Poly [ADP-ribose] polymerase-1 Homo sapiens IC50 > 100000.0 nM PMID[23574272]
NPT2563 Individual protein Tankyrase-2 Homo sapiens IC50 = 457.09 nM PMID[23574272]
NPT2563 Individual protein Tankyrase-2 Homo sapiens IC50 = 450.0 nM PMID[23574272]
NPT3117 Individual protein Glutaminyl-peptide cyclotransferase Homo sapiens Inhibition = 75.2 % PMID[27061673]
NPT2749 Individual protein Acetylcholinesterase Rattus norvegicus IC50 = 35.0 nM PMID[29089261]
NPT791 Individual protein Cruzipain Trypanosoma cruzi Potency = 39810.7 nM PubChem BioAssay data set
NPT888 Individual protein 78 kDa glucose-regulated protein Homo sapiens Potency n.a. 3981.1 nM PubChem BioAssay data set
NPT67 Individual protein Cholinesterase Equus caballus Inhibition = 6.46 % PMID[23062825]
NPT588 Individual protein Tankyrase-1 Homo sapiens IC50 = 562.34 nM PMID[23574272]
NPT588 Individual protein Tankyrase-1 Homo sapiens IC50 = 560.0 nM PMID[23574272]
NPT755 Individual protein Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 Homo sapiens Potency n.a. 28183.8 nM PubChem BioAssay data set
NPT66 Individual protein Acetylcholinesterase Electrophorus electricus Inhibition = 30.64 % PMID[23062825]
NPT581 Individual protein Cyclooxygenase-2 Mus musculus Inhibition = 9.8 % PMID[14980657]
NPT197 Protein-protein interaction Menin/Histone-lysine N-methyltransferase MLL Homo sapiens Potency = 22387.2 nM PubChem BioAssay data set
NPT539 Individual protein Cellular tumor antigen p53 Homo sapiens Potency = 15848.9 nM PubChem BioAssay data set
NPT539 Individual protein Cellular tumor antigen p53 Homo sapiens Potency = 12589.3 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. deltaA = 0.23 n.a. PMID[20565070]
NPT2 Others Unspecified n.a. Potency = 12589.3 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency = 31622.8 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 7079.5 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Ratio IC50 = 200.0 n.a. PMID[23574272]
NPT2 Others Unspecified n.a. Potency n.a. 5623.4 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 3162.3 nM PubChem BioAssay data set

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 NPC266597 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
0.7925 Intermediate Similarity NPC604422
0.7925 Intermediate Similarity NPC607642
0.7347 Intermediate Similarity NPC172262
0.7273 Intermediate Similarity NPC115323
0.72 Intermediate Similarity NPC57601
0.7037 Intermediate Similarity NPC281207
0.7037 Intermediate Similarity NPC604085
0.6731 Remote Similarity NPC70136
0.6731 Remote Similarity NPC604293
0.6727 Remote Similarity NPC231772
0.6727 Remote Similarity NPC250266
0.6604 Remote Similarity NPC2771
0.6415 Remote Similarity NPC603556
0.625 Remote Similarity NPC156222
0.6167 Remote Similarity NPC295036
0.614 Remote Similarity NPC184136
0.6034 Remote Similarity NPC209560
0.6034 Remote Similarity NPC490700
0.5965 Remote Similarity NPC29353
0.5932 Remote Similarity NPC55205
0.5862 Remote Similarity NPC57030
0.5862 Remote Similarity NPC22519
0.5862 Remote Similarity NPC145379
0.5789 Remote Similarity NPC136840
0.5763 Remote Similarity NPC603662
0.5714 Remote Similarity NPC284424
0.569 Remote Similarity NPC125887
0.569 Remote Similarity NPC47815
0.5625 Remote Similarity NPC261227
0.5593 Remote Similarity NPC260895
0.55 Remote Similarity NPC312924
0.5484 Remote Similarity NPC12175
0.5484 Remote Similarity NPC610914
0.5439 Remote Similarity NPC101294
0.5429 Remote Similarity NPC303485
0.5424 Remote Similarity NPC274327
0.5424 Remote Similarity NPC241498
0.5424 Remote Similarity NPC113089
0.5424 Remote Similarity NPC52611
0.5424 Remote Similarity NPC194281
0.5424 Remote Similarity NPC600177
0.5424 Remote Similarity NPC608872
0.5397 Remote Similarity NPC55162
0.5385 Remote Similarity NPC269906
0.5357 Remote Similarity NPC22783
0.5357 Remote Similarity NPC12367
0.5345 Remote Similarity NPC14958
0.5333 Remote Similarity NPC176775
0.5333 Remote Similarity NPC234133
0.5333 Remote Similarity NPC604462
0.5323 Remote Similarity NPC287101
0.5323 Remote Similarity NPC52005
0.5323 Remote Similarity NPC12200
0.5323 Remote Similarity NPC602125
0.5323 Remote Similarity NPC605336
0.5323 Remote Similarity NPC606525
0.5286 Remote Similarity NPC150908
0.5263 Remote Similarity NPC607644
0.5246 Remote Similarity NPC605047
0.5205 Remote Similarity NPC601565
0.5167 Remote Similarity NPC77955
0.5167 Remote Similarity NPC483774
0.5167 Remote Similarity NPC608264
0.5139 Remote Similarity NPC186227
0.5085 Remote Similarity NPC129680
0.5082 Remote Similarity NPC59951
0.5082 Remote Similarity NPC198826
0.5082 Remote Similarity NPC241838
0.5082 Remote Similarity NPC120163
0.5082 Remote Similarity NPC483773
0.5082 Remote Similarity NPC605146
0.5079 Remote Similarity NPC12377
0.507 Remote Similarity NPC601984

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC266597 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