Natural Product: NPC167759

Natural Product IDNPC167759
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Dodeca-2E,4Z-Diene-8,10-Diynoic Acid Isobutylamide
IUPAC Name (2E,4Z)-N-(2-methylpropyl)dodeca-2,4-dien-8,10-diynamide
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL454195
PubChem CID 11651673
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0000331] Fatty amides
          • [CHEMONTID:0001096] N-acyl amines

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 FOAKNWSNLWCNHO-JPYSRSMKSA-N
Standard InCHI InChI=1S/C16H21NO/c1-4-5-6-7-8-9-10-11-12-13-16(18)17-14-15(2)3/h10-13,15H,8-9,14H2,1-3H3,(H,17,18)/b11-10-,13-12+
SMILES CC#CC#CCC/C=CC=CC(=NCC(C)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   243.16 Volume:   286.624
?
Van der Waals volume.
Dense:   0.848 LogP:   4.127
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.243
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.801
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   5.0
TPSA:   32.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   0.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.25 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.893 Fsp3:   0.438
MCE-18:   0.0
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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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.349 Fluc inhibitor:   0.081
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.003
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.099
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.412 Promiscuous compounds:   0.015

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.309 MDCK Permeability:   -4.632
Pgp-inhibitor:   0.875 Pgp-substrate:   0.0
PAMPA:   0.991
?
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%):   0.003 30% Bioavailability (F30%):   0.008
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.001
Plasma Protein Binding (PPB):   96.636% Volume Distribution (VD):   -0.213
Fu: 2.956%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.015
OATP1B3 inhibitor:   0.075 BCRP inhibitor:   0.992
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.014 CYP1A2-substrate:   0.861
CYP2C19-inhibitor:   0.99 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.036 CYP2C9-substrate:   0.119
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.996
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.182 CYP2C8-inhibitor:   1.0
HLM stability:   0.077
?
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):  8.85 Half-life (T1/2):  0.925

ADMET: Toxicity

hERG Blockers:  0.13 hERG Blockers (10um):  0.384
Human Hepatotoxicity (H-HT):  0.913 Drug-induced Liver Injury (DILI):  0.981
AMES Toxicity:  0.829 Rat Oral Acute Toxicity:  0.608
Maximum Recommended Daily Dose:  0.865 Skin Sensitization:  0.998
Carcinogencity:  0.837 Eye Corrosion:  0.087
Eye Irritation:  0.799 Respiratory Toxicity:  0.997
Drug-induced Neurotoxicity:  0.225 Ototoxicity:  0.646
Hematotoxicity:  0.086 Drug-induced Nephrotoxicity:  0.628
Genotoxicity:  0.452 RPMI-8226 Immunitoxicity:  0.029
A549 Cytotoxicity:  0.015 Hek293 Cytotoxicity:  0.544
BCF:   1.316
?
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:   3.917
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.343
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.746
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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
NPO14484 Echinacea purpurea Species Asteraceae Eukaryota root n.a. n.a. PMID[15921428]
NPO726 Echinacea angustifolia Species Asteraceae Eukaryota root n.a. n.a. PMID[15921428]
NPO14484 Echinacea purpurea Species Asteraceae Eukaryota flowers n.a. n.a. PMID[19374389]
NPO14484 Echinacea purpurea Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[37959750]
NPO726 Echinacea angustifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14484 Echinacea purpurea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14484 Echinacea purpurea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14484 Echinacea purpurea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO726 Echinacea angustifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14484 Echinacea purpurea Species Asteraceae 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
NPT113 Cell line RAW264.7 Mus musculus ID50 = 3.0 ug ml-1 PMID[15921428]

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 NPC167759 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 NPC56028
0.8919 High Similarity NPC123669
0.7561 Intermediate Similarity NPC305288
0.7561 Intermediate Similarity NPC163912
0.6842 Remote Similarity NPC145032
0.6842 Remote Similarity NPC307435
0.6842 Remote Similarity NPC304223
0.6842 Remote Similarity NPC54542
0.6667 Remote Similarity NPC243539
0.6667 Remote Similarity NPC267340
0.65 Remote Similarity NPC195986
0.6341 Remote Similarity NPC104138
0.6341 Remote Similarity NPC273023
0.6341 Remote Similarity NPC24216
0.6341 Remote Similarity NPC306420
0.619 Remote Similarity NPC261158
0.619 Remote Similarity NPC303672
0.6136 Remote Similarity NPC6795
0.6 Remote Similarity NPC267692
0.6 Remote Similarity NPC119655
0.5909 Remote Similarity NPC13011
0.5909 Remote Similarity NPC124382
0.5745 Remote Similarity NPC187315
0.5122 Remote Similarity NPC245650
0.5106 Remote Similarity NPC477049

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC167759 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