Natural Product: NPC203076

Natural Product IDNPC203076
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (E)-3-Phenyl-N-(2-Phenylethyl)Prop-2-Enamide
IUPAC Name (E)-3-phenyl-N-(2-phenylethyl)prop-2-enamide
Synonyms N-Phenethylcinnamamide
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1305393
PubChem CID 795855
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000476] Cinnamic acids and derivatives
        • [CHEMONTID:0002810] Cinnamic acid amides

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 BOSUEWCVNFFBGV-VAWYXSNFSA-N
Standard InCHI InChI=1S/C17H17NO/c19-17(12-11-15-7-3-1-4-8-15)18-14-13-16-9-5-2-6-10-16/h1-12H,13-14H2,(H,18,19)/b12-11+
SMILES OC(=NCCc1ccccc1)/C=C/c1ccccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   251.13 Volume:   284.171
?
Van der Waals volume.
Dense:   0.884 LogP:   3.455
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.975
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.988
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   14.0
TPSA:   32.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.634 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.137 Fsp3:   0.118
MCE-18:   9.0
?
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:   0.973 Fluc inhibitor:   0.999
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.109
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.855
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.146 Promiscuous compounds:   0.259

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.542 MDCK Permeability:   -4.58
Pgp-inhibitor:   0.757 Pgp-substrate:   0.119
PAMPA:   0.119
?
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%):   0.774 30% Bioavailability (F30%):   0.936
50% Bioavailability (F50%):   0.99

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.038 MRP1:   0.016
Plasma Protein Binding (PPB):   98.386% Volume Distribution (VD):   -0.013
Fu: 0.614%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.975
OATP1B3 inhibitor:   0.734 BCRP inhibitor:   0.01
BSEP inhibitor:   0.992

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   0.997
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.901
CYP2C9-inhibitor:   0.989 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.99
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.116
?
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):  10.421 Half-life (T1/2):  0.84

ADMET: Toxicity

hERG Blockers:  0.375 hERG Blockers (10um):  0.486
Human Hepatotoxicity (H-HT):  0.924 Drug-induced Liver Injury (DILI):  0.704
AMES Toxicity:  0.611 Rat Oral Acute Toxicity:  0.38
Maximum Recommended Daily Dose:  0.568 Skin Sensitization:  0.993
Carcinogencity:  0.362 Eye Corrosion:  0.003
Eye Irritation:  0.716 Respiratory Toxicity:  0.789
Drug-induced Neurotoxicity:  0.447 Ototoxicity:  0.435
Hematotoxicity:  0.193 Drug-induced Nephrotoxicity:  0.632
Genotoxicity:  0.292 RPMI-8226 Immunitoxicity:  0.012
A549 Cytotoxicity:  0.104 Hek293 Cytotoxicity:  0.281
BCF:   1.161
?
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:   3.694
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.561
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.3
?
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
NPO16230 Malus pumila Species Rosaceae Eukaryota Fruit n.a. n.a. DOI[10.1021/jf970571j]
NPO16230 Malus pumila Species Rosaceae Eukaryota n.a. fruit n.a. PMID[240326]
NPO17322 Bosistoa selwynii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16028 Chilocorus cacti Species Coccinellidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14515 Peschiera affinis n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO8707.1 Pueraria montana var. lobata Varieties Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16230 Malus pumila Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16230 Malus pumila Species Rosaceae Eukaryota Fruits n.a. Database[FooDB]
NPO16230 Malus pumila Species Rosaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO16230 Malus pumila Species Rosaceae Eukaryota Pollen Or Spore n.a. n.a. Database[FooDB]
NPO16230 Malus pumila Species Rosaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO16230 Malus pumila Species Rosaceae Eukaryota Pericarp n.a. n.a. Database[FooDB]
NPO16230 Malus pumila Species Rosaceae Eukaryota n.a. n.a. Database[FooDB]
NPO16230 Malus pumila Species Rosaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO16230 Malus pumila Species Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8707.1 Pueraria montana var. lobata Varieties Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16230 Malus pumila Species Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8707.1 Pueraria montana var. lobata Varieties Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO17561 Astragalus coluteocarpus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16230 Malus pumila Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16028 Chilocorus cacti Species Coccinellidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17833 Croton membranaceus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8707.1 Pueraria montana var. lobata Varieties Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17322 Bosistoa selwynii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14515 Peschiera affinis n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO13819 Polyanthina nemorosa n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO5106 Sphaeria herpotrichoides n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO16230 Malus pumila Species Rosaceae Eukaryota Fruit n.a. n.a. Database[USDA]

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
NPT1254 Individual protein Streptokinase A Streptococcus pyogenes serotype M1 EC50 > 150000.0 nM PubChem BioAssay data set
NPT1254 Individual protein Streptokinase A Streptococcus pyogenes serotype M1 EC50 = 48666.0 nM PubChem BioAssay data set
NPT199 Individual protein DNA polymerase kappa Homo sapiens Potency n.a. 56234.1 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 65.1 nM PubChem BioAssay data set
NPT280 Individual protein Matrix metalloproteinase 9 Homo sapiens IC50 = 8.19 nM PMID[23375794]
NPT1854 Individual protein Phosphoglycerate kinase Trypanosoma brucei brucei (strain 927/4 GUTat10.1) Potency n.a. 20574.9 nM PubChem BioAssay data set
NPT533 Protein-protein interaction Runt-related transcription factor 1/Core-binding factor subunit beta Homo sapiens Potency n.a. 31622.8 nM PubChem BioAssay data set
NPT9 Individual protein DNA polymerase eta Homo sapiens Potency n.a. 19952.6 nM PubChem BioAssay data set
NPT9 Individual protein DNA polymerase eta Homo sapiens Potency n.a. 67455.5 nM PubChem BioAssay data set
NPT484 Individual protein Luciferin 4-monooxygenase Photinus pyralis Potency n.a. 19011.5 nM PubChem BioAssay data set
NPT69 Individual protein Matrix metalloproteinase-1 Homo sapiens IC50 = 3252.67 nM PMID[23375794]
NPT59 Individual protein DNA polymerase beta Homo sapiens Potency = 25118.9 nM PubChem BioAssay data set
NPT63 Individual protein Bromodomain adjacent to zinc finger domain protein 2B Homo sapiens Potency n.a. 79432.8 nM PubChem BioAssay data set
NPT8 Individual protein DNA polymerase iota Homo sapiens Potency n.a. 56234.1 nM PubChem BioAssay data set
NPT534 Individual protein Phosphoglycerate kinase, glycosomal Trypanosoma brucei brucei Potency n.a. 28183.8 nM PubChem BioAssay data set
NPT535 Individual protein Parathyroid hormone receptor Homo sapiens Potency n.a. 14125.4 nM PubChem BioAssay data set
NPT8 Individual protein DNA polymerase iota Homo sapiens Potency n.a. 67015.8 nM PubChem BioAssay data set
NPT47 Individual protein ATP-dependent DNA helicase Q1 Homo sapiens Potency = 17782.8 nM PubChem BioAssay data set
NPT536 Nucleic acid microRNA 21 Homo sapiens Potency = 3689.8 nM PubChem BioAssay data set
NPT47 Individual protein ATP-dependent DNA helicase Q1 Homo sapiens Potency = 354.8 nM PubChem BioAssay data set
NPT532 Individual protein Lysine-specific demethylase 4A Homo sapiens Potency n.a. 44668.4 nM PubChem BioAssay data set
NPT443 Individual protein Histone acetyltransferase GCN5 Homo sapiens Potency n.a. 39810.7 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 20587.8 nM PubChem BioAssay data set
NPT47 Individual protein ATP-dependent DNA helicase Q1 Homo sapiens Potency n.a. 39810.7 nM PubChem BioAssay data set
NPT568 Individual protein Matrix metalloproteinase-2 Homo sapiens IC50 = 9.13 nM PMID[23375794]
NPT49 Individual protein DNA-(apurinic or apyrimidinic site) lyase Homo sapiens Potency n.a. 7943.3 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT174 Organism Streptococcus Streptococcus EC50 > 150000.0 nM PubChem BioAssay data set
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 82.8 nM PubChem BioAssay data set
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 928.5 nM PubChem BioAssay data set
NPT1252 Organism Streptococcus sp. 'group A' Streptococcus sp. 'group A' EC50 > 150000.0 nM PubChem BioAssay data set
NPT22401 Selectivity group MMP-1/MMP-2 Homo sapiens Ratio IC50 = 356.0 n.a. PMID[23375794]
NPT2 Others Unspecified n.a. Potency = 56234.1 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. 12589.3 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Ratio IC50 = 397.0 n.a. PMID[23375794]
NPT2 Others Unspecified n.a. Potency n.a. 3981.1 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 NPC203076 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
0.8095 Intermediate Similarity NPC96224
0.7674 Intermediate Similarity NPC283468
0.6977 Remote Similarity NPC24101
0.6939 Remote Similarity NPC263835
0.6875 Remote Similarity NPC301713
0.6471 Remote Similarity NPC155838
0.617 Remote Similarity NPC122009
0.617 Remote Similarity NPC480468
0.5577 Remote Similarity NPC282531
0.5577 Remote Similarity NPC251571
0.5472 Remote Similarity NPC61879
0.5472 Remote Similarity NPC296898
0.5306 Remote Similarity NPC33168
0.5273 Remote Similarity NPC52029
0.5273 Remote Similarity NPC195749
0.5273 Remote Similarity NPC35961
0.5185 Remote Similarity NPC214869

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC203076 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