Natural Product: NPC153538

Natural Product IDNPC153538
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Dendroarboreol A
IUPAC Name (3S,8S,9Z)-heptadeca-9,16-dien-4,6-diyne-3,8-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL459425
PubChem CID 5469787
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 XVWSXBIPJCKJCU-RCQSYPNMSA-N
Standard InCHI InChI=1S/C17H24O2/c1-3-5-6-7-8-9-10-14-17(19)15-12-11-13-16(18)4-2/h3,10,14,16-19H,1,4-9H2,2H3/b14-10-/t16-,17-/m0/s1
SMILES CC[C@@H](C#CC#C[C@H](/C=CCCCCCC=C)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   260.18 Volume:   304.35
?
Van der Waals volume.
Dense:   0.855 LogP:   3.635
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.965
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.355
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   4.0
TPSA:   40.46
?
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
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.22 Fsp3:   0.529
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.017 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.016
?
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:   0.769 Promiscuous compounds:   0.041

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.869 MDCK Permeability:   -4.714
Pgp-inhibitor:   0.425 Pgp-substrate:   0.0
PAMPA:   0.969
?
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):   0.0
20% Bioavailability (F20%):   0.0 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.976

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.0
Plasma Protein Binding (PPB):   96.452% Volume Distribution (VD):   -0.115
Fu: 2.773%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.0
OATP1B3 inhibitor:   0.0 BCRP inhibitor:   1.0
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.978
CYP2C19-inhibitor:   0.009 CYP2C19-substrate:   0.12
CYP2C9-inhibitor:   0.898 CYP2C9-substrate:   0.064
CYP2D6-inhibitor:   0.335 CYP2D6-substrate:   0.994
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.983
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.492
?
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):  5.664 Half-life (T1/2):  1.555

ADMET: Toxicity

hERG Blockers:  0.031 hERG Blockers (10um):  0.75
Human Hepatotoxicity (H-HT):  0.138 Drug-induced Liver Injury (DILI):  0.509
AMES Toxicity:  0.491 Rat Oral Acute Toxicity:  0.696
Maximum Recommended Daily Dose:  0.8 Skin Sensitization:  0.995
Carcinogencity:  0.478 Eye Corrosion:  1.0
Eye Irritation:  0.998 Respiratory Toxicity:  1.0
Drug-induced Neurotoxicity:  0.262 Ototoxicity:  0.282
Hematotoxicity:  0.003 Drug-induced Nephrotoxicity:  0.009
Genotoxicity:  0.007 RPMI-8226 Immunitoxicity:  0.09
A549 Cytotoxicity:  0.045 Hek293 Cytotoxicity:  0.492
BCF:   1.357
?
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:   4.029
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.602
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.915
?
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
NPO22011 Myrmekioderma styx Species n.a. n.a. n.a. n.a. n.a. PMID[1431947]
NPO22011 Myrmekioderma styx Species n.a. n.a. n.a. n.a. n.a. PMID[1453179]
NPO21711 Dendropanax arboreus Species Araliaceae Eukaryota n.a. n.a. n.a. PMID[8792622]
NPO21711 Dendropanax arboreus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19387 Hazardia squarrosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21236 Annona crassiflora Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22011 Myrmekioderma styx Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO22185 Cocculus indicus Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22185 Cocculus indicus Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22185 Cocculus indicus Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19387 Hazardia squarrosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22185 Cocculus indicus Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21236 Annona crassiflora Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3495 Matsucoccus feytaudi Species Margarodidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22011 Myrmekioderma styx Species n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO12139 Cylindrotheca closterium Species Bacillariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21711 Dendropanax arboreus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21369 Paullinia scarlatina Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22300 Soulamea amara Species Simaroubaceae 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
NPT113 Cell line RAW264.7 Mus musculus Activity n.a. n.a. n.a. PMID[33476145]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 40500.0 nM PMID[33476145]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 = 4600.0 nM PMID[8792622]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. TGI = 14000.0 nM PMID[8792622]

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 NPC153538 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
0.8438 Intermediate Similarity NPC72699
0.7812 Intermediate Similarity NPC124183
0.7812 Intermediate Similarity NPC482802
0.7714 Intermediate Similarity NPC168510
0.7647 Intermediate Similarity NPC93639
0.7222 Intermediate Similarity NPC482801
0.7059 Intermediate Similarity NPC91226
0.7059 Intermediate Similarity NPC243546
0.7059 Intermediate Similarity NPC31194
0.7059 Intermediate Similarity NPC248884
0.7027 Intermediate Similarity NPC142092
0.697 Remote Similarity NPC243813
0.6757 Remote Similarity NPC484320
0.6585 Remote Similarity NPC29697
0.6486 Remote Similarity NPC481858
0.641 Remote Similarity NPC35141
0.6047 Remote Similarity NPC212730
0.5778 Remote Similarity NPC265551
0.575 Remote Similarity NPC481856
0.561 Remote Similarity NPC85079
0.561 Remote Similarity NPC151782
0.5581 Remote Similarity NPC66460
0.5581 Remote Similarity NPC325929
0.5581 Remote Similarity NPC271282
0.55 Remote Similarity NPC481857
0.5385 Remote Similarity NPC321763
0.5385 Remote Similarity NPC101616
0.5333 Remote Similarity NPC610915
0.5152 Remote Similarity NPC125122
0.5152 Remote Similarity NPC471276
0.5152 Remote Similarity NPC471280
0.5152 Remote Similarity NPC471281
0.5143 Remote Similarity NPC249670
0.5128 Remote Similarity NPC481854
0.5116 Remote Similarity NPC470966

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC153538 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