Natural Product: NPC130595

Natural Product IDNPC130595
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Octanoic Acid 4-Hydroxy-3-Methoxy-Benzylamide
IUPAC Name N-[(4-hydroxy-3-methoxyphenyl)methyl]octanamide
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL86443
PubChem CID 5316427
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000134] Phenols
        • [CHEMONTID:0000190] Methoxyphenols

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 JYZDUDMWJFJCON-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H25NO3/c1-3-4-5-6-7-8-16(19)17-12-13-9-10-14(18)15(11-13)20-2/h9-11,18H,3-8,12H2,1-2H3,(H,17,19)
SMILES CCCCCCCC(=NCc1ccc(c(c1)OC)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   279.18 Volume:   303.557
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Van der Waals volume.
Dense:   0.92 LogP:   3.517
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.81
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.142
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The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   7.0
TPSA:   62.05
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.404 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.327 Fsp3:   0.562
MCE-18:   7.0
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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:   1 PAINS Alert:   0
Colloidal aggregators:   0.271 Fluc inhibitor:   0.032
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.022
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.402
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.026 Promiscuous compounds:   0.125

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.941 MDCK Permeability:   -4.704
Pgp-inhibitor:   0.108 Pgp-substrate:   0.026
PAMPA:   0.036
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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):   0.116
20% Bioavailability (F20%):   0.527 30% Bioavailability (F30%):   0.476
50% Bioavailability (F50%):   0.399

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.064 MRP1:   0.927
Plasma Protein Binding (PPB):   95.523% Volume Distribution (VD):   -0.047
Fu: 4.863%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.933
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.016
BSEP inhibitor:   0.855

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.961
CYP2C19-inhibitor:   0.571 CYP2C19-substrate:   0.555
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.739
CYP2D6-inhibitor:   0.983 CYP2D6-substrate:   0.039
CYP3A4-inhibitor:   0.003 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.059 CYP2C8-inhibitor:   1.0
HLM stability:   0.084
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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):  5.446 Half-life (T1/2):  0.709

ADMET: Toxicity

hERG Blockers:  0.109 hERG Blockers (10um):  0.519
Human Hepatotoxicity (H-HT):  0.889 Drug-induced Liver Injury (DILI):  0.718
AMES Toxicity:  0.648 Rat Oral Acute Toxicity:  0.194
Maximum Recommended Daily Dose:  0.477 Skin Sensitization:  0.997
Carcinogencity:  0.865 Eye Corrosion:  0.008
Eye Irritation:  0.948 Respiratory Toxicity:  0.883
Drug-induced Neurotoxicity:  0.373 Ototoxicity:  0.352
Hematotoxicity:  0.349 Drug-induced Nephrotoxicity:  0.747
Genotoxicity:  0.019 RPMI-8226 Immunitoxicity:  0.014
A549 Cytotoxicity:  0.017 Hek293 Cytotoxicity:  0.102
BCF:   1.551
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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:   4.265
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.179
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.766
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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
NPO24552 Capsicum frutescens Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9481 Strophanthus divaricatus Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24552 Capsicum frutescens Species Solanaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9481 Strophanthus divaricatus Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24552 Capsicum frutescens Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9481 Strophanthus divaricatus Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24552 Capsicum frutescens Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9481 Strophanthus divaricatus Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]

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

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Latency > 51.3 n.a. PMID[8410971]
NPT32 Organism Mus musculus Mus musculus Response = 6.0 n.a. PMID[8410971]
NPT32 Organism Mus musculus Mus musculus Inhibition = 45.8 % PMID[8410971]
NPT32 Organism Mus musculus Mus musculus Lethality = 90.0 % PMID[8410971]





 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 NPC130595 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 NPC285078
1.0 High Similarity NPC93882
1.0 High Similarity NPC255540
0.88 High Similarity NPC6854
0.8571 High Similarity NPC218530
0.7593 Intermediate Similarity NPC308885
0.7593 Intermediate Similarity NPC255550
0.6471 Remote Similarity NPC74427
0.6346 Remote Similarity NPC471308
0.6346 Remote Similarity NPC483618
0.6346 Remote Similarity NPC17388
0.569 Remote Similarity NPC53596
0.551 Remote Similarity NPC471307
0.551 Remote Similarity NPC78041
0.551 Remote Similarity NPC141139
0.55 Remote Similarity NPC483621
0.541 Remote Similarity NPC289330
0.5231 Remote Similarity NPC275027
0.5172 Remote Similarity NPC605032

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC130595 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
1.0 High Similarity NPD2674 Phase 3
0.7593 Intermediate Similarity NPD3144 Phase 3
0.7593 Intermediate Similarity NPD3145 Phase 4
0.5231 Remote Similarity NPD7153 Discontinued

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