Natural Product: NPC85079

Natural Product IDNPC85079
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 8S-Heptadeca-2(Z),9(Z)-Diene-4,6-Diyne-1,8-Diol
IUPAC Name (2Z,8S,9Z)-heptadeca-2,9-dien-4,6-diyne-1,8-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL463984
PubChem CID 10400397
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 UECWLXACMXYTFN-HVIKZBMUSA-N
Standard InCHI InChI=1S/C17H24O2/c1-2-3-4-5-6-8-11-14-17(19)15-12-9-7-10-13-16-18/h10-11,13-14,17-19H,2-6,8,16H2,1H3/b13-10-,14-11-/t17-/m0/s1
SMILES CCCCCCC/C=C[C@@H](C#CC#C/C=CCO)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   260.18 Volume:   304.35
?
Van der Waals volume.
Dense:   0.855 LogP:   3.658
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.05
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.43
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   4.0
TPSA:   40.46
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Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   0.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.4 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.841 Fsp3:   0.529
MCE-18:   1.0
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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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.083 Fluc inhibitor:   0.001
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.034
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.003
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.723 Promiscuous compounds:   0.12

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.816 MDCK Permeability:   -4.707
Pgp-inhibitor:   0.033 Pgp-substrate:   0.0
PAMPA:   0.649
?
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):   0.003
20% Bioavailability (F20%):   0.004 30% Bioavailability (F30%):   0.02
50% Bioavailability (F50%):   0.954

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.001
Plasma Protein Binding (PPB):   98.915% Volume Distribution (VD):   -0.121
Fu: 1.119%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.0
OATP1B3 inhibitor:   0.014 BCRP inhibitor:   0.992
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.903
CYP2C19-inhibitor:   0.018 CYP2C19-substrate:   0.141
CYP2C9-inhibitor:   0.993 CYP2C9-substrate:   0.475
CYP2D6-inhibitor:   0.848 CYP2D6-substrate:   0.963
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.365
?
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):  5.004 Half-life (T1/2):  1.137

ADMET: Toxicity

hERG Blockers:  0.1 hERG Blockers (10um):  0.649
Human Hepatotoxicity (H-HT):  0.294 Drug-induced Liver Injury (DILI):  0.549
AMES Toxicity:  0.315 Rat Oral Acute Toxicity:  0.411
Maximum Recommended Daily Dose:  0.506 Skin Sensitization:  0.989
Carcinogencity:  0.305 Eye Corrosion:  0.999
Eye Irritation:  0.998 Respiratory Toxicity:  1.0
Drug-induced Neurotoxicity:  0.078 Ototoxicity:  0.285
Hematotoxicity:  0.013 Drug-induced Nephrotoxicity:  0.039
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.074
A549 Cytotoxicity:  0.228 Hek293 Cytotoxicity:  0.492
BCF:   1.708
?
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:   4.631
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.02
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.25
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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
NPO11237 Bupleurum salicifolium Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[24242108]
NPO11237 Bupleurum salicifolium Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[7964800]
NPO11237 Bupleurum salicifolium 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 10.5 ug.mL-1 DOI[10.6019/CHEMBL1201861]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 10.0 ug.mL-1 DOI[10.6019/CHEMBL1201861]

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 NPC85079 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
0.8378 Intermediate Similarity NPC35141
0.6923 Remote Similarity NPC482801
0.6757 Remote Similarity NPC91226
0.6757 Remote Similarity NPC243546
0.6757 Remote Similarity NPC31194
0.6757 Remote Similarity NPC248884
0.6579 Remote Similarity NPC72699
0.65 Remote Similarity NPC484320
0.619 Remote Similarity NPC151782
0.6098 Remote Similarity NPC269074
0.6053 Remote Similarity NPC206906
0.5854 Remote Similarity NPC304151
0.5714 Remote Similarity NPC168510
0.5641 Remote Similarity NPC124183
0.5641 Remote Similarity NPC482802
0.5625 Remote Similarity NPC265551
0.561 Remote Similarity NPC153538
0.561 Remote Similarity NPC93639
0.5532 Remote Similarity NPC193975
0.5405 Remote Similarity NPC249670
0.5349 Remote Similarity NPC49059
0.5349 Remote Similarity NPC481849
0.5349 Remote Similarity NPC201681
0.5333 Remote Similarity NPC180575
0.5263 Remote Similarity NPC474642
0.5263 Remote Similarity NPC473913
0.5227 Remote Similarity NPC142092

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC85079 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