Natural Product: NPC108195

Natural Product IDNPC108195
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Heptadec-9-Ene-4,6-Diyn-1-Ol
IUPAC Name (Z)-heptadec-9-en-4,6-diyn-1-ol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL337824
PubChem CID 44360001
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0003909] Fatty Acyls
        • [CHEMONTID:0001334] Fatty alcohols
          • [CHEMONTID:0002951] Long-chain fatty alcohols

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 TXNKJZICGHLGKD-HJWRWDBZSA-N
Standard InCHI InChI=1S/C17H26O/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18/h8-9,18H,2-7,10,15-17H2,1H3/b9-8-
SMILES CCCCCCC/C=CCC#CC#CCCCO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   246.2 Volume:   298.196
?
Van der Waals volume.
Dense:   0.826 LogP:   5.123
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.49
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.682
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   3.0
TPSA:   20.23
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   1.0 Rings:   0.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.369 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.036 Fsp3:   0.647
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.007 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.002
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.022
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.908 Promiscuous compounds:   0.021

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.973 MDCK Permeability:   -4.711
Pgp-inhibitor:   0.518 Pgp-substrate:   0.0
PAMPA:   0.891
?
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):   0.048
20% Bioavailability (F20%):   0.084 30% Bioavailability (F30%):   0.061
50% Bioavailability (F50%):   0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.031
Plasma Protein Binding (PPB):   99.025% Volume Distribution (VD):   -0.001
Fu: 0.494%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.0
OATP1B3 inhibitor:   0.006 BCRP inhibitor:   0.997
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.99
CYP2C19-inhibitor:   0.016 CYP2C19-substrate:   0.798
CYP2C9-inhibitor:   0.989 CYP2C9-substrate:   0.019
CYP2D6-inhibitor:   0.986 CYP2D6-substrate:   0.827
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.727
CYP2B6-substrate:   0.014 CYP2C8-inhibitor:   1.0
HLM stability:   0.005
?
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):  6.124 Half-life (T1/2):  0.885

ADMET: Toxicity

hERG Blockers:  0.269 hERG Blockers (10um):  0.681
Human Hepatotoxicity (H-HT):  0.412 Drug-induced Liver Injury (DILI):  0.102
AMES Toxicity:  0.239 Rat Oral Acute Toxicity:  0.205
Maximum Recommended Daily Dose:  0.438 Skin Sensitization:  0.997
Carcinogencity:  0.204 Eye Corrosion:  0.998
Eye Irritation:  0.997 Respiratory Toxicity:  0.981
Drug-induced Neurotoxicity:  0.054 Ototoxicity:  0.321
Hematotoxicity:  0.026 Drug-induced Nephrotoxicity:  0.207
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.054
A549 Cytotoxicity:  0.289 Hek293 Cytotoxicity:  0.419
BCF:   2.062
?
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:   4.836
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.005
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.377
?
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
NPO18101 Cicuta virosa Species Apiaceae Eukaryota subterranean part n.a. n.a. PMID[11087575]
NPO18101 Cicuta virosa Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18101 Cicuta virosa Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18101 Cicuta virosa Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18101 Cicuta virosa Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18101 Cicuta virosa Species Apiaceae 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
NPT805 Protein complex GABA-A receptor; anion channel Rattus norvegicus IC50 > 10000.0 nM PMID[8289060]

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
- Mus musculus LD50 > 24.6 mg kg-1 i.p. PMID[18591276]

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 NPC108195 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
0.641 Remote Similarity NPC276825
0.641 Remote Similarity NPC151782
0.6316 Remote Similarity NPC269074
0.6053 Remote Similarity NPC55063
0.6053 Remote Similarity NPC19834
0.6053 Remote Similarity NPC304151
0.6053 Remote Similarity NPC166942
0.575 Remote Similarity NPC48821
0.575 Remote Similarity NPC13418
0.575 Remote Similarity NPC129263
0.5625 Remote Similarity NPC76976
0.5312 Remote Similarity NPC252978
0.525 Remote Similarity NPC481858
0.5238 Remote Similarity NPC256209
0.5116 Remote Similarity NPC180575

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC108195 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
NPD

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