Natural Product: NPC251042

Natural Product IDNPC251042
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (10E,12E)-9-Oxooctadeca-10,12-Dienoic Acid
IUPAC Name (10E,12E)-9-oxooctadeca-10,12-dienoic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL465240
PubChem CID 5283011
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 LUZSWWYKKLTDHU-SIGMCMEVSA-N
Standard InCHI InChI=1S/C18H30O3/c1-2-3-4-5-6-8-11-14-17(19)15-12-9-7-10-13-16-18(20)21/h6,8,11,14H,2-5,7,9-10,12-13,15-16H2,1H3,(H,20,21)/b8-6+,14-11+
SMILES CCCCC/C=C/C=C/C(=O)CCCCCCCC(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   294.22 Volume:   335.709
?
Van der Waals volume.
Dense:   0.876 LogP:   4.277
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.958
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.738
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   14.0 Rigid Bonds:   4.0
TPSA:   54.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   0.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.277 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.399 Fsp3:   0.667
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.156 Fluc inhibitor:   0.287
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.007
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.109
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.991 Promiscuous compounds:   0.732

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.112 MDCK Permeability:   -4.728
Pgp-inhibitor:   0.001 Pgp-substrate:   0.015
PAMPA:   0.692
?
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):   0.015
20% Bioavailability (F20%):   0.041 30% Bioavailability (F30%):   0.301
50% Bioavailability (F50%):   0.289

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.853
Plasma Protein Binding (PPB):   96.333% Volume Distribution (VD):   -0.423
Fu: 3.648%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.162
OATP1B3 inhibitor:   0.985 BCRP inhibitor:   0.006
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.975
CYP2C19-inhibitor:   0.005 CYP2C19-substrate:   0.987
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.583
CYP2D6-inhibitor:   0.093 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.982 CYP2C8-inhibitor:   1.0
HLM stability:   0.035
?
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):  3.56 Half-life (T1/2):  0.883

ADMET: Toxicity

hERG Blockers:  0.144 hERG Blockers (10um):  0.214
Human Hepatotoxicity (H-HT):  0.597 Drug-induced Liver Injury (DILI):  0.308
AMES Toxicity:  0.207 Rat Oral Acute Toxicity:  0.087
Maximum Recommended Daily Dose:  0.355 Skin Sensitization:  0.896
Carcinogencity:  0.185 Eye Corrosion:  0.71
Eye Irritation:  0.989 Respiratory Toxicity:  0.823
Drug-induced Neurotoxicity:  0.087 Ototoxicity:  0.382
Hematotoxicity:  0.284 Drug-induced Nephrotoxicity:  0.551
Genotoxicity:  0.001 RPMI-8226 Immunitoxicity:  0.05
A549 Cytotoxicity:  0.024 Hek293 Cytotoxicity:  0.095
BCF:   1.241
?
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:   4.206
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.555
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.689
?
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
NPO33018 clitocybe clavipes Species Tricholomataceae Eukaryota n.a. n.a. n.a. PMID[12444711]
NPO32691 gomphus floccosus Species n.a. n.a. n.a. n.a. n.a. PMID[18557621]

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
NPT6555 Individual protein Aldehyde dehydrogenase 1, mitochondrial Saccharomyces cerevisiae Inhibition < 50.0 % PMID[21456549]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT635 Organism Botryotinia fuckeliana Botryotinia fuckeliana IC50 > 333000.0 nM PMID[15332848]
NPT635 Organism Botryotinia fuckeliana Botryotinia fuckeliana IC50 = 90000.0 nM PMID[26331334]
NPT637 Organism Fusarium oxysporum Fusarium oxysporum IC50 > 333000.0 nM Open TG-GATES in vivo data: Biochemistry
NPT851 Organism Colletotrichum fragariae Colletotrichum fragariae IC50 > 333000.0 nM PMID[25894905]
NPT851 Organism Colletotrichum fragariae Colletotrichum fragariae IZ = 4.0 mm PMID[10479318]
NPT851 Organism Colletotrichum fragariae Colletotrichum fragariae IZ = 6.0 mm PMID[24328302]
NPT852 Organism Phomopsis obscurans Phomopsis obscurans IC50 = 23000.0 nM DOI[10.1007/s00044-007-9020-0]
NPT851 Organism Colletotrichum fragariae Colletotrichum fragariae IC50 = 91000.0 nM PMID[10843598]
NPT562 Organism Colletotrichum gloeosporioides Colletotrichum gloeosporioides IC50 > 333000.0 nM PMID[16643040]
NPT2241 Organism Glomerella acutata Glomerella acutata IC50 > 333000.0 nM PMID[15341957]
NPT562 Organism Colletotrichum gloeosporioides Colletotrichum gloeosporioides IZ = 6.0 mm PMID[22568524]
NPT562 Organism Colletotrichum gloeosporioides Colletotrichum gloeosporioides IZ = 7.0 mm PMID[15921425]
NPT2241 Organism Glomerella acutata Glomerella acutata IZ = 8.0 mm PMID[24328302]
NPT2241 Organism Glomerella acutata Glomerella acutata IZ = 17.0 mm PMID[24210499]
NPT1095 Organism Plasmopara viticola Plasmopara viticola IC50 = 110000.0 nM PMID[24210499]
NPT1095 Organism Plasmopara viticola Plasmopara viticola IC50 = 65000.0 nM PubChem BioAssay data set

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 NPC251042 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 NPC174447
1.0 High Similarity NPC122521
0.8462 Intermediate Similarity NPC106851
0.8462 Intermediate Similarity NPC282788
0.8462 Intermediate Similarity NPC274927
0.8378 Intermediate Similarity NPC40082
0.7297 Intermediate Similarity NPC95145
0.7297 Intermediate Similarity NPC325642
0.7297 Intermediate Similarity NPC65174
0.7273 Intermediate Similarity NPC325977
0.7273 Intermediate Similarity NPC329550
0.7143 Intermediate Similarity NPC477201
0.6579 Remote Similarity NPC424
0.6579 Remote Similarity NPC36061
0.6579 Remote Similarity NPC69510
0.6579 Remote Similarity NPC77272
0.6579 Remote Similarity NPC290563
0.6579 Remote Similarity NPC139029
0.6579 Remote Similarity NPC281972
0.6579 Remote Similarity NPC261831
0.6579 Remote Similarity NPC87564
0.6522 Remote Similarity NPC235242
0.641 Remote Similarity NPC18712
0.641 Remote Similarity NPC74845
0.6316 Remote Similarity NPC281245
0.625 Remote Similarity NPC322461
0.617 Remote Similarity NPC143396
0.6154 Remote Similarity NPC92114
0.6098 Remote Similarity NPC154245
0.6098 Remote Similarity NPC85813
0.6098 Remote Similarity NPC223697
0.6098 Remote Similarity NPC6095
0.5854 Remote Similarity NPC321062
0.5778 Remote Similarity NPC482480
0.5778 Remote Similarity NPC482481
0.5745 Remote Similarity NPC255863
0.5745 Remote Similarity NPC136164
0.5745 Remote Similarity NPC245947
0.5625 Remote Similarity NPC318420
0.5625 Remote Similarity NPC326268
0.5476 Remote Similarity NPC5413
0.5417 Remote Similarity NPC243532
0.5405 Remote Similarity NPC171736
0.5405 Remote Similarity NPC301585
0.5405 Remote Similarity NPC261080
0.5405 Remote Similarity NPC132565
0.5405 Remote Similarity NPC209970
0.5405 Remote Similarity NPC216630
0.5405 Remote Similarity NPC201844
0.5405 Remote Similarity NPC301696
0.5405 Remote Similarity NPC196924
0.5405 Remote Similarity NPC307783
0.5405 Remote Similarity NPC154186
0.5405 Remote Similarity NPC149184
0.5405 Remote Similarity NPC279026
0.5405 Remote Similarity NPC113928
0.5405 Remote Similarity NPC14227
0.5349 Remote Similarity NPC52955
0.5349 Remote Similarity NPC88966
0.5349 Remote Similarity NPC25417
0.5349 Remote Similarity NPC1813
0.5349 Remote Similarity NPC59051
0.5208 Remote Similarity NPC179764
0.5135 Remote Similarity NPC155263
0.5116 Remote Similarity NPC91495
0.5116 Remote Similarity NPC70387

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC251042 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
0.6579 Remote Similarity NPD3195 Phase 2
0.6579 Remote Similarity NPD3196 Approved
0.6098 Remote Similarity NPD4266 Phase 2
0.5556 Remote Similarity NPD3194 Phase 4
0.5476 Remote Similarity NPD3173 Phase 4
0.5405 Remote Similarity NPD2270 Pre-clinical
0.5405 Remote Similarity NPD633 Phase 3
0.5405 Remote Similarity NPD9448 Phase 2
0.5349 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