Natural Product: NPC301713

Natural Product IDNPC301713
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 N-(3,4-Dimethoxyphenethyl)Cinnamamide
IUPAC Name (E)-N-[2-(3,4-dimethoxyphenyl)ethyl]-3-phenylprop-2-enamide
Synonyms N-(3,4-Dimethoxyphenethyl)Cinnamamide
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL252000
PubChem CID 1376042
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000476] Cinnamic acids and derivatives
        • [CHEMONTID:0002810] Cinnamic acid amides

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 YMZWKEYJSYDVKL-PKNBQFBNSA-N
Standard InCHI InChI=1S/C19H21NO3/c1-22-17-10-8-16(14-18(17)23-2)12-13-20-19(21)11-9-15-6-4-3-5-7-15/h3-11,14H,12-13H2,1-2H3,(H,20,21)/b11-9+
SMILES COc1ccc(CCN=C(/C=C/c2ccccc2)O)cc1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   311.15 Volume:   336.343
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Van der Waals volume.
Dense:   0.925 LogP:   3.126
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.955
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.65
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   14.0
TPSA:   51.05
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.623 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.255 Fsp3:   0.211
MCE-18:   11.0
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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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.988 Fluc inhibitor:   0.999
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.127
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.908
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.013 Promiscuous compounds:   0.234

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.67 MDCK Permeability:   -4.611
Pgp-inhibitor:   0.632 Pgp-substrate:   0.338
PAMPA:   0.052
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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):   0.028
20% Bioavailability (F20%):   0.681 30% Bioavailability (F30%):   0.726
50% Bioavailability (F50%):   0.981

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.032
Plasma Protein Binding (PPB):   98.701% Volume Distribution (VD):   0.002
Fu: 0.864%
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The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.985
OATP1B3 inhibitor:   0.833 BCRP inhibitor:   0.018
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.149 CYP1A2-substrate:   0.993
CYP2C19-inhibitor:   0.738 CYP2C19-substrate:   0.776
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.185
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.758
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.159
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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):  8.41 Half-life (T1/2):  0.842

ADMET: Toxicity

hERG Blockers:  0.366 hERG Blockers (10um):  0.439
Human Hepatotoxicity (H-HT):  0.903 Drug-induced Liver Injury (DILI):  0.79
AMES Toxicity:  0.662 Rat Oral Acute Toxicity:  0.42
Maximum Recommended Daily Dose:  0.541 Skin Sensitization:  0.979
Carcinogencity:  0.517 Eye Corrosion:  0.002
Eye Irritation:  0.59 Respiratory Toxicity:  0.85
Drug-induced Neurotoxicity:  0.488 Ototoxicity:  0.516
Hematotoxicity:  0.302 Drug-induced Nephrotoxicity:  0.667
Genotoxicity:  0.23 RPMI-8226 Immunitoxicity:  0.023
A549 Cytotoxicity:  0.103 Hek293 Cytotoxicity:  0.303
BCF:   0.902
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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:   3.563
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.696
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.225
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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
NPO24692 Zanthoxylum sp. Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24692 Zanthoxylum sp. Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]

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
NPT32 Organism Mus musculus Mus musculus Activity = 6.7 % PMID[18353644]
NPT32 Organism Mus musculus Mus musculus Activity = 3.26 % PMID[18353644]
NPT29 Organism Rattus norvegicus Rattus norvegicus Activity = 20.1 % PMID[18353644]





 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 NPC301713 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
0.6875 Remote Similarity NPC203076
0.6491 Remote Similarity NPC263835
0.614 Remote Similarity NPC251571
0.6111 Remote Similarity NPC96224
0.6102 Remote Similarity NPC155838
0.5763 Remote Similarity NPC214869
0.5714 Remote Similarity NPC182119
0.5536 Remote Similarity NPC283468
0.55 Remote Similarity NPC61879
0.55 Remote Similarity NPC296898
0.5424 Remote Similarity NPC211218
0.5424 Remote Similarity NPC62101
0.5424 Remote Similarity NPC95733
0.5323 Remote Similarity NPC52029
0.5323 Remote Similarity NPC178571
0.5323 Remote Similarity NPC195749
0.5323 Remote Similarity NPC35961
0.5273 Remote Similarity NPC24101
0.5263 Remote Similarity NPC303370

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC301713 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
0.5075 Remote Similarity NPD4083 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