Natural Product: NPC248817

Natural Product IDNPC248817
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4-Propenyl-Phenol
IUPAC Name 4-[(E)-prop-1-enyl]phenol
Synonyms 4-Propenyl-Phenol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL163297
PubChem CID 5474441
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000037] Styrenes

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 UMFCIIBZHQXRCJ-NSCUHMNNSA-N
Standard InCHI InChI=1S/C9H10O/c1-2-3-8-4-6-9(10)7-5-8/h2-7,10H,1H3/b3-2+
SMILES C/C=C/c1ccc(cc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   134.07 Volume:   153.908
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Van der Waals volume.
Dense:   0.871 LogP:   2.322
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.306
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.272
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   7.0
TPSA:   20.23
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Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.625 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.906 Fsp3:   0.111
MCE-18:   5.0
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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:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.066 Fluc inhibitor:   0.933
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.006
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.002
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   1.0 Promiscuous compounds:   0.689

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.853 MDCK Permeability:   -4.762
Pgp-inhibitor:   0.105 Pgp-substrate:   0.065
PAMPA:   0.087
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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):   0.004
20% Bioavailability (F20%):   0.645 30% Bioavailability (F30%):   0.61
50% Bioavailability (F50%):   0.983

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.019 MRP1:   0.444
Plasma Protein Binding (PPB):   98.857% Volume Distribution (VD):   -0.115
Fu: 1.472%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.955
OATP1B3 inhibitor:   0.97 BCRP inhibitor:   0.423
BSEP inhibitor:   0.956

ADMET: Metabolism

CYP1A2-inhibitor:   0.453 CYP1A2-substrate:   0.46
CYP2C19-inhibitor:   0.055 CYP2C19-substrate:   0.683
CYP2C9-inhibitor:   0.133 CYP2C9-substrate:   0.113
CYP2D6-inhibitor:   0.995 CYP2D6-substrate:   0.313
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.003 CYP2C8-inhibitor:   0.999
HLM stability:   0.66
?
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):  10.586 Half-life (T1/2):  0.988

ADMET: Toxicity

hERG Blockers:  0.221 hERG Blockers (10um):  0.556
Human Hepatotoxicity (H-HT):  0.546 Drug-induced Liver Injury (DILI):  0.142
AMES Toxicity:  0.402 Rat Oral Acute Toxicity:  0.182
Maximum Recommended Daily Dose:  0.282 Skin Sensitization:  0.955
Carcinogencity:  0.462 Eye Corrosion:  0.961
Eye Irritation:  0.997 Respiratory Toxicity:  0.58
Drug-induced Neurotoxicity:  0.66 Ototoxicity:  0.167
Hematotoxicity:  0.086 Drug-induced Nephrotoxicity:  0.188
Genotoxicity:  0.135 RPMI-8226 Immunitoxicity:  0.051
A549 Cytotoxicity:  0.177 Hek293 Cytotoxicity:  0.328
BCF:   1.742
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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:   3.87
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.771
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.051
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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
NPO16682 Cirsium chinense Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10786 Trichocereus werdermannianus Species Cactaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7250 Ventilago vitiensis Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12940 Briareum stechei Species Briareidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10079 Chloropyron maritimum Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5531 Protoceratium reticulatum Species Gonyaulacaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16682 Cirsium chinense Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16682 Cirsium chinense Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7250 Ventilago vitiensis Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10786 Trichocereus werdermannianus Species Cactaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5531 Protoceratium reticulatum Species Gonyaulacaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16682 Cirsium chinense Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10079 Chloropyron maritimum Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12940 Briareum stechei Species Briareidae 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
NPT2805 Individual protein Dopamine beta-hydroxylase Bos taurus Ki > 20000000.0 nM PMID[2704022]
NPT2805 Individual protein Dopamine beta-hydroxylase Bos taurus Partition ratio = 680.0 n.a. PMID[2704022]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC248817 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
0.6923 Remote Similarity NPC239808
0.6786 Remote Similarity NPC181709
0.6667 Remote Similarity NPC104216
0.6552 Remote Similarity NPC184169
0.6429 Remote Similarity NPC286006
0.625 Remote Similarity NPC265146
0.5806 Remote Similarity NPC68269
0.5758 Remote Similarity NPC171843
0.5625 Remote Similarity NPC82664
0.5625 Remote Similarity NPC253746
0.5625 Remote Similarity NPC132271
0.5625 Remote Similarity NPC98382
0.5625 Remote Similarity NPC292730
0.5625 Remote Similarity NPC216520
0.5625 Remote Similarity NPC17525
0.5588 Remote Similarity NPC304638
0.52 Remote Similarity NPC269586
0.5135 Remote Similarity NPC98772

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC248817 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