Natural Product: NPC177420

Natural Product IDNPC177420
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Gibbilimbol A
IUPAC Name 4-[(E)-dec-4-enyl]phenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL503936
PubChem CID 10263365
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000134] Phenols
        • [CHEMONTID:0004646] 1-hydroxy-2-unsubstituted benzenoids

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 LMJPVRXXPPOFAM-VOTSOKGWSA-N
Standard InCHI InChI=1S/C16H24O/c1-2-3-4-5-6-7-8-9-10-15-11-13-16(17)14-12-15/h6-7,11-14,17H,2-5,8-10H2,1H3/b7-6+
SMILES CCCCC/C=C/CCCc1ccc(cc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   232.18 Volume:   274.98
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Van der Waals volume.
Dense:   0.844 LogP:   5.702
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.009
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.908
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The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   7.0
TPSA:   20.23
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Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.501 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.965 Fsp3:   0.5
MCE-18:   5.0
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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:   0.424 Fluc inhibitor:   0.38
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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:   0.151
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.997 Promiscuous compounds:   0.184

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.835 MDCK Permeability:   -4.714
Pgp-inhibitor:   0.448 Pgp-substrate:   0.076
PAMPA:   0.005
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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):   0.017
20% Bioavailability (F20%):   0.25 30% Bioavailability (F30%):   0.748
50% Bioavailability (F50%):   0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.454
Plasma Protein Binding (PPB):   98.726% Volume Distribution (VD):   -0.341
Fu: 0.636%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.867
OATP1B3 inhibitor:   0.978 BCRP inhibitor:   0.194
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.827
CYP2C19-inhibitor:   0.298 CYP2C19-substrate:   0.961
CYP2C9-inhibitor:   0.349 CYP2C9-substrate:   0.413
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.02 CYP2C8-inhibitor:   1.0
HLM stability:   0.767
?
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):  6.906 Half-life (T1/2):  0.433

ADMET: Toxicity

hERG Blockers:  0.509 hERG Blockers (10um):  0.851
Human Hepatotoxicity (H-HT):  0.78 Drug-induced Liver Injury (DILI):  0.025
AMES Toxicity:  0.092 Rat Oral Acute Toxicity:  0.063
Maximum Recommended Daily Dose:  0.454 Skin Sensitization:  0.992
Carcinogencity:  0.079 Eye Corrosion:  0.636
Eye Irritation:  0.981 Respiratory Toxicity:  0.746
Drug-induced Neurotoxicity:  0.165 Ototoxicity:  0.265
Hematotoxicity:  0.076 Drug-induced Nephrotoxicity:  0.336
Genotoxicity:  0.002 RPMI-8226 Immunitoxicity:  0.063
A549 Cytotoxicity:  0.741 Hek293 Cytotoxicity:  0.78
BCF:   2.374
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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:   5.211
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.744
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.62
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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
NPO27498 Piper gibbilimbum Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[9677279]
NPO27498 Piper gibbilimbum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27498 Piper gibbilimbum Species Piperaceae 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
NPT91 Cell line KB Homo sapiens ED50 = 4.4 ug ml-1 PMID[24996136]
NPT580 Organism Trypanosoma cruzi Trypanosoma cruzi IC50 = 102500.0 nM PMID[10579838]
NPT1021 Organism Leishmania infantum Leishmania infantum IC50 = 135700.0 nM PubChem BioAssay data set
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MIC = 4.0 ug.mL-1 PMID[24864039]
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis IZ < 2.0 mm PMID[18838581]
NPT314 Organism Bacillus cereus Bacillus cereus MIC = 4.0 ug.mL-1 PMID[24996136]
NPT314 Organism Bacillus cereus Bacillus cereus IZ < 2.0 mm PMID[18838581]
NPT2 Others Unspecified n.a. Ratio CC50/IC50 = 2.2 n.a. PMID[17696332]
NPT2 Others Unspecified n.a. Ratio CC50/IC50 = 1.7 n.a. PMID[7069725]

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
- Artemia salina LD50 = 5.3 ug ml-1 PMID[24904965]

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 NPC177420 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
0.9697 High Similarity NPC55561
0.8485 Intermediate Similarity NPC25493
0.7568 Intermediate Similarity NPC280347
0.7368 Intermediate Similarity NPC196479
0.7222 Intermediate Similarity NPC113460
0.6857 Remote Similarity NPC123273
0.6857 Remote Similarity NPC318325
0.6765 Remote Similarity NPC242240
0.6667 Remote Similarity NPC23167
0.6341 Remote Similarity NPC166761
0.619 Remote Similarity NPC94139
0.619 Remote Similarity NPC147284
0.5952 Remote Similarity NPC483454
0.5952 Remote Similarity NPC162314
0.5854 Remote Similarity NPC146798
0.5854 Remote Similarity NPC222522
0.5854 Remote Similarity NPC106396
0.5854 Remote Similarity NPC94351
0.5854 Remote Similarity NPC168303
0.5814 Remote Similarity NPC488416
0.5714 Remote Similarity NPC487734
0.561 Remote Similarity NPC53051
0.561 Remote Similarity NPC24404
0.561 Remote Similarity NPC313030
0.561 Remote Similarity NPC39664
0.5588 Remote Similarity NPC608485
0.5455 Remote Similarity NPC71002
0.5455 Remote Similarity NPC249828
0.5435 Remote Similarity NPC210497
0.5349 Remote Similarity NPC232523
0.5227 Remote Similarity NPC488413
0.5227 Remote Similarity NPC488412
0.5208 Remote Similarity NPC113457
0.5122 Remote Similarity NPC470700
0.5122 Remote Similarity NPC54844
0.5122 Remote Similarity NPC39097
0.5122 Remote Similarity NPC302681
0.5122 Remote Similarity NPC118286
0.5122 Remote Similarity NPC109691
0.5111 Remote Similarity NPC302219
0.5111 Remote Similarity NPC129373

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC177420 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