Natural Product: NPC224227

Natural Product IDNPC224227
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Sodium Linolate
IUPAC Name sodium;(9Z,12Z)-octadeca-9,12-dienoate
Synonyms Sodium Linolate
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL571449
PubChem CID 23676150
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 WYPBVHPKMJYUEO-NBTZWHCOSA-M
Standard InCHI InChI=1S/C18H32O2.Na/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20;/h6-7,9-10H,2-5,8,11-17H2,1H3,(H,19,20);/q;+1/p-1/b7-6-,10-9-;
SMILES CCCCC/C=CC/C=CCCCCCCCC(=O)[O-].[Na+]

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   279.23 Volume:   328.237
?
Van der Waals volume.
Dense:   0.851 LogP:   4.209
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.006
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.149
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   14.0 Rigid Bonds:   3.0
TPSA:   40.13
?
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:   0.346 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.805 Fsp3:   0.722
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:   0.334 Fluc inhibitor:   0.313
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.002
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.019
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.997 Promiscuous compounds:   0.521

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.993 MDCK Permeability:   -4.712
Pgp-inhibitor:   0.064 Pgp-substrate:   0.0
PAMPA:   0.002
?
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):   0.001
20% Bioavailability (F20%):   0.084 30% Bioavailability (F30%):   0.174
50% Bioavailability (F50%):   0.731

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.009 MRP1:   1.0
Plasma Protein Binding (PPB):   98.356% Volume Distribution (VD):   -0.284
Fu: 1.068%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.015
OATP1B3 inhibitor:   0.666 BCRP inhibitor:   0.023
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.125 CYP2C19-substrate:   0.936
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.814 CYP2D6-substrate:   0.873
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.436
?
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):  3.403 Half-life (T1/2):  0.92

ADMET: Toxicity

hERG Blockers:  0.25 hERG Blockers (10um):  0.469
Human Hepatotoxicity (H-HT):  0.325 Drug-induced Liver Injury (DILI):  0.0
AMES Toxicity:  0.131 Rat Oral Acute Toxicity:  0.033
Maximum Recommended Daily Dose:  0.023 Skin Sensitization:  1.0
Carcinogencity:  0.026 Eye Corrosion:  1.0
Eye Irritation:  0.999 Respiratory Toxicity:  0.705
Drug-induced Neurotoxicity:  0.013 Ototoxicity:  0.415
Hematotoxicity:  0.016 Drug-induced Nephrotoxicity:  0.359
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.029
A549 Cytotoxicity:  0.234 Hek293 Cytotoxicity:  0.061
BCF:   1.457
?
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:   4.61
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.818
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.944
?
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
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.carres.2012.01.012]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. PMID[26562741]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. PMID[29517238]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. PMID[31625751]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. Along the Valencian coast, Spain 2020-Jun&Jul PMID[35161358]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota Herb n.a. n.a. Database[FooDB]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. Database[FooDB]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4640 Portulaca oleracea Species Portulacaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]

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
NPT5277 Individual protein Cytochrome P450 1A2 Rattus norvegicus Ki = 13600.0 nM PMID[22331994]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 0.76 ml/cm PMID[17954701]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 1.0 ml PMID[17954701]
NPT2 Others Unspecified n.a. Kd = 130000.0 nM PMID[17954701]

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 NPC224227 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
0.8929 High Similarity NPC262968
0.8667 High Similarity NPC294548
0.7419 Intermediate Similarity NPC184171
0.6786 Remote Similarity NPC67462
0.6786 Remote Similarity NPC156630
0.6286 Remote Similarity NPC154245
0.6286 Remote Similarity NPC85813
0.6286 Remote Similarity NPC223697
0.6286 Remote Similarity NPC6095
0.6 Remote Similarity NPC321062
0.5833 Remote Similarity NPC59051
0.5556 Remote Similarity NPC91495
0.5556 Remote Similarity NPC5413
0.5429 Remote Similarity NPC424
0.5429 Remote Similarity NPC36061
0.5429 Remote Similarity NPC69510
0.5429 Remote Similarity NPC77272
0.5429 Remote Similarity NPC290563
0.5429 Remote Similarity NPC139029
0.5429 Remote Similarity NPC281972
0.5429 Remote Similarity NPC261831
0.5429 Remote Similarity NPC87564
0.5405 Remote Similarity NPC52955
0.5405 Remote Similarity NPC88966
0.5405 Remote Similarity NPC25417
0.5405 Remote Similarity NPC1813
0.5143 Remote Similarity NPC281245
0.5135 Remote Similarity NPC255837
0.5135 Remote Similarity NPC70387
0.5135 Remote Similarity NPC168211

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC224227 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
0.8966 High Similarity NPD3174 Discontinued
0.8929 High Similarity NPD28 Approved
0.8929 High Similarity NPD29 Phase 4
0.6786 Remote Similarity NPD3206 Approved
0.6286 Remote Similarity NPD4266 Phase 2
0.5556 Remote Similarity NPD3173 Phase 4
0.5429 Remote Similarity NPD3195 Phase 2
0.5429 Remote Similarity NPD3196 Approved
0.5405 Remote Similarity NPD3172 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