Natural Product: NPC524738

Natural Product IDNPC524738
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5(R)-HETE
IUPAC Name (5~{R},6~{E},8~{Z},11~{Z},14~{Z})-5-hydroxyicosa-6,8,11,14-tetraenoic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 KGIJOOYOSFUGPC-CABOLEKPSA-N
Standard InCHI InChI=1S/C20H32O3/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-16-19(21)17-15-18-20(22)23/h6-7,9-10,12-14,16,19,21H,2-5,8,11,15,17-18H2,1H3,(H,22,23)/b7-6-,10-9-,13-12-,16-14+/t19-/m0/s1
SMILES CCCCC/C=CC/C=CC/C=CC=C[C@H](O)CCCC(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   320.24 Volume:   367.665
?
Van der Waals volume.
Dense:   0.871 LogP:   4.963
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.106
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.854
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   14.0 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:   0.263 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.345 Fsp3:   0.55
MCE-18:   2.0
?
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:   0.225 Fluc inhibitor:   0.015
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.005
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.016
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.96 Promiscuous compounds:   0.439

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.128 MDCK Permeability:   -4.906
Pgp-inhibitor:   0.001 Pgp-substrate:   0.001
PAMPA:   0.426
?
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):   0.021
20% Bioavailability (F20%):   0.484 30% Bioavailability (F30%):   0.862
50% Bioavailability (F50%):   0.808

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.993
Plasma Protein Binding (PPB):   97.91% Volume Distribution (VD):   -0.574
Fu: 1.638%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.034
OATP1B3 inhibitor:   0.823 BCRP inhibitor:   0.012
BSEP inhibitor:   0.989

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.002
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.892 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.012 CYP2C8-inhibitor:   1.0
HLM stability:   0.027
?
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):  7.58 Half-life (T1/2):  0.372

ADMET: Toxicity

hERG Blockers:  0.273 hERG Blockers (10um):  0.338
Human Hepatotoxicity (H-HT):  0.048 Drug-induced Liver Injury (DILI):  0.0
AMES Toxicity:  0.458 Rat Oral Acute Toxicity:  0.065
Maximum Recommended Daily Dose:  0.068 Skin Sensitization:  1.0
Carcinogencity:  0.023 Eye Corrosion:  0.986
Eye Irritation:  0.998 Respiratory Toxicity:  0.975
Drug-induced Neurotoxicity:  0.016 Ototoxicity:  0.306
Hematotoxicity:  0.002 Drug-induced Nephrotoxicity:  0.387
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.022
A549 Cytotoxicity:  0.202 Hek293 Cytotoxicity:  0.029
BCF:   1.024
?
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:   3.887
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.185
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.857
?
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
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/BF00714468]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. DOI[10.1021/jf00055a023]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. seed n.a. PMID[11539687]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. PMID[12713418]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. PMID[21080643]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. leaf n.a. PMID[21574561]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. husk n.a. PMID[21574561]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. seed n.a. PMID[23292602]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. PMID[29762032]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. pollen n.a. PMID[8987503]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8339 Lithothamnion corallioides Species Hapalidiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15810 Zea mays Species Poaceae Eukaryota Silk Stigma Style n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Stem n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Cob n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Silk Essent. Oil n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Seed Essent. Oil n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Pollen Or Spore n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Oil n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Husk Essent. Oil n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. Database[FooDB]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8339 Lithothamnion corallioides Species Hapalidiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15810 Zea mays Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

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

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 NPC524738 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 NPC323045
1.0 High Similarity NPC317881
0.8372 Intermediate Similarity NPC327112
0.7826 Intermediate Similarity NPC605544
0.7826 Intermediate Similarity NPC607260
0.7778 Intermediate Similarity NPC49863
0.75 Intermediate Similarity NPC255863
0.75 Intermediate Similarity NPC136164
0.75 Intermediate Similarity NPC245947
0.6596 Remote Similarity NPC323477
0.6585 Remote Similarity NPC321062
0.6429 Remote Similarity NPC154245
0.6429 Remote Similarity NPC85813
0.6429 Remote Similarity NPC223697
0.6429 Remote Similarity NPC6095
0.64 Remote Similarity NPC328653
0.625 Remote Similarity NPC325627
0.619 Remote Similarity NPC91495
0.619 Remote Similarity NPC5413
0.617 Remote Similarity NPC324475
0.6122 Remote Similarity NPC320642
0.6047 Remote Similarity NPC59051
0.5932 Remote Similarity NPC319021
0.5918 Remote Similarity NPC321838
0.587 Remote Similarity NPC322002
0.5814 Remote Similarity NPC70387
0.58 Remote Similarity NPC329550
0.5714 Remote Similarity NPC424
0.5714 Remote Similarity NPC36061
0.5714 Remote Similarity NPC69510
0.5714 Remote Similarity NPC77272
0.5714 Remote Similarity NPC290563
0.5714 Remote Similarity NPC139029
0.5714 Remote Similarity NPC243532
0.5714 Remote Similarity NPC281972
0.5714 Remote Similarity NPC261831
0.5714 Remote Similarity NPC87564
0.5682 Remote Similarity NPC52955
0.5682 Remote Similarity NPC88966
0.5682 Remote Similarity NPC25417
0.5682 Remote Similarity NPC1813
0.566 Remote Similarity NPC329249
0.5581 Remote Similarity NPC95145
0.5581 Remote Similarity NPC325642
0.5581 Remote Similarity NPC65174
0.5577 Remote Similarity NPC322461
0.5532 Remote Similarity NPC606120
0.5476 Remote Similarity NPC281245
0.54 Remote Similarity NPC99619
0.5385 Remote Similarity NPC328311
0.537 Remote Similarity NPC92558
0.5349 Remote Similarity NPC92114
0.5312 Remote Similarity NPC319473
0.5227 Remote Similarity NPC149821
0.5192 Remote Similarity NPC325977
0.5192 Remote Similarity NPC470320
0.5106 Remote Similarity NPC318306
0.5098 Remote Similarity NPC323597
0.5098 Remote Similarity NPC211752
0.5098 Remote Similarity NPC323498
0.5088 Remote Similarity NPC260814
0.5088 Remote Similarity NPC323249
0.5088 Remote Similarity NPC27949
0.5088 Remote Similarity NPC39547

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC524738 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
0.8372 Intermediate Similarity NPD4246 Phase 2
0.7778 Intermediate Similarity NPD4247 Clinical (unspecified phase)
0.6429 Remote Similarity NPD4266 Phase 2
0.619 Remote Similarity NPD3173 Phase 4
0.5714 Remote Similarity NPD3195 Phase 2
0.5714 Remote Similarity NPD3196 Approved
0.5682 Remote Similarity NPD3172 Approved
0.5532 Remote Similarity NPD3194 Phase 4
0.5294 Remote Similarity NPD39 Phase 4
0.5088 Remote Similarity NPD4271 Phase 4

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