Natural Product: NPC92722

Natural Product IDNPC92722
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (E)-1-(2,3-Dihydroxy-4,6-Dimethoxyphenyl)-3-Phenylprop-2-En-1-One
IUPAC Name (E)-1-(2,3-dihydroxy-4,6-dimethoxyphenyl)-3-phenylprop-2-en-1-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1446527
PubChem CID 14159747
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 IAYOHSHBLLHXFB-CMDGGOBGSA-N
Standard InCHI InChI=1S/C17H16O5/c1-21-13-10-14(22-2)16(19)17(20)15(13)12(18)9-8-11-6-4-3-5-7-11/h3-10,19-20H,1-2H3/b9-8+
SMILES COc1cc(OC)c(c(c1C(=O)/C=C/c1ccccc1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.1 Volume:   308.335
?
Van der Waals volume.
Dense:   0.973 LogP:   2.477
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.373
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.681
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   14.0
TPSA:   75.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.504 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.17 Fsp3:   0.118
MCE-18:   13.0
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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:   1 PAINS Alert:   1
Colloidal aggregators:   0.774 Fluc inhibitor:   0.999
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.613
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.851
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.581 Promiscuous compounds:   0.536

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.999 MDCK Permeability:   -4.797
Pgp-inhibitor:   0.983 Pgp-substrate:   0.003
PAMPA:   0.01
?
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):   0.02
20% Bioavailability (F20%):   0.252 30% Bioavailability (F30%):   0.673
50% Bioavailability (F50%):   0.888

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.012 MRP1:   0.102
Plasma Protein Binding (PPB):   98.763% Volume Distribution (VD):   -0.613
Fu: 0.746%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.915
BSEP inhibitor:   0.985

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.974
CYP2C9-inhibitor:   0.976 CYP2C9-substrate:   0.041
CYP2D6-inhibitor:   0.994 CYP2D6-substrate:   0.043
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.047
?
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):  8.437 Half-life (T1/2):  0.94

ADMET: Toxicity

hERG Blockers:  0.223 hERG Blockers (10um):  0.551
Human Hepatotoxicity (H-HT):  0.618 Drug-induced Liver Injury (DILI):  0.605
AMES Toxicity:  0.343 Rat Oral Acute Toxicity:  0.157
Maximum Recommended Daily Dose:  0.44 Skin Sensitization:  0.802
Carcinogencity:  0.247 Eye Corrosion:  0.12
Eye Irritation:  0.982 Respiratory Toxicity:  0.571
Drug-induced Neurotoxicity:  0.706 Ototoxicity:  0.209
Hematotoxicity:  0.265 Drug-induced Nephrotoxicity:  0.334
Genotoxicity:  0.125 RPMI-8226 Immunitoxicity:  0.077
A549 Cytotoxicity:  0.231 Hek293 Cytotoxicity:  0.352
BCF:   1.212
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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:   4.003
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.146
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.767
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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
NPO1635 Didymocarpus pedicellata Species Gesneriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15046 Neonauclea zeylanica Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17692.1 Rhizopus microsporus var. chinensis Varieties Rhizopodaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25598 Sporidesmium bakeri Species n.a. Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12203 Uvaria dulcis Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12203 Uvaria dulcis Species Annonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1635 Didymocarpus pedicellata Species Gesneriaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15046 Neonauclea zeylanica Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1635 Didymocarpus pedicellata Species Gesneriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12203 Uvaria dulcis Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25598 Sporidesmium bakeri Species n.a. Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17692.1 Rhizopus microsporus var. chinensis Varieties Rhizopodaceae 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
NPT3 Individual protein Thioredoxin glutathione reductase Schistosoma mansoni Potency = 39810.7 nM PubChem BioAssay data set
NPT1416 Individual protein Neuropeptide S receptor Homo sapiens Potency = 10000.0 nM PubChem BioAssay data set
NPT198 Individual protein Vitamin D receptor Homo sapiens Potency n.a. 50118.7 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 18356.4 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 23109.3 nM PubChem BioAssay data set
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT160 Individual protein TAR DNA-binding protein 43 Homo sapiens Potency n.a. 12589.3 nM PubChem BioAssay data set
NPT11 Individual protein Guanine nucleotide-binding protein G(s), subunit alpha Homo sapiens Potency n.a. 28183.8 nM PubChem BioAssay data set
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 10000.0 nM PubChem BioAssay data set
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 17782.8 nM PubChem BioAssay data set
NPT9 Individual protein DNA polymerase eta Homo sapiens Potency n.a. 79432.8 nM PubChem BioAssay data set
NPT54 Individual protein Nonstructural protein 1 Influenza A virus Potency = 12589.3 nM PubChem BioAssay data set
NPT7 Individual protein Thioredoxin reductase 1, cytoplasmic Rattus norvegicus Potency n.a. 89125.1 nM PubChem BioAssay data set
NPT484 Individual protein Luciferin 4-monooxygenase Photinus pyralis Potency n.a. 21331.3 nM PubChem BioAssay data set
NPT477 Individual protein DNA dC->dU-editing enzyme APOBEC-3G Homo sapiens Potency n.a. 25118.9 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 12589.3 nM PubChem BioAssay data set
NPT63 Individual protein Bromodomain adjacent to zinc finger domain protein 2B Homo sapiens Potency n.a. 44668.4 nM PubChem BioAssay data set
NPT8 Individual protein DNA polymerase iota Homo sapiens Potency n.a. 5011.9 nM PubChem BioAssay data set
NPT478 Individual protein Ataxin-2 Homo sapiens Potency n.a. 44668.4 nM PubChem BioAssay data set
NPT535 Individual protein Parathyroid hormone receptor Homo sapiens Potency n.a. 44668.4 nM PubChem BioAssay data set
NPT536 Nucleic acid microRNA 21 Homo sapiens Potency = 23280.9 nM PubChem BioAssay data set
NPT532 Individual protein Lysine-specific demethylase 4A Homo sapiens Potency n.a. 56234.1 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 11689.1 nM PubChem BioAssay data set
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 18526.0 nM PubChem BioAssay data set
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae Potency = 15848.9 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 8912.5 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 22387.2 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 14125.4 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 25118.9 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 NPC92722 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
0.6875 Remote Similarity NPC188646
0.6078 Remote Similarity NPC87231
0.5962 Remote Similarity NPC150399
0.5893 Remote Similarity NPC11561
0.5882 Remote Similarity NPC131451
0.5769 Remote Similarity NPC156092
0.5769 Remote Similarity NPC15329
0.5714 Remote Similarity NPC212631
0.5714 Remote Similarity NPC608685
0.5686 Remote Similarity NPC242294
0.5577 Remote Similarity NPC308037
0.5577 Remote Similarity NPC477243
0.5556 Remote Similarity NPC473391
0.549 Remote Similarity NPC64359
0.5472 Remote Similarity NPC263670
0.5455 Remote Similarity NPC472364
0.5417 Remote Similarity NPC58229
0.5283 Remote Similarity NPC142165
0.5231 Remote Similarity NPC91288
0.5091 Remote Similarity NPC476333
0.5091 Remote Similarity NPC175098
0.5091 Remote Similarity NPC471417
0.5091 Remote Similarity NPC337373
0.5088 Remote Similarity NPC472368

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC92722 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