Natural Product: NPC596498

Natural Product IDNPC596498
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7,10,13-HEXADECATRIENOIC ACID METHYL ESTER
IUPAC Name methyl hexadeca-7,10,13-trienoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 DUOCBVNCDAEWTB-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H28O2/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17(18)19-2/h4-5,7-8,10-11H,3,6,9,12-16H2,1-2H3
SMILES CCC=CCC=CCC=CCCCCCC(=O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   264.21 Volume:   309.623
?
Van der Waals volume.
Dense:   0.853 LogP:   5.556
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.552
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.084
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   12.0 Rigid Bonds:   4.0
TPSA:   26.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   0.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.299 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.63 Fsp3:   0.588
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.043 Fluc inhibitor:   0.32
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.005
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.016
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.998 Promiscuous compounds:   0.341

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.958 MDCK Permeability:   -4.733
Pgp-inhibitor:   0.676 Pgp-substrate:   0.055
PAMPA:   0.012
?
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):   0.012
20% Bioavailability (F20%):   0.176 30% Bioavailability (F30%):   0.49
50% Bioavailability (F50%):   0.706

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.232 MRP1:   0.984
Plasma Protein Binding (PPB):   97.314% Volume Distribution (VD):   -0.448
Fu: 3.164%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.089
OATP1B3 inhibitor:   0.473 BCRP inhibitor:   0.429
BSEP inhibitor:   0.992

ADMET: Metabolism

CYP1A2-inhibitor:   0.055 CYP1A2-substrate:   0.993
CYP2C19-inhibitor:   0.589 CYP2C19-substrate:   0.21
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.991
?
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):  6.619 Half-life (T1/2):  0.199

ADMET: Toxicity

hERG Blockers:  0.135 hERG Blockers (10um):  0.398
Human Hepatotoxicity (H-HT):  0.101 Drug-induced Liver Injury (DILI):  0.005
AMES Toxicity:  0.603 Rat Oral Acute Toxicity:  0.116
Maximum Recommended Daily Dose:  0.116 Skin Sensitization:  0.999
Carcinogencity:  0.45 Eye Corrosion:  0.988
Eye Irritation:  0.996 Respiratory Toxicity:  0.763
Drug-induced Neurotoxicity:  0.098 Ototoxicity:  0.206
Hematotoxicity:  0.03 Drug-induced Nephrotoxicity:  0.255
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.027
A549 Cytotoxicity:  0.015 Hek293 Cytotoxicity:  0.017
BCF:   1.916
?
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:   4.49
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.789
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.168
?
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
NPO22234 Ficus carica Species Moraceae Eukaryota n.a. n.a. n.a. PMID[11473446]
NPO6065 Brassica carinata Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[36599374]
NPO22234 Ficus carica Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6065 Brassica carinata Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22234 Ficus carica Species Moraceae Eukaryota n.a. n.a. Database[FooDB]
NPO22234 Ficus carica Species Moraceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO22234 Ficus carica Species Moraceae Eukaryota Latex Exudate n.a. n.a. Database[FooDB]
NPO22234 Ficus carica Species Moraceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO22234 Ficus carica Species Moraceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO22234 Ficus carica Species Moraceae Eukaryota Fruits n.a. Database[FooDB]
NPO22234 Ficus carica Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22234 Ficus carica Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22234 Ficus carica Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO6065 Brassica carinata Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22234 Ficus carica Species Moraceae 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
NPO6065 Brassica carinata n.a. n.a. 2.22 n.a. n.a. % PMID[36599374]

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 NPC596498 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 NPC139545
0.8621 High Similarity NPC39633
0.7586 Intermediate Similarity NPC309606
0.75 Intermediate Similarity NPC10316
0.75 Intermediate Similarity NPC200845
0.6562 Remote Similarity NPC228473
0.6471 Remote Similarity NPC28779
0.6316 Remote Similarity NPC271921
0.6 Remote Similarity NPC216130
0.5854 Remote Similarity NPC473772
0.5641 Remote Similarity NPC475443
0.5641 Remote Similarity NPC473829
0.5588 Remote Similarity NPC128061
0.5556 Remote Similarity NPC219536
0.5556 Remote Similarity NPC31551
0.5517 Remote Similarity NPC201622
0.5517 Remote Similarity NPC305660
0.5517 Remote Similarity NPC161097
0.5517 Remote Similarity NPC28598
0.5517 Remote Similarity NPC22903
0.5517 Remote Similarity NPC54980
0.55 Remote Similarity NPC330426
0.55 Remote Similarity NPC127091
0.55 Remote Similarity NPC22101
0.5366 Remote Similarity NPC54925
0.5185 Remote Similarity NPC57499
0.5135 Remote Similarity NPC223677

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC596498 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
0.6364 Remote Similarity NPD5343 Phase 4
0.6 Remote Similarity NPD6096 Phase 4
0.5294 Remote Similarity NPD6097 Approved

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