Natural Product: NPC213156

Natural Product IDNPC213156
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (Z)-Phenethyl 3-Phenylacrylate
IUPAC Name 2-phenylethyl (Z)-3-phenylprop-2-enoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2252207
PubChem CID 25022053
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000476] Cinnamic acids and derivatives
        • [CHEMONTID:0003480] Cinnamic acid esters

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 MJQVZIANGRDJBT-QXMHVHEDSA-N
Standard InCHI InChI=1S/C17H16O2/c18-17(12-11-15-7-3-1-4-8-15)19-14-13-16-9-5-2-6-10-16/h1-12H,13-14H2/b12-11-
SMILES c1ccc(cc1)/C=CC(=O)OCCc1ccccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   252.12 Volume:   281.964
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Van der Waals volume.
Dense:   0.894 LogP:   4.1
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.705
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.083
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   14.0
TPSA:   26.3
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Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.601 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.636 Fsp3:   0.118
MCE-18:   9.0
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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:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.958 Fluc inhibitor:   1.0
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.18
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.787
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.989 Promiscuous compounds:   0.593

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.899 MDCK Permeability:   -4.68
Pgp-inhibitor:   0.999 Pgp-substrate:   0.002
PAMPA:   0.037
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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):   0.029
20% Bioavailability (F20%):   0.299 30% Bioavailability (F30%):   0.635
50% Bioavailability (F50%):   0.792

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.679 MRP1:   0.066
Plasma Protein Binding (PPB):   97.17% Volume Distribution (VD):   0.057
Fu: 2.893%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.953
OATP1B3 inhibitor:   0.783 BCRP inhibitor:   0.042
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.124 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.127 CYP2C9-substrate:   0.84
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.963
CYP3A4-inhibitor:   0.022 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   1.0
HLM stability:   0.988
?
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):  9.063 Half-life (T1/2):  0.424

ADMET: Toxicity

hERG Blockers:  0.645 hERG Blockers (10um):  0.839
Human Hepatotoxicity (H-HT):  0.645 Drug-induced Liver Injury (DILI):  0.012
AMES Toxicity:  0.353 Rat Oral Acute Toxicity:  0.049
Maximum Recommended Daily Dose:  0.215 Skin Sensitization:  1.0
Carcinogencity:  0.025 Eye Corrosion:  0.585
Eye Irritation:  0.983 Respiratory Toxicity:  0.286
Drug-induced Neurotoxicity:  0.817 Ototoxicity:  0.172
Hematotoxicity:  0.014 Drug-induced Nephrotoxicity:  0.44
Genotoxicity:  0.003 RPMI-8226 Immunitoxicity:  0.032
A549 Cytotoxicity:  0.554 Hek293 Cytotoxicity:  0.291
BCF:   1.396
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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:   4.467
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.434
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.22
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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
NPO32976 balantiopsis cancellata Species Balantiopsidaceae Eukaryota n.a. Chile n.a. PMID[15656657]
NPO32976 balantiopsis cancellata Species Balantiopsidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT776 Organism Spodoptera littoralis Spodoptera littoralis Ratio = 0.5 n.a. PMID[15730248]

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 salina LC50 < 2.5 ppm PMID[19928832]

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 NPC213156 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
1.0 High Similarity NPC240108
0.7209 Intermediate Similarity NPC263386
0.7209 Intermediate Similarity NPC141791
0.6944 Remote Similarity NPC167577
0.6579 Remote Similarity NPC208183
0.6579 Remote Similarity NPC176228
0.6579 Remote Similarity NPC243289
0.641 Remote Similarity NPC303245
0.6327 Remote Similarity NPC120225
0.6111 Remote Similarity NPC287790
0.6111 Remote Similarity NPC3672
0.5854 Remote Similarity NPC185501
0.5833 Remote Similarity NPC170484
0.5789 Remote Similarity NPC121800
0.5652 Remote Similarity NPC147654
0.5641 Remote Similarity NPC89950
0.5532 Remote Similarity NPC271641
0.55 Remote Similarity NPC323103
0.5435 Remote Similarity NPC260952
0.5385 Remote Similarity NPC9822
0.5385 Remote Similarity NPC103387
0.5366 Remote Similarity NPC119631
0.5366 Remote Similarity NPC270507
0.5366 Remote Similarity NPC603212
0.5366 Remote Similarity NPC604949
0.5227 Remote Similarity NPC479437
0.5102 Remote Similarity NPC277460
0.5094 Remote Similarity NPC213552

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC213156 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