Natural Product: NPC4164

Natural Product IDNPC4164
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2-Hydroxybenzyl 2'-Methoxybenzoate
IUPAC Name (2-methoxyphenyl)methyl 2-hydroxybenzoate
Synonyms 2-Hydroxybenzyl 2'-Methoxybenzoate
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL495645
PubChem CID 7798110
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000176] Benzoic acids and derivatives
          • [CHEMONTID:0001350] Benzoic acid esters
            • [CHEMONTID:0004700] o-Hydroxybenzoic acid esters

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 YLHAQKVIXLQIFW-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H14O4/c1-18-14-9-5-2-6-11(14)10-19-15(17)12-7-3-4-8-13(12)16/h2-9,16H,10H2,1H3
SMILES COc1ccccc1COC(=O)c1ccccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   258.09 Volume:   267.589
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Van der Waals volume.
Dense:   0.965 LogP:   3.332
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.217
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.651
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   13.0
TPSA:   55.76
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.857 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.639 Fsp3:   0.133
MCE-18:   11.0
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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:   0 PAINS Alert:   0
Colloidal aggregators:   0.113 Fluc inhibitor:   0.394
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.103
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.346
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.937 Promiscuous compounds:   0.658

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.13 MDCK Permeability:   -4.58
Pgp-inhibitor:   0.802 Pgp-substrate:   0.001
PAMPA:   0.053
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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):   0.131
20% Bioavailability (F20%):   0.415 30% Bioavailability (F30%):   0.882
50% Bioavailability (F50%):   0.451

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.267 MRP1:   0.461
Plasma Protein Binding (PPB):   98.406% Volume Distribution (VD):   -0.792
Fu: 1.599%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.979
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.012
BSEP inhibitor:   0.986

ADMET: Metabolism

CYP1A2-inhibitor:   0.09 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.036 CYP2C19-substrate:   0.89
CYP2C9-inhibitor:   0.563 CYP2C9-substrate:   0.008
CYP2D6-inhibitor:   0.431 CYP2D6-substrate:   0.236
CYP3A4-inhibitor:   0.165 CYP3A4-substrate:   0.501
CYP2B6-substrate:   0.006 CYP2C8-inhibitor:   0.999
HLM stability:   0.82
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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):  5.0 Half-life (T1/2):  0.652

ADMET: Toxicity

hERG Blockers:  0.138 hERG Blockers (10um):  0.713
Human Hepatotoxicity (H-HT):  0.04 Drug-induced Liver Injury (DILI):  0.327
AMES Toxicity:  0.174 Rat Oral Acute Toxicity:  0.039
Maximum Recommended Daily Dose:  0.211 Skin Sensitization:  0.71
Carcinogencity:  0.63 Eye Corrosion:  0.025
Eye Irritation:  0.988 Respiratory Toxicity:  0.326
Drug-induced Neurotoxicity:  0.223 Ototoxicity:  0.077
Hematotoxicity:  0.013 Drug-induced Nephrotoxicity:  0.065
Genotoxicity:  0.012 RPMI-8226 Immunitoxicity:  0.09
A549 Cytotoxicity:  0.092 Hek293 Cytotoxicity:  0.408
BCF:   0.942
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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:   4.098
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.781
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.583
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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
NPO6984 Brickellia veronicaefolia Species Asteraceae Eukaryota essential oil n.a. n.a. PMID[16933870]
NPO6984 Brickellia veronicaefolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6984 Brickellia veronicaefolia Species Asteraceae 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
NPT548 Tissue Ileum Cavia porcellus IC50 = 1490.0 nM PMID[20815366]

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 NPC4164 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
0.6364 Remote Similarity NPC45104
0.6136 Remote Similarity NPC233282
0.5714 Remote Similarity NPC12694
0.561 Remote Similarity NPC128825

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC4164 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
0.561 Remote Similarity NPD9493 Phase 4

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