Natural Product: NPC534230

Natural Product IDNPC534230
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DTXSID101177926
IUPAC Name (5~{Z},8~{Z},11~{Z},13~{R},14~{Z})-13-hydroxyicosa-5,8,11,14-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 SAKQICHVWOJSNI-PRVIWIHFSA-N
Standard InCHI InChI=1S/C20H32O3/c1-2-3-4-10-13-16-19(21)17-14-11-8-6-5-7-9-12-15-18-20(22)23/h6-9,13-14,16-17,19,21H,2-5,10-12,15,18H2,1H3,(H,22,23)/b8-6-,9-7-,16-13-,17-14-/t19-/m1/s1
SMILES CCCCC/C=C[C@@H](O)/C=CC/C=CC/C=CCCCC(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   320.24 Volume:   367.665
?
Van der Waals volume.
Dense:   0.871 LogP:   5.323
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.278
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.765
?
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:   0.342 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.486 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:   0.127 Fluc inhibitor:   0.004
?
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:   0.965 Promiscuous compounds:   0.54

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.008 MDCK Permeability:   -4.781
Pgp-inhibitor:   0.003 Pgp-substrate:   0.001
PAMPA:   0.208
?
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%):   0.068 30% Bioavailability (F30%):   0.598
50% Bioavailability (F50%):   0.419

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.992
Plasma Protein Binding (PPB):   97.072% Volume Distribution (VD):   -0.717
Fu: 2.299%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.01
OATP1B3 inhibitor:   0.246 BCRP inhibitor:   0.025
BSEP inhibitor:   0.981

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.034 CYP2C19-substrate:   0.034
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.012 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.053
CYP2B6-substrate:   0.995 CYP2C8-inhibitor:   0.976
HLM stability:   0.029
?
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):  6.385 Half-life (T1/2):  0.306

ADMET: Toxicity

hERG Blockers:  0.118 hERG Blockers (10um):  0.14
Human Hepatotoxicity (H-HT):  0.006 Drug-induced Liver Injury (DILI):  0.0
AMES Toxicity:  0.478 Rat Oral Acute Toxicity:  0.004
Maximum Recommended Daily Dose:  0.001 Skin Sensitization:  1.0
Carcinogencity:  0.0 Eye Corrosion:  1.0
Eye Irritation:  1.0 Respiratory Toxicity:  0.95
Drug-induced Neurotoxicity:  0.001 Ototoxicity:  0.129
Hematotoxicity:  0.0 Drug-induced Nephrotoxicity:  0.218
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.019
A549 Cytotoxicity:  0.037 Hek293 Cytotoxicity:  0.002
BCF:   0.96
?
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:   3.818
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.105
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.585
?
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
NPO8339 Lithothamnion corallioides Species Hapalidiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8339 Lithothamnion corallioides Species Hapalidiaceae 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 NPC534230 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
0.7778 Intermediate Similarity NPC91495
0.7568 Intermediate Similarity NPC59051
0.6957 Remote Similarity NPC605544
0.6957 Remote Similarity NPC607260
0.6842 Remote Similarity NPC321062
0.6842 Remote Similarity NPC5413
0.6667 Remote Similarity NPC327112
0.6667 Remote Similarity NPC154245
0.6667 Remote Similarity NPC85813
0.6667 Remote Similarity NPC223697
0.6667 Remote Similarity NPC6095
0.6522 Remote Similarity NPC323045
0.6522 Remote Similarity NPC317881
0.6444 Remote Similarity NPC321838
0.6222 Remote Similarity NPC323597
0.6222 Remote Similarity NPC211752
0.6222 Remote Similarity NPC323498
0.6053 Remote Similarity NPC117572
0.6047 Remote Similarity NPC323436
0.6 Remote Similarity NPC70387
0.5897 Remote Similarity NPC424
0.5897 Remote Similarity NPC36061
0.5897 Remote Similarity NPC69510
0.5897 Remote Similarity NPC77272
0.5897 Remote Similarity NPC290563
0.5897 Remote Similarity NPC139029
0.5897 Remote Similarity NPC281972
0.5897 Remote Similarity NPC92114
0.5897 Remote Similarity NPC261831
0.5897 Remote Similarity NPC87564
0.5854 Remote Similarity NPC52955
0.5854 Remote Similarity NPC88966
0.5854 Remote Similarity NPC25417
0.5854 Remote Similarity NPC1813
0.58 Remote Similarity NPC329249
0.575 Remote Similarity NPC149821
0.5714 Remote Similarity NPC322461
0.5641 Remote Similarity NPC281245
0.5625 Remote Similarity NPC320642
0.5532 Remote Similarity NPC243532
0.5532 Remote Similarity NPC255863
0.5532 Remote Similarity NPC136164
0.5532 Remote Similarity NPC245947
0.551 Remote Similarity NPC328311
0.551 Remote Similarity NPC49863
0.5417 Remote Similarity NPC320305
0.5417 Remote Similarity NPC317583
0.5366 Remote Similarity NPC95145
0.5366 Remote Similarity NPC325642
0.5366 Remote Similarity NPC207292
0.5366 Remote Similarity NPC65174
0.5333 Remote Similarity NPC606120
0.5306 Remote Similarity NPC325977
0.5306 Remote Similarity NPC329550
0.5238 Remote Similarity NPC48162

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC534230 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
0.6842 Remote Similarity NPD3173 Phase 4
0.6667 Remote Similarity NPD4246 Phase 2
0.6667 Remote Similarity NPD4266 Phase 2
0.6087 Remote Similarity NPD39 Phase 4
0.6053 Remote Similarity NPD4222 Phase 3
0.5897 Remote Similarity NPD3195 Phase 2
0.5897 Remote Similarity NPD3196 Approved
0.5854 Remote Similarity NPD3172 Approved
0.5682 Remote Similarity NPD3194 Phase 4
0.551 Remote Similarity NPD4247 Clinical (unspecified phase)

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