Natural Product: NPC476655

Natural Product IDNPC476655
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2,3-dihydroxypropyl (5E,7E)-nonadeca-5,7-dienoate
IUPAC Name 2,3-dihydroxypropyl (5E,7E)-nonadeca-5,7-dienoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 76320328
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000175] Glycerolipids
        • [CHEMONTID:0003808] Monoradylglycerols
          • [CHEMONTID:0001133] Monoacylglycerols
            • [CHEMONTID:0001597] 1-monoacylglycerols

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 CEPAYHKRLMYIBN-SQIWNDBBSA-N
Standard InCHI InChI=1S/C22H40O4/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-22(25)26-20-21(24)19-23/h12-15,21,23-24H,2-11,16-20H2,1H3/b13-12+,15-14+
SMILES CCCCCCCCCCC/C=C/C=C/CCCC(=O)OCC(CO)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   368.29 Volume:   416.32
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Van der Waals volume.
Dense:   0.885 LogP:   4.766
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.728
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.338
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The logarithm of aqueous solubility value.
Rotatable Bonds:   19.0 Rigid Bonds:   3.0
TPSA:   66.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   0.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.201 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.984 Fsp3:   0.773
MCE-18:   2.0
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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:   0.405 Fluc inhibitor:   0.0
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.003
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.01
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.888 Promiscuous compounds:   0.209

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.072 MDCK Permeability:   -4.701
Pgp-inhibitor:   0.0 Pgp-substrate:   0.461
PAMPA:   0.02
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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):   0.146
20% Bioavailability (F20%):   0.978 30% Bioavailability (F30%):   0.997
50% Bioavailability (F50%):   0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.444
Plasma Protein Binding (PPB):   98.098% Volume Distribution (VD):   -0.303
Fu: 0.994%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.035
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.547
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   0.759
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.004
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   0.241
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.605
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.117
?
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):  4.909 Half-life (T1/2):  0.665

ADMET: Toxicity

hERG Blockers:  0.231 hERG Blockers (10um):  0.576
Human Hepatotoxicity (H-HT):  0.351 Drug-induced Liver Injury (DILI):  0.017
AMES Toxicity:  0.495 Rat Oral Acute Toxicity:  0.018
Maximum Recommended Daily Dose:  0.109 Skin Sensitization:  0.996
Carcinogencity:  0.263 Eye Corrosion:  0.049
Eye Irritation:  0.737 Respiratory Toxicity:  0.099
Drug-induced Neurotoxicity:  0.026 Ototoxicity:  0.793
Hematotoxicity:  0.08 Drug-induced Nephrotoxicity:  0.539
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.033
A549 Cytotoxicity:  0.125 Hek293 Cytotoxicity:  0.114
BCF:   1.281
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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:   4.974
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.346
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.453
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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
NPO33615 Aspergillus sp. MF-93 Species Aspergillaceae Eukaryota n.a. Quan-Zhou Gulf, Fujian Province, China 2002 PMID[18823067]
NPO33615 Aspergillus sp. MF-93 Species Aspergillaceae 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
NPT786 Organism Tobacco mosaic virus Tobacco mosaic virus Inhibition = 14.9 % PMID[18823067]

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 NPC476655 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 NPC476654
1.0 High Similarity NPC476656
0.8333 Intermediate Similarity NPC104537
0.7895 Intermediate Similarity NPC321919
0.7692 Intermediate Similarity NPC330426
0.7692 Intermediate Similarity NPC127091
0.7692 Intermediate Similarity NPC22101
0.75 Intermediate Similarity NPC474321
0.725 Intermediate Similarity NPC209327
0.7143 Intermediate Similarity NPC488257
0.7143 Intermediate Similarity NPC469937
0.7143 Intermediate Similarity NPC94699
0.7143 Intermediate Similarity NPC320588
0.7143 Intermediate Similarity NPC53463
0.7073 Intermediate Similarity NPC273508
0.6829 Remote Similarity NPC271921
0.6667 Remote Similarity NPC277597
0.6341 Remote Similarity NPC476657
0.6341 Remote Similarity NPC476659
0.619 Remote Similarity NPC475443
0.619 Remote Similarity NPC473829
0.5952 Remote Similarity NPC476660
0.5789 Remote Similarity NPC128061
0.5789 Remote Similarity NPC228473
0.5778 Remote Similarity NPC48218
0.5778 Remote Similarity NPC141481
0.5778 Remote Similarity NPC464342
0.575 Remote Similarity NPC609455
0.5714 Remote Similarity NPC485026
0.5652 Remote Similarity NPC473772
0.5455 Remote Similarity NPC476658
0.5417 Remote Similarity NPC473559
0.5417 Remote Similarity NPC324981
0.5366 Remote Similarity NPC223677
0.5366 Remote Similarity NPC28779
0.5128 Remote Similarity NPC26253
0.5116 Remote Similarity NPC148192

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC476655 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
0.5556 Remote Similarity NPD3728 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