Natural Product: NPC208906

Natural Product IDNPC208906
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (R,7E,11E)-14-(Furan-3-Yl)-3,7,11-Trimethyltetradeca-7,11-Dienoic Acid
IUPAC Name (3R,7E,11E)-14-(furan-3-yl)-3,7,11-trimethyltetradeca-7,11-dienoic acid
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL468819
PubChem CID 44577365
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids

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 CMLJLKAJEBCZCF-CVUGZRRRSA-N
Standard InCHI InChI=1S/C21H32O3/c1-17(9-5-11-19(3)15-21(22)23)7-4-8-18(2)10-6-12-20-13-14-24-16-20/h7,10,13-14,16,19H,4-6,8-9,11-12,15H2,1-3H3,(H,22,23)/b17-7+,18-10+/t19-/m1/s1
SMILES C/C(=CCC/C(=C/CCc1ccoc1)/C)/CCC[C@@H](C)CC(=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   332.24 Volume:   376.404
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Van der Waals volume.
Dense:   0.883 LogP:   6.595
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.745
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.469
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The logarithm of aqueous solubility value.
Rotatable Bonds:   12.0 Rigid Bonds:   8.0
TPSA:   50.44
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.466 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.316 Fsp3:   0.571
MCE-18:   16.0
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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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.313 Fluc inhibitor:   0.083
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.004
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.105
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.707 Promiscuous compounds:   0.033

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.984 MDCK Permeability:   -4.828
Pgp-inhibitor:   0.139 Pgp-substrate:   0.003
PAMPA:   0.264
?
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):   0.009
20% Bioavailability (F20%):   0.017 30% Bioavailability (F30%):   0.02
50% Bioavailability (F50%):   0.283

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.972
Plasma Protein Binding (PPB):   96.814% Volume Distribution (VD):   -0.178
Fu: 3.181%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.971 BCRP inhibitor:   0.0
BSEP inhibitor:   0.941

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   0.008
CYP2C19-inhibitor:   0.942 CYP2C19-substrate:   0.564
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.191 CYP2D6-substrate:   0.191
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.656
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.983
HLM stability:   0.543
?
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):  2.881 Half-life (T1/2):  1.116

ADMET: Toxicity

hERG Blockers:  0.15 hERG Blockers (10um):  0.325
Human Hepatotoxicity (H-HT):  0.892 Drug-induced Liver Injury (DILI):  0.298
AMES Toxicity:  0.135 Rat Oral Acute Toxicity:  0.156
Maximum Recommended Daily Dose:  0.673 Skin Sensitization:  0.957
Carcinogencity:  0.146 Eye Corrosion:  0.006
Eye Irritation:  0.934 Respiratory Toxicity:  0.86
Drug-induced Neurotoxicity:  0.282 Ototoxicity:  0.678
Hematotoxicity:  0.436 Drug-induced Nephrotoxicity:  0.823
Genotoxicity:  0.152 RPMI-8226 Immunitoxicity:  0.069
A549 Cytotoxicity:  0.077 Hek293 Cytotoxicity:  0.065
BCF:   1.248
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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:   4.112
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.585
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.302
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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
NPO33064 sarcotragus sp. Species Irciniidae Eukaryota n.a. n.a. n.a. PMID[11678655]
NPO33064 sarcotragus sp. Species Irciniidae Eukaryota n.a. n.a. n.a. PMID[12350153]
NPO33064 sarcotragus sp. Species Irciniidae Eukaryota n.a. n.a. n.a. PMID[18341287]

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
NPT1087 Individual protein Isocitrate lyase Candida albicans IC50 > 200.0 ug.mL-1 DrugMatrix in vivo data: Hematology

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT729 Organism Micrococcus luteus Micrococcus luteus MIC = 12.5 ug.mL-1 PMID[15921433]
NPT566 Organism Salmonella typhimurium Salmonella enterica subsp. enterica serovar Typhimurium MIC = 50.0 ug.mL-1 PMID[25768703]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC > 100.0 ug.mL-1 PMID[20805391]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 100.0 ug.mL-1 PMID[17850214]
NPT19 Organism Escherichia coli Escherichia coli MIC > 100.0 ug.mL-1 PMID[23511018]
NPT766 Organism Proteus vulgaris Proteus vulgaris MIC = 50.0 ug.mL-1 PMID[19245260]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 25.0 ug.mL-1 PMID[22194678]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 100.0 ug.mL-1 PMID[17850214]

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 NPC208906 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
0.7544 Intermediate Similarity NPC144745
0.5571 Remote Similarity NPC474407
0.5538 Remote Similarity NPC105249
0.5493 Remote Similarity NPC283284
0.5493 Remote Similarity NPC289911
0.5079 Remote Similarity NPC26157
0.5079 Remote Similarity NPC1811

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC208906 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