Natural Product: NPC539314

Natural Product IDNPC539314
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3,4-Methylenedioxycinnamaldehyde
IUPAC Name 3-(1,3-benzodioxol-5-yl)prop-2-enal
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000296] Benzodioxoles

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 HZUFMSJUNLSDSZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C10H8O3/c11-5-1-2-8-3-4-9-10(6-8)13-7-12-9/h1-6H,7H2
SMILES O=CC=CC1=CC=C2OCOC2=C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   176.05 Volume:   177.592
?
Van der Waals volume.
Dense:   0.991 LogP:   2.2
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.072
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.524
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   12.0
TPSA:   35.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.507 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.317 Fsp3:   0.1
MCE-18:   19.636
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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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.686 Fluc inhibitor:   0.931
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.534
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.439
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.896 Promiscuous compounds:   0.156

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.873 MDCK Permeability:   -4.701
Pgp-inhibitor:   0.594 Pgp-substrate:   0.01
PAMPA:   0.429
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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):   0.005
20% Bioavailability (F20%):   0.216 30% Bioavailability (F30%):   0.005
50% Bioavailability (F50%):   0.495

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.921 MRP1:   0.343
Plasma Protein Binding (PPB):   94.996% Volume Distribution (VD):   -0.177
Fu: 6.031%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.735
OATP1B3 inhibitor:   0.912 BCRP inhibitor:   0.133
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   0.097 CYP1A2-substrate:   0.974
CYP2C19-inhibitor:   0.445 CYP2C19-substrate:   0.549
CYP2C9-inhibitor:   0.899 CYP2C9-substrate:   0.998
CYP2D6-inhibitor:   0.922 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.016 CYP3A4-substrate:   0.968
CYP2B6-substrate:   0.017 CYP2C8-inhibitor:   0.263
HLM stability:   0.148
?
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):  4.387 Half-life (T1/2):  1.192

ADMET: Toxicity

hERG Blockers:  0.17 hERG Blockers (10um):  0.544
Human Hepatotoxicity (H-HT):  0.425 Drug-induced Liver Injury (DILI):  0.316
AMES Toxicity:  0.848 Rat Oral Acute Toxicity:  0.57
Maximum Recommended Daily Dose:  0.196 Skin Sensitization:  0.973
Carcinogencity:  0.742 Eye Corrosion:  0.983
Eye Irritation:  0.992 Respiratory Toxicity:  0.503
Drug-induced Neurotoxicity:  0.823 Ototoxicity:  0.298
Hematotoxicity:  0.169 Drug-induced Nephrotoxicity:  0.586
Genotoxicity:  0.198 RPMI-8226 Immunitoxicity:  0.083
A549 Cytotoxicity:  0.107 Hek293 Cytotoxicity:  0.105
BCF:   1.074
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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:   3.606
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.21
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.69
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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
NPO11460 Sassafras albidum Species Lauraceae Eukaryota n.a. bark n.a. PMID[26411017]
NPO1942 Piper philippinum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[39771253]
NPO11460 Sassafras albidum Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1942 Piper philippinum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO43105 Licaria puchury-major Genus Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26208 Brombya platynema Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28218 Asplenium adiantum-nigrum Species Aspleniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28510 Aspergillus pseudodeflectus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28392 Macrosiphum liriodendri Species Aphididae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11460 Sassafras albidum Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11460 Sassafras albidum Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11460 Sassafras albidum Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26208 Brombya platynema Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1942 Piper philippinum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28510 Aspergillus pseudodeflectus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28392 Macrosiphum liriodendri Species Aphididae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28218 Asplenium adiantum-nigrum Species Aspleniaceae 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

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 NPC539314 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 NPC111225
0.7647 Intermediate Similarity NPC127326
0.6857 Remote Similarity NPC179309
0.65 Remote Similarity NPC212643
0.6098 Remote Similarity NPC57501
0.5909 Remote Similarity NPC199209
0.5778 Remote Similarity NPC217574
0.5652 Remote Similarity NPC167096
0.5652 Remote Similarity NPC605721
0.5532 Remote Similarity NPC470707
0.5417 Remote Similarity NPC300955
0.5417 Remote Similarity NPC469808
0.5417 Remote Similarity NPC469977
0.5306 Remote Similarity NPC94280
0.5306 Remote Similarity NPC296575
0.5294 Remote Similarity NPC471390
0.52 Remote Similarity NPC255817
0.52 Remote Similarity NPC136330
0.5135 Remote Similarity NPC120066
0.5135 Remote Similarity NPC13755
0.5128 Remote Similarity NPC31279
0.5098 Remote Similarity NPC470706
0.5098 Remote Similarity NPC69670

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC539314 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
0.619 Remote Similarity NPD1357 Phase 4
0.52 Remote Similarity NPD2492 Phase 2

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