Natural Product: NPC491237

Natural Product IDNPC491237
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Stearidonic Acid
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0000504] Lineolic acids and derivatives

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 JIWBIWFOSCKQMA-DFARDDQGSA-N
Standard InCHI InChI=1S/C18H28O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20/h3-4,6-7,9-10,12-13H,2,5,8,11,14-17H2,1H3,(H,19,20)/b4-3+,7-6-,10-9+,13-12+
SMILES CCC=CCC=C/CC=CCC=CCCCCC(O)=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   276.21 Volume:   324.282
?
Van der Waals volume.
Dense:   0.852 LogP:   5.926
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.328
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.481
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   12.0 Rigid Bonds:   5.0
TPSA:   37.3
?
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:   0.381 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.847 Fsp3:   0.5
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:   0.04 Fluc inhibitor:   0.33
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.006
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.008
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.997 Promiscuous compounds:   0.526

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.07 MDCK Permeability:   -4.899
Pgp-inhibitor:   0.011 Pgp-substrate:   0.0
PAMPA:   0.203
?
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%):   0.063 30% Bioavailability (F30%):   0.469
50% Bioavailability (F50%):   0.382

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.723
Plasma Protein Binding (PPB):   99.302% Volume Distribution (VD):   -0.751
Fu: 0.331%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.22
OATP1B3 inhibitor:   0.989 BCRP inhibitor:   0.003
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.003 CYP2C19-substrate:   0.043
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.995 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.0
?
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):  6.491 Half-life (T1/2):  0.308

ADMET: Toxicity

hERG Blockers:  0.032 hERG Blockers (10um):  0.194
Human Hepatotoxicity (H-HT):  0.892 Drug-induced Liver Injury (DILI):  0.175
AMES Toxicity:  0.015 Rat Oral Acute Toxicity:  0.026
Maximum Recommended Daily Dose:  0.345 Skin Sensitization:  0.997
Carcinogencity:  0.2 Eye Corrosion:  0.005
Eye Irritation:  0.823 Respiratory Toxicity:  0.901
Drug-induced Neurotoxicity:  0.112 Ototoxicity:  0.662
Hematotoxicity:  0.203 Drug-induced Nephrotoxicity:  0.191
Genotoxicity:  0.241 RPMI-8226 Immunitoxicity:  0.078
A549 Cytotoxicity:  0.023 Hek293 Cytotoxicity:  0.074
BCF:   1.394
?
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:   4.133
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.523
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.934
?
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
NPO41129 Anarhichas lupus Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO41157 Sebastes alutus Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO41124 Oncorhynchus mykiss Species Salmonidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO41170 Reinhardtius hippoglossoides Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO41170 Reinhardtius hippoglossoides Species n.a. n.a. n.a. n.a. Database[FooDB]
NPO41129 Anarhichas lupus Species n.a. n.a. n.a. n.a. Database[FooDB]
NPO41124 Oncorhynchus mykiss Species Salmonidae Eukaryota n.a. n.a. Database[FooDB]
NPO41157 Sebastes alutus Species n.a. n.a. n.a. n.a. Database[FooDB]
NPO41124 Oncorhynchus mykiss Species Salmonidae Eukaryota n.a. n.a. Database[FooDB]
NPO41129 Anarhichas lupus Species n.a. n.a. n.a. n.a. Database[FooDB]
NPO41157 Sebastes alutus Species n.a. n.a. n.a. n.a. Database[FooDB]
NPO41170 Reinhardtius hippoglossoides Species n.a. n.a. n.a. n.a. Database[FooDB]

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
NPO41124 Oncorhynchus mykiss n.a. n.a. 128 n.a. n.a. mg/100g Database [FooDB]
NPO41129 Anarhichas lupus n.a. n.a. 97 n.a. n.a. mg/100g Database [FooDB]
NPO41157 Sebastes alutus n.a. n.a. 11 n.a. n.a. mg/100g Database [FooDB]
NPO41170 Reinhardtius hippoglossoides n.a. n.a. 307 n.a. n.a. mg/100g Database [FooDB]
NPO41170 Reinhardtius hippoglossoides n.a. n.a. 309 n.a. n.a. mg/100g Database [FooDB]

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 NPC491237 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 NPC149821
0.8966 High Similarity NPC70387
0.8667 High Similarity NPC52955
0.8667 High Similarity NPC88966
0.8667 High Similarity NPC25417
0.8667 High Similarity NPC1813
0.8333 Intermediate Similarity NPC5413
0.8 Intermediate Similarity NPC207292
0.7931 Intermediate Similarity NPC117572
0.7742 Intermediate Similarity NPC321062
0.75 Intermediate Similarity NPC154245
0.75 Intermediate Similarity NPC85813
0.75 Intermediate Similarity NPC223697
0.75 Intermediate Similarity NPC6095
0.7188 Intermediate Similarity NPC91495
0.7097 Intermediate Similarity NPC92114
0.697 Remote Similarity NPC59051
0.6774 Remote Similarity NPC281245
0.6562 Remote Similarity NPC424
0.6562 Remote Similarity NPC36061
0.6562 Remote Similarity NPC69510
0.6562 Remote Similarity NPC77272
0.6562 Remote Similarity NPC290563
0.6562 Remote Similarity NPC139029
0.6562 Remote Similarity NPC281972
0.6562 Remote Similarity NPC261831
0.6562 Remote Similarity NPC87564
0.6216 Remote Similarity NPC284212
0.6129 Remote Similarity NPC270796
0.5882 Remote Similarity NPC95145
0.5882 Remote Similarity NPC325642
0.5882 Remote Similarity NPC65174
0.5714 Remote Similarity NPC48162
0.561 Remote Similarity NPC323597
0.561 Remote Similarity NPC211752
0.561 Remote Similarity NPC323498
0.5517 Remote Similarity NPC175342
0.5476 Remote Similarity NPC317583
0.5385 Remote Similarity NPC323436
0.5385 Remote Similarity NPC327388
0.5385 Remote Similarity NPC606120
0.5357 Remote Similarity NPC134782
0.5357 Remote Similarity NPC268826
0.5349 Remote Similarity NPC320642
0.5349 Remote Similarity NPC329550
0.5333 Remote Similarity NPC155263
0.5278 Remote Similarity NPC294548
0.5227 Remote Similarity NPC323045
0.5227 Remote Similarity NPC317881
0.5172 Remote Similarity NPC214610
0.5172 Remote Similarity NPC118968
0.5172 Remote Similarity NPC183424
0.5172 Remote Similarity NPC294085
0.5161 Remote Similarity NPC171736
0.5161 Remote Similarity NPC301585
0.5161 Remote Similarity NPC261080
0.5161 Remote Similarity NPC132565
0.5161 Remote Similarity NPC209970
0.5161 Remote Similarity NPC216630
0.5161 Remote Similarity NPC201844
0.5161 Remote Similarity NPC301696
0.5161 Remote Similarity NPC196924
0.5161 Remote Similarity NPC307783
0.5161 Remote Similarity NPC154186
0.5161 Remote Similarity NPC149184
0.5161 Remote Similarity NPC279026
0.5161 Remote Similarity NPC113928
0.5161 Remote Similarity NPC14227
0.5152 Remote Similarity NPC180534
0.5152 Remote Similarity NPC611531
0.5128 Remote Similarity NPC477777
0.5122 Remote Similarity NPC477201
0.5116 Remote Similarity NPC320305
0.5116 Remote Similarity NPC321838
0.5111 Remote Similarity NPC322461
0.5102 Remote Similarity NPC610068

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC491237 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
0.8667 High Similarity NPD3172 Approved
0.8333 Intermediate Similarity NPD3173 Phase 4
0.7931 Intermediate Similarity NPD4222 Phase 3
0.75 Intermediate Similarity NPD4266 Phase 2
0.7105 Intermediate Similarity NPD39 Phase 4
0.6562 Remote Similarity NPD3195 Phase 2
0.6562 Remote Similarity NPD3196 Approved
0.6129 Remote Similarity NPD5326 Phase 3
0.5385 Remote Similarity NPD3194 Phase 4
0.5172 Remote Similarity NPD9655 Phase 4
0.5161 Remote Similarity NPD2270 Pre-clinical
0.5161 Remote Similarity NPD633 Phase 3
0.5161 Remote Similarity NPD9448 Phase 2
0.5152 Remote Similarity NPD622 Pre-clinical

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