Natural Product: NPC504322

Natural Product IDNPC504322
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 10R-HODE
IUPAC Name (8~{E},10~{R},12~{Z})-10-hydroxyoctadeca-8,12-dienoic 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 XUDNDTZOWNNWHA-HLGVZOAESA-N
Standard InCHI InChI=1S/C18H32O3/c1-2-3-4-5-8-11-14-17(19)15-12-9-6-7-10-13-16-18(20)21/h8,11-12,15,17,19H,2-7,9-10,13-14,16H2,1H3,(H,20,21)/b11-8-,15-12+/t17-/m1/s1
SMILES CCCCC/C=CC[C@@H](O)/C=C/CCCCCCC(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   296.24 Volume:   338.345
?
Van der Waals volume.
Dense:   0.876 LogP:   4.527
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.13
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.721
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   14.0 Rigid Bonds:   3.0
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:   0.355 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.947 Fsp3:   0.722
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:   0.078 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.003
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.986 Promiscuous compounds:   0.859

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.152 MDCK Permeability:   -4.811
Pgp-inhibitor:   0.001 Pgp-substrate:   0.001
PAMPA:   0.316
?
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):   0.012
20% Bioavailability (F20%):   0.059 30% Bioavailability (F30%):   0.68
50% Bioavailability (F50%):   0.581

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.875
Plasma Protein Binding (PPB):   94.611% Volume Distribution (VD):   -0.175
Fu: 5.377%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.193
OATP1B3 inhibitor:   0.947 BCRP inhibitor:   0.005
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.191
CYP2C9-inhibitor:   0.86 CYP2C9-substrate:   0.024
CYP2D6-inhibitor:   0.558 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.231
?
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):  3.878 Half-life (T1/2):  0.863

ADMET: Toxicity

hERG Blockers:  0.063 hERG Blockers (10um):  0.206
Human Hepatotoxicity (H-HT):  0.69 Drug-induced Liver Injury (DILI):  0.044
AMES Toxicity:  0.033 Rat Oral Acute Toxicity:  0.032
Maximum Recommended Daily Dose:  0.455 Skin Sensitization:  0.997
Carcinogencity:  0.04 Eye Corrosion:  0.839
Eye Irritation:  0.991 Respiratory Toxicity:  0.887
Drug-induced Neurotoxicity:  0.033 Ototoxicity:  0.562
Hematotoxicity:  0.059 Drug-induced Nephrotoxicity:  0.678
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.086
A549 Cytotoxicity:  0.163 Hek293 Cytotoxicity:  0.085
BCF:   0.982
?
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:   3.925
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.23
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.31
?
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
NPO45640 Pholiota lubrica Species Strophariaceae 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

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 NPC504322 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
0.75 Intermediate Similarity NPC49863
0.7209 Intermediate Similarity NPC243532
0.7174 Intermediate Similarity NPC605544
0.7174 Intermediate Similarity NPC607260
0.7027 Intermediate Similarity NPC424
0.7027 Intermediate Similarity NPC36061
0.7027 Intermediate Similarity NPC69510
0.7027 Intermediate Similarity NPC77272
0.7027 Intermediate Similarity NPC290563
0.7027 Intermediate Similarity NPC139029
0.7027 Intermediate Similarity NPC281972
0.7027 Intermediate Similarity NPC261831
0.7027 Intermediate Similarity NPC87564
0.6818 Remote Similarity NPC255863
0.6818 Remote Similarity NPC136164
0.6818 Remote Similarity NPC245947
0.6757 Remote Similarity NPC281245
0.6667 Remote Similarity NPC323477
0.6579 Remote Similarity NPC92114
0.65 Remote Similarity NPC154245
0.65 Remote Similarity NPC85813
0.65 Remote Similarity NPC223697
0.65 Remote Similarity NPC6095
0.641 Remote Similarity NPC95145
0.641 Remote Similarity NPC325642
0.641 Remote Similarity NPC65174
0.6279 Remote Similarity NPC606120
0.625 Remote Similarity NPC321062
0.6122 Remote Similarity NPC328653
0.6042 Remote Similarity NPC323045
0.6042 Remote Similarity NPC317881
0.5854 Remote Similarity NPC5413
0.5745 Remote Similarity NPC99619
0.5714 Remote Similarity NPC52955
0.5714 Remote Similarity NPC88966
0.5714 Remote Similarity NPC25417
0.5714 Remote Similarity NPC26500
0.5714 Remote Similarity NPC1813
0.5714 Remote Similarity NPC59051
0.5652 Remote Similarity NPC477201
0.551 Remote Similarity NPC470320
0.551 Remote Similarity NPC327112
0.5476 Remote Similarity NPC91495
0.5476 Remote Similarity NPC324004
0.5476 Remote Similarity NPC328497
0.5476 Remote Similarity NPC70387
0.5417 Remote Similarity NPC251042
0.5417 Remote Similarity NPC174447
0.5417 Remote Similarity NPC122521
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
0.5319 Remote Similarity NPC106851
0.5319 Remote Similarity NPC282788
0.5319 Remote Similarity NPC274927
0.5306 Remote Similarity NPC68343
0.5306 Remote Similarity NPC321838
0.5306 Remote Similarity NPC318420
0.5306 Remote Similarity NPC326268
0.5306 Remote Similarity NPC328089
0.5208 Remote Similarity NPC324475
0.5208 Remote Similarity NPC179764
0.5135 Remote Similarity NPC155263
0.5102 Remote Similarity NPC473863

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC504322 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
0.75 Intermediate Similarity NPD4247 Clinical (unspecified phase)
0.7027 Intermediate Similarity NPD3195 Phase 2
0.7027 Intermediate Similarity NPD3196 Approved
0.6667 Remote Similarity NPD3194 Phase 4
0.65 Remote Similarity NPD4266 Phase 2
0.5854 Remote Similarity NPD3173 Phase 4
0.5714 Remote Similarity NPD3172 Approved
0.551 Remote Similarity NPD4246 Phase 2
0.5405 Remote Similarity NPD2270 Pre-clinical
0.5405 Remote Similarity NPD633 Phase 3
0.5405 Remote Similarity NPD9448 Phase 2
0.5306 Remote Similarity NPD39 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