Natural Product: NPC226592

Natural Product IDNPC226592
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (S)-17-Hydroxy-15E-Octadecen-9,11,13-Triynoic Acid
IUPAC Name (E,17S)-17-hydroxyoctadec-15-en-9,11,13-triynoic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL459819
PubChem CID 10016854
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0000262] Fatty acids and conjugates
          • [CHEMONTID:0002949] Long-chain fatty acids

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 UQORHUYKZNBNLF-VOGRQWBCSA-N
Standard InCHI InChI=1S/C18H22O3/c1-17(19)15-13-11-9-7-5-3-2-4-6-8-10-12-14-16-18(20)21/h13,15,17,19H,4,6,8,10,12,14,16H2,1H3,(H,20,21)/b15-13+/t17-/m0/s1
SMILES C[C@@H](/C=C/C#CC#CC#CCCCCCCCC(=O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   286.16 Volume:   325.163
?
Van der Waals volume.
Dense:   0.88 LogP:   3.75
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.732
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.413
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   5.0
TPSA:   57.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   0.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.533 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.669 Fsp3:   0.5
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.007 Fluc inhibitor:   0.267
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.042
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.158
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.64 Promiscuous compounds:   0.193

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.833 MDCK Permeability:   -4.629
Pgp-inhibitor:   0.001 Pgp-substrate:   0.0
PAMPA:   1.0
?
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):   0.008
20% Bioavailability (F20%):   0.005 30% Bioavailability (F30%):   0.003
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.0
Plasma Protein Binding (PPB):   98.192% Volume Distribution (VD):   -0.036
Fu: 0.681%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.0
OATP1B3 inhibitor:   0.029 BCRP inhibitor:   0.998
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.969
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.279 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.858
CYP2B6-substrate:   0.001 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):  2.933 Half-life (T1/2):  1.291

ADMET: Toxicity

hERG Blockers:  0.04 hERG Blockers (10um):  0.164
Human Hepatotoxicity (H-HT):  0.682 Drug-induced Liver Injury (DILI):  0.656
AMES Toxicity:  0.305 Rat Oral Acute Toxicity:  0.349
Maximum Recommended Daily Dose:  0.652 Skin Sensitization:  0.942
Carcinogencity:  0.401 Eye Corrosion:  0.885
Eye Irritation:  0.988 Respiratory Toxicity:  0.986
Drug-induced Neurotoxicity:  0.156 Ototoxicity:  0.546
Hematotoxicity:  0.224 Drug-induced Nephrotoxicity:  0.335
Genotoxicity:  0.005 RPMI-8226 Immunitoxicity:  0.06
A549 Cytotoxicity:  0.022 Hek293 Cytotoxicity:  0.074
BCF:   1.25
?
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:   4.107
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.364
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.019
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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
NPO32829 ochanostachys amentacea Species Coulaceae Eukaryota twigs n.a. n.a. PMID[11430012]

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
NPT1034 Cell line Lu1 Homo sapiens ED50 > 20.0 ug ml-1 PMID[18537291]
NPT1851 Cell line Col2 Homo sapiens ED50 = 9.9 ug ml-1 PMID[17958396]
NPT91 Cell line KB Homo sapiens ED50 = 1.1 ug ml-1 PMID[22578169]
NPT91 Cell line KB Homo sapiens ED50 > 20.0 ug ml-1 PMID[20516271]
NPT858 Cell line LNCaP Homo sapiens ED50 = 0.3 ug ml-1 PMID[20516271]
NPT2345 Cell line SW626 Homo sapiens ED50 = 0.36 ug ml-1 PMID[26264503]
NPT136 Cell line SK-N-SH Homo sapiens ED50 = 3.7 ug ml-1 PMID[19596885]
NPT726 Cell line M109 Mus musculus ED50 = 5.4 ug ml-1 PMID[25211145]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. ED50 > 20.0 ug ml-1 PMID[11430012]

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 NPC226592 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
0.6977 Remote Similarity NPC304162
0.6889 Remote Similarity NPC187777
0.6667 Remote Similarity NPC274290
0.6383 Remote Similarity NPC54766
0.6304 Remote Similarity NPC100096
0.6136 Remote Similarity NPC18357
0.6087 Remote Similarity NPC28205
0.5714 Remote Similarity NPC73245
0.5476 Remote Similarity NPC8219
0.5306 Remote Similarity NPC179764
0.5294 Remote Similarity NPC470320
0.52 Remote Similarity NPC473863
0.5192 Remote Similarity NPC470410
0.5192 Remote Similarity NPC470412
0.5116 Remote Similarity NPC129972
0.5116 Remote Similarity NPC301528
0.5116 Remote Similarity NPC71317
0.5116 Remote Similarity NPC163746
0.5116 Remote Similarity NPC103286

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC226592 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