Natural Product: NPC469786

Natural Product IDNPC469786
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 N-[2-(1H-Indol-3-Yl)Ethyl]Tridecanamide
IUPAC Name N-[2-(1H-indol-3-yl)ethyl]tridecanamide
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1171805
PubChem CID 22216891
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0002497] Indoles
          • [CHEMONTID:0004196] 3-alkylindoles

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 LNHZLMYNAZPRES-UHFFFAOYSA-N
Standard InCHI InChI=1S/C23H36N2O/c1-2-3-4-5-6-7-8-9-10-11-16-23(26)24-18-17-20-19-25-22-15-13-12-14-21(20)22/h12-15,19,25H,2-11,16-18H2,1H3,(H,24,26)
SMILES CCCCCCCCCCCCC(=O)NCCC1=CNC2=CC=CC=C21

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.28 Volume:   406.853
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Van der Waals volume.
Dense:   0.876 LogP:   6.058
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.332
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.734
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The logarithm of aqueous solubility value.
Rotatable Bonds:   15.0 Rigid Bonds:   11.0
TPSA:   44.89
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.392 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.973 Fsp3:   0.609
MCE-18:   10.0
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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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.746 Fluc inhibitor:   0.002
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.033
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.512
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.001 Promiscuous compounds:   0.123

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.112 MDCK Permeability:   -4.813
Pgp-inhibitor:   0.06 Pgp-substrate:   0.854
PAMPA:   0.016
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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):   0.746
20% Bioavailability (F20%):   0.598 30% Bioavailability (F30%):   0.874
50% Bioavailability (F50%):   0.936

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.309 MRP1:   0.515
Plasma Protein Binding (PPB):   98.832% Volume Distribution (VD):   0.481
Fu: 0.884%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.267
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.33
BSEP inhibitor:   0.975

ADMET: Metabolism

CYP1A2-inhibitor:   0.006 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.994 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.861
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.039 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.087 CYP2C8-inhibitor:   1.0
HLM stability:   0.999
?
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):  5.704 Half-life (T1/2):  0.309

ADMET: Toxicity

hERG Blockers:  0.619 hERG Blockers (10um):  0.843
Human Hepatotoxicity (H-HT):  0.571 Drug-induced Liver Injury (DILI):  0.147
AMES Toxicity:  0.176 Rat Oral Acute Toxicity:  0.281
Maximum Recommended Daily Dose:  0.514 Skin Sensitization:  0.923
Carcinogencity:  0.283 Eye Corrosion:  0.019
Eye Irritation:  0.864 Respiratory Toxicity:  0.928
Drug-induced Neurotoxicity:  0.258 Ototoxicity:  0.373
Hematotoxicity:  0.175 Drug-induced Nephrotoxicity:  0.237
Genotoxicity:  0.001 RPMI-8226 Immunitoxicity:  0.039
A549 Cytotoxicity:  0.422 Hek293 Cytotoxicity:  0.184
BCF:   1.429
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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:   4.701
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.98
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.951
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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
NPO31161 Annonaceae Genus Annonaceae Eukaryota n.a. n.a. n.a. PMID[20579892]
NPO31161 Annonaceae Genus Annonaceae Eukaryota n.a. leaf n.a. PMID[23513739]
NPO31161 Annonaceae Genus Annonaceae Eukaryota n.a. fruit n.a. PMID[26920282]
NPO31161 Annonaceae Genus Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT4564 Cell line Neurons n.a. Activity = 98.5 % PMID[21807509]
NPT4564 Cell line Neurons n.a. Activity = 126.2 % PMID[12762819]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 1000000.0 nM PMID[20579892]

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 NPC469786 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 NPC469760
0.8235 Intermediate Similarity NPC608269
0.8214 Intermediate Similarity NPC469762
0.678 Remote Similarity NPC605381
0.6441 Remote Similarity NPC476460
0.5968 Remote Similarity NPC259644
0.5968 Remote Similarity NPC70922
0.5968 Remote Similarity NPC211572
0.5968 Remote Similarity NPC75540
0.5968 Remote Similarity NPC212376
0.5968 Remote Similarity NPC469765
0.5968 Remote Similarity NPC80597
0.5968 Remote Similarity NPC25008
0.5968 Remote Similarity NPC73952
0.5357 Remote Similarity NPC310665
0.5246 Remote Similarity NPC602373
0.5211 Remote Similarity NPC469763
0.5161 Remote Similarity NPC314002
0.5161 Remote Similarity NPC606242
0.5152 Remote Similarity NPC611116
0.5147 Remote Similarity NPC105818
0.5085 Remote Similarity NPC600736
0.5079 Remote Similarity NPC469780
0.5079 Remote Similarity NPC469761
0.5079 Remote Similarity NPC469783
0.5079 Remote Similarity NPC469766
0.5079 Remote Similarity NPC469779
0.5079 Remote Similarity NPC469768
0.5079 Remote Similarity NPC469784
0.5079 Remote Similarity NPC602670

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC469786 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