Natural Product: NPC323103

Natural Product IDNPC323103
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2-Phenylethyl Butanoate
IUPAC Name 2-phenylethyl butanoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3187974
PubChem CID 7658
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0000324] Fatty 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 WFNDDSQUKATKNX-UHFFFAOYSA-N
Standard InCHI InChI=1S/C12H16O2/c1-2-6-12(13)14-10-9-11-7-4-3-5-8-11/h3-5,7-8H,2,6,9-10H2,1H3
SMILES CCCC(=O)OCCc1ccccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   192.12 Volume:   214.586
?
Van der Waals volume.
Dense:   0.895 LogP:   3.387
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.031
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.428
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   7.0
TPSA:   26.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.67 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.542 Fsp3:   0.417
MCE-18:   5.0
?
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:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.017 Fluc inhibitor:   0.017
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.017
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.223
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.998 Promiscuous compounds:   0.122

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.525 MDCK Permeability:   -4.364
Pgp-inhibitor:   0.953 Pgp-substrate:   0.506
PAMPA:   0.155
?
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):   0.252
20% Bioavailability (F20%):   0.495 30% Bioavailability (F30%):   0.668
50% Bioavailability (F50%):   0.951

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.841 MRP1:   0.519
Plasma Protein Binding (PPB):   81.927% Volume Distribution (VD):   -0.16
Fu: 17.907%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.719
OATP1B3 inhibitor:   0.598 BCRP inhibitor:   0.404
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   0.864 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.013 CYP2C19-substrate:   0.99
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.083
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.807
CYP3A4-inhibitor:   0.863 CYP3A4-substrate:   0.798
CYP2B6-substrate:   0.149 CYP2C8-inhibitor:   0.999
HLM stability:   1.0
?
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):  7.281 Half-life (T1/2):  0.365

ADMET: Toxicity

hERG Blockers:  0.182 hERG Blockers (10um):  0.667
Human Hepatotoxicity (H-HT):  0.234 Drug-induced Liver Injury (DILI):  0.138
AMES Toxicity:  0.202 Rat Oral Acute Toxicity:  0.085
Maximum Recommended Daily Dose:  0.169 Skin Sensitization:  0.746
Carcinogencity:  0.493 Eye Corrosion:  0.88
Eye Irritation:  0.984 Respiratory Toxicity:  0.213
Drug-induced Neurotoxicity:  0.385 Ototoxicity:  0.169
Hematotoxicity:  0.187 Drug-induced Nephrotoxicity:  0.29
Genotoxicity:  0.006 RPMI-8226 Immunitoxicity:  0.034
A549 Cytotoxicity:  0.026 Hek293 Cytotoxicity:  0.087
BCF:   0.689
?
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:   3.193
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.395
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.994
?
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
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. Nigeria(latitude 80°N and longitude 4°E) 2005; 2006 DOI[10.1002/ejlt.201000080]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11240-015-0761-z]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11306-010-0259-y]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11306-014-0638-x]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s11746-997-0093-1]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s12010-013-0354-4]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.jarmap.2018.11.004]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.phytol.2008.07.007]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Seeds Plovdiv, Plovdiv region in South Bulgaria DOI[10.1051/CTV/20163101031]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1055/S-2006-958077]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1186/s40064-015-0831-z]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. DOI[10.1501/Tarimbil_0000001065]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. PMID[11170689]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. leaf n.a. PMID[11312782]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. fruit n.a. PMID[11312782]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. PMID[11408943]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. fruit n.a. PMID[12105962]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. Esuela Tecnica Superior de Ingenieros Agrónomos de Albacete 2007 PMID[19256538]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. PMID[20826702]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. PMID[22537213]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. PMID[23759170]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Stalks n.a. n.a. PMID[24521157]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Seeds Benedictine Pannonhalma Archabbey, Hungary PMID[29803478]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. PMID[31433178]
NPO2613 Artemisia ordosica Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[36558030]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. PMID[37446586]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. PMID[37570937]
NPO16116 Aniba canelilla Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[38005295]
NPO16116 Aniba canelilla Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2613 Artemisia ordosica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Fruits n.a. Database[FooDB]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. Database[FooDB]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Stem n.a. n.a. Database[FooDB]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Leaf Essent. Oil n.a. n.a. Database[FooDB]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. Database[MetaboLights]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17024 Vitis vinifera Species Vitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16116 Aniba canelilla Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2613 Artemisia ordosica Species Asteraceae 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
NPO16116 Aniba canelilla Oil n.a. 0.1 n.a. n.a. % PMID[38005295]
NPO2613 Artemisia ordosica Oil Aerial parts 0.17 n.a. n.a. % PMID[36558030]

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
NPT163 Individual protein Nuclear factor NF-kappa-B p105 subunit Homo sapiens Potency n.a. 2.8 nM PubChem BioAssay data set
NPT346 Individual protein Transient receptor potential cation channel subfamily A member 1 Homo sapiens Activity = 62.0 % PMID[32249116]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT71 Cell line HEK293 Homo sapiens CC50 > 20000.0 nM DOI[10.6019/CHEMBL4513161]
NPT20 Organism Candida albicans Candida albicans MIC > 20000.0 nM DOI[10.6019/CHEMBL4513161]
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae MIC > 20000.0 nM DOI[10.6019/CHEMBL4513161]
NPT19 Organism Escherichia coli Escherichia coli MIC > 20000.0 nM DOI[10.6019/CHEMBL4513161]
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC > 20000.0 nM DOI[10.6019/CHEMBL4513161]
NPT20950 Cell line Erythrocyte n.a. HC10 > 20.0 uM DOI[10.6019/CHEMBL4513161]
NPT2 Others Unspecified n.a. Potency n.a. 4364.7 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 21875.1 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 1737.6 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 68589.6 nM PubChem BioAssay data set
NPT747 Organism Acinetobacter baumannii Acinetobacter baumannii MIC > 20000.0 nM DOI[10.6019/CHEMBL4513161]

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
- Rattus norvegicus LD50 = 4.6 mL/kg ToxVal
- Rattus norvegicus LD50 = 4590.8 mg/kg ToxVal
- Oryctolagus cuniculus LD50 > 4990.0 mg/kg ToxVal
- Homo sapiens DNEL systemic = 16.4 mg/m3 ToxVal

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 NPC323103 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
0.8438 Intermediate Similarity NPC604949
0.8065 Intermediate Similarity NPC121800
0.7097 Intermediate Similarity NPC170484
0.6471 Remote Similarity NPC103387
0.6389 Remote Similarity NPC270507
0.6 Remote Similarity NPC9822
0.5714 Remote Similarity NPC31274
0.55 Remote Similarity NPC213156
0.55 Remote Similarity NPC240108
0.525 Remote Similarity NPC185501

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC323103 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