Natural Product: NPC277333

Natural Product IDNPC277333
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Tetradecanamide
IUPAC Name tetradecanamide
Synonyms Tetradecanamide; Tetradecanoic Acid Amide
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL88158
PubChem CID 69492
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0000331] Fatty 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 QEALYLRSRQDCRA-UHFFFAOYSA-N
Standard InCHI InChI=1S/C14H29NO/c1-2-3-4-5-6-7-8-9-10-11-12-13-14(15)16/h2-13H2,1H3,(H2,15,16)
SMILES CCCCCCCCCCCCCC(=N)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   227.22 Volume:   267.851
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Van der Waals volume.
Dense:   0.848 LogP:   4.692
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.225
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.856
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The logarithm of aqueous solubility value.
Rotatable Bonds:   12.0 Rigid Bonds:   1.0
TPSA:   44.08
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Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   0.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.268 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.135 Fsp3:   0.929
MCE-18:   0.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.621 Fluc inhibitor:   0.009
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.002
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.019
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.747 Promiscuous compounds:   0.258

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.258 MDCK Permeability:   -4.819
Pgp-inhibitor:   0.002 Pgp-substrate:   0.388
PAMPA:   0.11
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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):   0.848
20% Bioavailability (F20%):   0.919 30% Bioavailability (F30%):   0.951
50% Bioavailability (F50%):   0.531

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.023 MRP1:   0.895
Plasma Protein Binding (PPB):   98.001% Volume Distribution (VD):   1.006
Fu: 3.298%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.312
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.471
BSEP inhibitor:   0.131

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.019
CYP2D6-inhibitor:   0.926 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.126 CYP3A4-substrate:   0.383
CYP2B6-substrate:   0.008 CYP2C8-inhibitor:   0.424
HLM stability:   0.015
?
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):  4.769 Half-life (T1/2):  0.577

ADMET: Toxicity

hERG Blockers:  0.176 hERG Blockers (10um):  0.497
Human Hepatotoxicity (H-HT):  0.94 Drug-induced Liver Injury (DILI):  0.277
AMES Toxicity:  0.105 Rat Oral Acute Toxicity:  0.252
Maximum Recommended Daily Dose:  0.08 Skin Sensitization:  0.999
Carcinogencity:  0.787 Eye Corrosion:  0.406
Eye Irritation:  0.988 Respiratory Toxicity:  0.985
Drug-induced Neurotoxicity:  0.126 Ototoxicity:  0.217
Hematotoxicity:  0.142 Drug-induced Nephrotoxicity:  0.254
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.012
A549 Cytotoxicity:  0.373 Hek293 Cytotoxicity:  0.098
BCF:   1.271
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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:   4.346
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.59
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.167
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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
NPO9927.2 Crinum asiaticum var. sinicum Varieties Amaryllidaceae Eukaryota n.a. bulb n.a. PMID[21314165]
NPO9927.2 Crinum asiaticum var. sinicum Varieties Amaryllidaceae Eukaryota n.a. leaf n.a. PMID[21314165]
NPO54179 Magnolia sumatrana var. glauca Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[34328033]
NPO55679 Lagerstroemia Thorelli Genus Lythraceae Eukaryota n.a. n.a. n.a. PMID[39212321]
NPO9927.2 Crinum asiaticum var. sinicum Varieties Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9927.2 Crinum asiaticum var. sinicum Varieties Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9927.2 Crinum asiaticum var. sinicum Varieties Amaryllidaceae 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
NPO54179 Magnolia sumatrana var. glauca Oil Leaves 0.34 n.a. n.a. % PMID[34328033]
NPO55679 Lagerstroemia Thorelli n.a. n.a. 0.85 n.a. n.a. % PMID[39212321]

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
NPT1260 Individual protein Anandamide amidohydrolase Rattus norvegicus Relative rate of hydrolysis = 0.83 n.a. PMID[11128635]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT729 Organism Micrococcus luteus Micrococcus luteus MIC = 5128613.84 nM PMID[16554156]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 2570395.78 nM PMID[16554156]
NPT19 Organism Escherichia coli Escherichia coli MIC = 3090295.43 nM PMID[16554156]

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 NPC277333 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 NPC28394
1.0 High Similarity NPC31557
0.7273 Intermediate Similarity NPC261571
0.7273 Intermediate Similarity NPC188341
0.64 Remote Similarity NPC49494

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC277333 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