Natural Product: NPC128730

Natural Product IDNPC128730
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Methyl 3-(4-(Buta-2,3-Dienyloxy)Phenyl)Acrylate
IUPAC Name methyl (E)-3-(4-buta-2,3-dienoxyphenyl)prop-2-enoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL230589
PubChem CID 10014072
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 LUTXPQCBZWHPTG-JXMROGBWSA-N
Standard InCHI InChI=1S/C14H14O3/c1-3-4-11-17-13-8-5-12(6-9-13)7-10-14(15)16-2/h4-10H,1,11H2,2H3/b10-7+
SMILES C=C=CCOc1ccc(cc1)/C=C/C(=O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   230.09 Volume:   250.059
?
Van der Waals volume.
Dense:   0.92 LogP:   2.957
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.701
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.166
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   10.0
TPSA:   35.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.443 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.516 Fsp3:   0.143
MCE-18:   6.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.733 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.041
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.636
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.998 Promiscuous compounds:   0.068

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.523 MDCK Permeability:   -4.506
Pgp-inhibitor:   0.995 Pgp-substrate:   0.012
PAMPA:   0.092
?
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):   0.291
20% Bioavailability (F20%):   0.942 30% Bioavailability (F30%):   0.869
50% Bioavailability (F50%):   0.858

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.0
Plasma Protein Binding (PPB):   89.496% Volume Distribution (VD):   -0.039
Fu: 11.566%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.844
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.057 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.967
CYP2C9-inhibitor:   0.508 CYP2C9-substrate:   0.142
CYP2D6-inhibitor:   0.946 CYP2D6-substrate:   0.004
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.467
?
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):  10.519 Half-life (T1/2):  0.952

ADMET: Toxicity

hERG Blockers:  0.247 hERG Blockers (10um):  0.692
Human Hepatotoxicity (H-HT):  0.497 Drug-induced Liver Injury (DILI):  0.547
AMES Toxicity:  0.783 Rat Oral Acute Toxicity:  0.45
Maximum Recommended Daily Dose:  0.559 Skin Sensitization:  0.974
Carcinogencity:  0.487 Eye Corrosion:  0.882
Eye Irritation:  0.984 Respiratory Toxicity:  0.935
Drug-induced Neurotoxicity:  0.349 Ototoxicity:  0.148
Hematotoxicity:  0.013 Drug-induced Nephrotoxicity:  0.392
Genotoxicity:  0.015 RPMI-8226 Immunitoxicity:  0.039
A549 Cytotoxicity:  0.029 Hek293 Cytotoxicity:  0.257
BCF:   1.367
?
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:   3.922
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.539
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.017
?
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
NPO16586 Lepechinia bullata Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[2778450]
NPO15383 Carapa guianensis Species Meliaceae Eukaryota n.a. n.a. n.a. PMID[37371565]
NPO16586 Lepechinia bullata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3305 Andropogon odoratus Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9914 Athrotaxis laxifolia Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15383 Carapa guianensis Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25596 Leptopetalum biflorum Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13367 Nauclea calycina Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO467 Stachys africana Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9914 Athrotaxis laxifolia Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3305 Andropogon odoratus Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16586 Lepechinia bullata Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25596 Leptopetalum biflorum Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO467 Stachys africana Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13367 Nauclea calycina Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15383 Carapa guianensis Species Meliaceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT91 Cell line KB Homo sapiens IC50 = 27640.0 nM PMID[17387015]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 18960.0 nM PMID[17387015]

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 NPC128730 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
0.7381 Intermediate Similarity NPC176971
0.62 Remote Similarity NPC157473
0.62 Remote Similarity NPC151530
0.5682 Remote Similarity NPC179686
0.5227 Remote Similarity NPC8302
0.5122 Remote Similarity NPC287790
0.5122 Remote Similarity NPC3672

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC128730 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
0.5102 Remote Similarity NPD1358 Phase 4

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