Natural Product: NPC139813

Natural Product IDNPC139813
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (E)-1-(2-Hydroxy-4-Methoxyphenyl)-3-(4-Methoxyphenyl)Prop-2-En-1-One
IUPAC Name (E)-1-(2-hydroxy-4-methoxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL229907
PubChem CID 5357488
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0001630] Chalcones and dihydrochalcones
          • [CHEMONTID:0003472] 2'-Hydroxychalcones

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 OAAPAFSEMHJNTF-BJMVGYQFSA-N
Standard InCHI InChI=1S/C17H16O4/c1-20-13-6-3-12(4-7-13)5-10-16(18)15-9-8-14(21-2)11-17(15)19/h3-11,19H,1-2H3/b10-5+
SMILES COc1ccc(cc1)/C=C/C(=O)c1ccc(cc1O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   284.1 Volume:   299.545
?
Van der Waals volume.
Dense:   0.948 LogP:   3.337
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.407
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.027
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   14.0
TPSA:   55.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.676 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.854 Fsp3:   0.118
MCE-18:   12.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.965 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.611
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.918
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.863 Promiscuous compounds:   0.593

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.013 MDCK Permeability:   -4.798
Pgp-inhibitor:   0.985 Pgp-substrate:   0.001
PAMPA:   0.004
?
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):   0.147
20% Bioavailability (F20%):   0.861 30% Bioavailability (F30%):   0.969
50% Bioavailability (F50%):   0.972

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.0
Plasma Protein Binding (PPB):   95.578% Volume Distribution (VD):   -0.431
Fu: 3.537%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.99
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.992
CYP2C9-inhibitor:   0.654 CYP2C9-substrate:   0.904
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.355
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.254
?
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):  9.752 Half-life (T1/2):  0.727

ADMET: Toxicity

hERG Blockers:  0.274 hERG Blockers (10um):  0.453
Human Hepatotoxicity (H-HT):  0.498 Drug-induced Liver Injury (DILI):  0.735
AMES Toxicity:  0.528 Rat Oral Acute Toxicity:  0.104
Maximum Recommended Daily Dose:  0.462 Skin Sensitization:  0.545
Carcinogencity:  0.405 Eye Corrosion:  0.11
Eye Irritation:  0.98 Respiratory Toxicity:  0.8
Drug-induced Neurotoxicity:  0.637 Ototoxicity:  0.186
Hematotoxicity:  0.239 Drug-induced Nephrotoxicity:  0.563
Genotoxicity:  0.146 RPMI-8226 Immunitoxicity:  0.124
A549 Cytotoxicity:  0.166 Hek293 Cytotoxicity:  0.456
BCF:   1.507
?
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:   4.369
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.886
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.376
?
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
NPO31363 Rhus sylvestris Species Anacardiaceae Eukaryota stems and leaves n.a. n.a. PMID[19447618]
NPO15828 Garcinia nervosa Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31363 Rhus sylvestris Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15828 Garcinia nervosa Species Clusiaceae 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 = 398.1 nM PubChem BioAssay data set
NPT282 Individual protein MAP kinase ERK2 Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens Potency = 3162.3 nM PubChem BioAssay data set
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens Potency n.a. 6513.1 nM PubChem BioAssay data set
NPT1422 Individual protein ATP-binding cassette sub-family G member 2 Homo sapiens IC50 = 4200.0 nM PMID[22112540]
NPT1422 Individual protein ATP-binding cassette sub-family G member 2 Homo sapiens IC50 = 2200.0 nM PMID[22112540]
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 29092.9 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 20596.2 nM PubChem BioAssay data set
NPT11 Individual protein Guanine nucleotide-binding protein G(s), subunit alpha Homo sapiens Potency n.a. 1995.3 nM PubChem BioAssay data set
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens Potency n.a. 31622.8 nM PubChem BioAssay data set
NPT160 Individual protein TAR DNA-binding protein 43 Homo sapiens Potency n.a. 6309.6 nM PubChem BioAssay data set
NPT1433 Individual protein Serine/threonine-protein kinase Aurora-B Homo sapiens Inhibition = 107.2 % PMID[28064141]
NPT208 Individual protein Cytochrome P450 1A2 Homo sapiens Inhibition = 39.6 % PMID[28064141]
NPT212 Individual protein Cytochrome P450 2C9 Homo sapiens Inhibition = 21.7 % PMID[28064141]
NPT213 Individual protein Cytochrome P450 2C19 Homo sapiens Inhibition = 34.2 % PMID[28064141]
NPT110 Individual protein Cytochrome P450 2D6 Homo sapiens Inhibition = 47.7 % PMID[28064141]
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens Inhibition = 5.0 % PMID[28064141]
NPT483 Individual protein Prelamin-A/C Homo sapiens Potency = 12589.3 nM PubChem BioAssay data set
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 8912.5 nM PubChem BioAssay data set
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 316.2 nM PubChem BioAssay data set
NPT484 Individual protein Luciferin 4-monooxygenase Photinus pyralis Potency n.a. 7568.6 nM PubChem BioAssay data set
NPT41 Individual protein Aldose reductase Homo sapiens Inhibition = 35.0 % PMID[25638569]
NPT98 Individual protein HERG Homo sapiens Inhibition = 2.7 % PMID[28064141]
NPT93 Individual protein Survival motor neuron protein Homo sapiens Potency = 794.3 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 5011.9 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 2511.9 nM PubChem BioAssay data set
NPT8 Individual protein DNA polymerase iota Homo sapiens Potency n.a. 1412.5 nM PubChem BioAssay data set
NPT535 Individual protein Parathyroid hormone receptor Homo sapiens Potency n.a. 39810.7 nM PubChem BioAssay data set
NPT441 Individual protein Cytochrome P450 19A1 Homo sapiens IC50 > 351700.0 nM PMID[17511439]
NPT536 Nucleic acid microRNA 21 Homo sapiens Potency = 14689.2 nM PubChem BioAssay data set
NPT197 Protein-protein interaction Menin/Histone-lysine N-methyltransferase MLL Homo sapiens Potency = 10000.0 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 23109.3 nM PubChem BioAssay data set
NPT78 Individual protein Beta amyloid A4 protein Homo sapiens IC50 = 8400.0 nM PMID[23786711]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 20.9 % PMID[19447618]
NPT926 Cell line SK-MEL-1 Homo sapiens IC50 = 41730.0 nM PMID[19447618]
NPT83 Cell line MCF7 Homo sapiens IC50 = 45390.0 nM PMID[19447618]
NPT165 Cell line HeLa Homo sapiens IC50 > 50000.0 nM PMID[19447618]
NPT81 Cell line A549 Homo sapiens Activity = 101.5 % PMID[28064141]
NPT1374 Cell line WI-38 Homo sapiens Activity = 14.2 % PMID[28064141]
NPT401 Cell line 786-0 Homo sapiens Activity = 14.2 % PMID[28064141]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 9.4 % PMID[28256373]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 3.5 % PMID[28256373]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 54.0 % PMID[28256373]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 78.2 % PMID[28256373]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 4.73 ug.mL-1 PMID[28256373]
NPT113 Cell line RAW264.7 Mus musculus Activity = 93.3 % PMID[28256373]
NPT113 Cell line RAW264.7 Mus musculus Activity = 72.3 % PMID[28256373]
NPT113 Cell line RAW264.7 Mus musculus Activity = 75.2 % PMID[28256373]
NPT113 Cell line RAW264.7 Mus musculus Activity = 72.6 % PMID[28256373]
NPT6530 Cell line MOLM-13 Homo sapiens GI50 > 10000.0 nM PMID[32975953]
NPT1649 Cell line MV4-11 Homo sapiens GI50 > 10000.0 nM PMID[32975953]
NPT1970 Cell line THP-1 Homo sapiens GI50 > 100000.0 nM PMID[32975953]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 70.0 % PMID[32208222]
NPT1970 Cell line THP-1 Homo sapiens CC50 > 100000.0 nM PMID[28064141]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 14715.7 nM PubChem BioAssay data set
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi Inhibition = 47.0 % PMID[28064141]
NPT2 Others Unspecified n.a. Potency n.a. 16360.1 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Inhibition = 83.14 % PMID[21907578]
NPT2 Others Unspecified n.a. Potency n.a. 14125.4 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. IC50 = 15900.0 nM PMID[23786711]
NPT2 Others Unspecified n.a. Inhibition = 35.0 % PMID[25638569]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei Inhibition = 18.0 % PMID[28064141]

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 NPC139813 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
0.85 High Similarity NPC64359
0.8293 Intermediate Similarity NPC205468
0.7674 Intermediate Similarity NPC284556
0.7442 Intermediate Similarity NPC262359
0.7045 Intermediate Similarity NPC242294
0.6889 Remote Similarity NPC605344
0.6522 Remote Similarity NPC265045
0.6383 Remote Similarity NPC56031
0.6364 Remote Similarity NPC212631
0.6364 Remote Similarity NPC188967
0.6364 Remote Similarity NPC608685
0.62 Remote Similarity NPC240593
0.6078 Remote Similarity NPC188879
0.5897 Remote Similarity NPC186098
0.5833 Remote Similarity NPC188646
0.5833 Remote Similarity NPC607239
0.5714 Remote Similarity NPC263670
0.5682 Remote Similarity NPC211120
0.566 Remote Similarity NPC482939
0.56 Remote Similarity NPC144281
0.5556 Remote Similarity NPC25287
0.5556 Remote Similarity NPC176930
0.5556 Remote Similarity NPC485640
0.5556 Remote Similarity NPC602047
0.54 Remote Similarity NPC93034
0.5357 Remote Similarity NPC154304
0.5333 Remote Similarity NPC19174
0.5333 Remote Similarity NPC115159
0.5294 Remote Similarity NPC471417
0.5254 Remote Similarity NPC294387
0.5208 Remote Similarity NPC192304
0.52 Remote Similarity NPC312318
0.52 Remote Similarity NPC142165
0.5192 Remote Similarity NPC473391
0.5192 Remote Similarity NPC254659
0.5185 Remote Similarity NPC482977
0.5156 Remote Similarity NPC488085
0.5128 Remote Similarity NPC99886
0.5128 Remote Similarity NPC259134
0.5128 Remote Similarity NPC8002
0.5106 Remote Similarity NPC297186
0.5102 Remote Similarity NPC257756
0.5102 Remote Similarity NPC336114
0.5098 Remote Similarity NPC119660
0.5098 Remote Similarity NPC87231
0.5098 Remote Similarity NPC129132
0.5094 Remote Similarity NPC472364
0.5091 Remote Similarity NPC269694
0.5085 Remote Similarity NPC190487

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC139813 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