Natural Product: NPC471280

Natural Product IDNPC471280
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (4E,12E)-Hexadeca-4,12-Dien-1,15-Diyne-3,14-Diol
IUPAC Name (4E,12E)-hexadeca-4,12-dien-1,15-diyne-3,14-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2408395
PubChem CID 71745538
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 YUTFLVQSQJNSGY-PHEQNACWSA-N
Standard InCHI InChI=1S/C16H22O2/c1-3-15(17)13-11-9-7-5-6-8-10-12-14-16(18)4-2/h1-2,11-18H,5-10H2/b13-11+,14-12+
SMILES C#CC(C=CCCCCCCC=CC(C#C)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   246.16 Volume:   287.054
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Van der Waals volume.
Dense:   0.858 LogP:   3.318
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.601
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.286
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The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 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:   0.373 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.076 Fsp3:   0.5
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:   0.005 Fluc inhibitor:   0.0
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.002
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.84 Promiscuous compounds:   0.009

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.64 MDCK Permeability:   -4.715
Pgp-inhibitor:   0.0 Pgp-substrate:   0.0
PAMPA:   0.562
?
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):   0.002
20% Bioavailability (F20%):   0.0 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.147

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.386 MRP1:   0.0
Plasma Protein Binding (PPB):   96.646% Volume Distribution (VD):   -0.034
Fu: 1.797%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.042
OATP1B3 inhibitor:   0.964 BCRP inhibitor:   0.813
BSEP inhibitor:   0.925

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   0.929
CYP2C19-inhibitor:   0.877 CYP2C19-substrate:   0.016
CYP2C9-inhibitor:   0.997 CYP2C9-substrate:   0.762
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.983
CYP3A4-inhibitor:   0.67 CYP3A4-substrate:   0.308
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.994
HLM stability:   0.971
?
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):  4.988 Half-life (T1/2):  1.21

ADMET: Toxicity

hERG Blockers:  0.006 hERG Blockers (10um):  0.509
Human Hepatotoxicity (H-HT):  0.63 Drug-induced Liver Injury (DILI):  0.002
AMES Toxicity:  0.474 Rat Oral Acute Toxicity:  0.829
Maximum Recommended Daily Dose:  0.736 Skin Sensitization:  0.434
Carcinogencity:  0.074 Eye Corrosion:  0.44
Eye Irritation:  0.95 Respiratory Toxicity:  1.0
Drug-induced Neurotoxicity:  0.112 Ototoxicity:  0.951
Hematotoxicity:  0.001 Drug-induced Nephrotoxicity:  0.929
Genotoxicity:  0.006 RPMI-8226 Immunitoxicity:  0.219
A549 Cytotoxicity:  0.0 Hek293 Cytotoxicity:  0.018
BCF:   1.644
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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:   5.093
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.725
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.028
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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
NPO33070 Callyspongia sp. Species n.a. n.a. n.a. red sea n.a. PMID[12762806]
NPO33070 Callyspongia sp. Species n.a. n.a. n.a. n.a. n.a. PMID[18027906]
NPO33070 Callyspongia sp. Species n.a. n.a. n.a. n.a. n.a. PMID[22469701]
NPO33070 Callyspongia sp. Species n.a. n.a. n.a. collected by hand at a depth of 10 m off the shore of Iriomote Island, Okinawa Prefecture, Japan 2009-JUN PMID[23855338]
NPO33070 Callyspongia sp. Species n.a. n.a. n.a. n.a. n.a. PMID[24948562]
NPO33070 Callyspongia sp. Species n.a. n.a. n.a. n.a. n.a. PMID[27015002]
NPO33070 Callyspongia sp. Species n.a. n.a. n.a. New Guinea n.a. PMID[8158156]
NPO33070 Callyspongia sp. Species n.a. n.a. 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 9400.0 nM PMID[23855338]

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 NPC471280 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
1.0 High Similarity NPC125122
1.0 High Similarity NPC471276
1.0 High Similarity NPC471281
0.9524 High Similarity NPC170776
0.9524 High Similarity NPC9273
0.9524 High Similarity NPC165447
0.9524 High Similarity NPC471959
0.9524 High Similarity NPC199286
0.9524 High Similarity NPC489046
0.9524 High Similarity NPC76198
0.9524 High Similarity NPC610719
0.9091 High Similarity NPC607242
0.8696 High Similarity NPC249670
0.8333 Intermediate Similarity NPC474642
0.8333 Intermediate Similarity NPC473913
0.7692 Intermediate Similarity NPC474644
0.6897 Remote Similarity NPC471239
0.6897 Remote Similarity NPC161838
0.6897 Remote Similarity NPC474643
0.6897 Remote Similarity NPC473865
0.6897 Remote Similarity NPC55383
0.6667 Remote Similarity NPC471960
0.6667 Remote Similarity NPC477727
0.6061 Remote Similarity NPC197272
0.5882 Remote Similarity NPC89824
0.5882 Remote Similarity NPC475477
0.5882 Remote Similarity NPC256656
0.5882 Remote Similarity NPC294278
0.5882 Remote Similarity NPC477723
0.5714 Remote Similarity NPC471278
0.5714 Remote Similarity NPC470966
0.5667 Remote Similarity NPC124183
0.5667 Remote Similarity NPC482802
0.5556 Remote Similarity NPC48058
0.5556 Remote Similarity NPC470963
0.5556 Remote Similarity NPC477661
0.5556 Remote Similarity NPC603233
0.5556 Remote Similarity NPC607245
0.5484 Remote Similarity NPC91226
0.5484 Remote Similarity NPC243546
0.5484 Remote Similarity NPC31194
0.5484 Remote Similarity NPC248884
0.5405 Remote Similarity NPC470970
0.5312 Remote Similarity NPC72699
0.5263 Remote Similarity NPC224148
0.5263 Remote Similarity NPC477726
0.5263 Remote Similarity NPC477725
0.5152 Remote Similarity NPC153538
0.5152 Remote Similarity NPC93639
0.5128 Remote Similarity NPC473896
0.5128 Remote Similarity NPC473735
0.5128 Remote Similarity NPC470969
0.5128 Remote Similarity NPC146551
0.5128 Remote Similarity NPC329608

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC471280 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