Natural Product: NPC571854

Natural Product IDNPC571854
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Isoleukotoxin diol
IUPAC Name (~{Z},12~{S},13~{S})-12,13-dihydroxyoctadec-9-enoic 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 CQSLTKIXAJTQGA-BTDPBSJTSA-N
Standard InCHI InChI=1S/C18H34O4/c1-2-3-10-13-16(19)17(20)14-11-8-6-4-5-7-9-12-15-18(21)22/h8,11,16-17,19-20H,2-7,9-10,12-15H2,1H3,(H,21,22)/b11-8-/t16-,17-/m0/s1
SMILES CCCCC[C@H](O)[C@@H](O)C/C=CCCCCCCCC(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   314.25 Volume:   349.772
?
Van der Waals volume.
Dense:   0.898 LogP:   4.467
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.185
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.662
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The logarithm of aqueous solubility value.
Rotatable Bonds:   15.0 Rigid Bonds:   2.0
TPSA:   77.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   0.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.315 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.121 Fsp3:   0.833
MCE-18:   3.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.041 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.006
?
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:   0.957 Promiscuous compounds:   0.775

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.144 MDCK Permeability:   -4.794
Pgp-inhibitor:   0.0 Pgp-substrate:   0.005
PAMPA:   0.827
?
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):   0.177
20% Bioavailability (F20%):   0.414 30% Bioavailability (F30%):   0.609
50% Bioavailability (F50%):   0.929

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.034 MRP1:   0.913
Plasma Protein Binding (PPB):   92.798% Volume Distribution (VD):   -0.027
Fu: 5.821%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.066
OATP1B3 inhibitor:   0.928 BCRP inhibitor:   0.103
BSEP inhibitor:   0.406

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.07
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.02 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.983
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):  4.347 Half-life (T1/2):  0.948

ADMET: Toxicity

hERG Blockers:  0.065 hERG Blockers (10um):  0.184
Human Hepatotoxicity (H-HT):  0.371 Drug-induced Liver Injury (DILI):  0.006
AMES Toxicity:  0.075 Rat Oral Acute Toxicity:  0.036
Maximum Recommended Daily Dose:  0.115 Skin Sensitization:  0.993
Carcinogencity:  0.062 Eye Corrosion:  0.822
Eye Irritation:  0.979 Respiratory Toxicity:  0.482
Drug-induced Neurotoxicity:  0.009 Ototoxicity:  0.666
Hematotoxicity:  0.047 Drug-induced Nephrotoxicity:  0.55
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.039
A549 Cytotoxicity:  0.12 Hek293 Cytotoxicity:  0.037
BCF:   0.894
?
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:   3.717
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.043
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.167
?
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
NPO44913 Ipomoea nil Species Convolvulaceae 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 NPC571854 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
0.7857 Intermediate Similarity NPC243532
0.7674 Intermediate Similarity NPC321838
0.6905 Remote Similarity NPC606120
0.6842 Remote Similarity NPC424
0.6842 Remote Similarity NPC36061
0.6842 Remote Similarity NPC69510
0.6842 Remote Similarity NPC77272
0.6842 Remote Similarity NPC290563
0.6842 Remote Similarity NPC139029
0.6842 Remote Similarity NPC281972
0.6842 Remote Similarity NPC261831
0.6842 Remote Similarity NPC87564
0.6667 Remote Similarity NPC255863
0.6667 Remote Similarity NPC136164
0.6667 Remote Similarity NPC245947
0.6596 Remote Similarity NPC49863
0.6579 Remote Similarity NPC281245
0.641 Remote Similarity NPC92114
0.6341 Remote Similarity NPC154245
0.6341 Remote Similarity NPC85813
0.6341 Remote Similarity NPC223697
0.6341 Remote Similarity NPC6095
0.6304 Remote Similarity NPC99619
0.625 Remote Similarity NPC95145
0.625 Remote Similarity NPC26500
0.625 Remote Similarity NPC325642
0.625 Remote Similarity NPC65174
0.6098 Remote Similarity NPC321062
0.6098 Remote Similarity NPC324004
0.6098 Remote Similarity NPC328497
0.5918 Remote Similarity NPC323045
0.5918 Remote Similarity NPC317881
0.5833 Remote Similarity NPC323477
0.5778 Remote Similarity NPC323436
0.5714 Remote Similarity NPC5413
0.5686 Remote Similarity NPC605544
0.5686 Remote Similarity NPC607260
0.5581 Remote Similarity NPC52955
0.5581 Remote Similarity NPC88966
0.5581 Remote Similarity NPC25417
0.5581 Remote Similarity NPC1813
0.5581 Remote Similarity NPC59051
0.5532 Remote Similarity NPC477201
0.54 Remote Similarity NPC470320
0.54 Remote Similarity NPC327112
0.5385 Remote Similarity NPC328653
0.5349 Remote Similarity NPC91495
0.5349 Remote Similarity NPC70387
0.5306 Remote Similarity NPC251042
0.5306 Remote Similarity NPC174447
0.5306 Remote Similarity NPC122521
0.5263 Remote Similarity NPC171736
0.5263 Remote Similarity NPC301585
0.5263 Remote Similarity NPC261080
0.5263 Remote Similarity NPC132565
0.5263 Remote Similarity NPC209970
0.5263 Remote Similarity NPC216630
0.5263 Remote Similarity NPC201844
0.5263 Remote Similarity NPC301696
0.5263 Remote Similarity NPC196924
0.5263 Remote Similarity NPC307783
0.5263 Remote Similarity NPC154186
0.5263 Remote Similarity NPC149184
0.5263 Remote Similarity NPC279026
0.5263 Remote Similarity NPC113928
0.5263 Remote Similarity NPC14227
0.5208 Remote Similarity NPC106851
0.5208 Remote Similarity NPC282788
0.5208 Remote Similarity NPC274927
0.52 Remote Similarity NPC68343
0.52 Remote Similarity NPC318420
0.52 Remote Similarity NPC325627
0.52 Remote Similarity NPC326268
0.52 Remote Similarity NPC328089
0.5106 Remote Similarity NPC225929
0.5102 Remote Similarity NPC179764

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC571854 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 NPD3195 Phase 2
0.6842 Remote Similarity NPD3196 Approved
0.6596 Remote Similarity NPD4247 Clinical (unspecified phase)
0.6512 Remote Similarity NPD3194 Phase 4
0.6341 Remote Similarity NPD4266 Phase 2
0.5714 Remote Similarity NPD3173 Phase 4
0.5581 Remote Similarity NPD3172 Approved
0.54 Remote Similarity NPD4246 Phase 2
0.5263 Remote Similarity NPD2270 Pre-clinical
0.5263 Remote Similarity NPD633 Phase 3
0.5263 Remote Similarity NPD9448 Phase 2
0.52 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