Natural Product: NPC43275

Natural Product IDNPC43275
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 N-[2-(4-Methoxyphenyl)Ethyl]Benzamide
IUPAC Name N-[2-(4-methoxyphenyl)ethyl]benzamide
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1497400
PubChem CID 3083797
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000176] Benzoic acids and derivatives
          • [CHEMONTID:0000178] Benzamides

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 RAOWOXJDGFFKKD-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H17NO2/c1-19-15-9-7-13(8-10-15)11-12-17-16(18)14-5-3-2-4-6-14/h2-10H,11-12H2,1H3,(H,17,18)
SMILES COc1ccc(cc1)CCN=C(c1ccccc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   255.13 Volume:   278.301
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Van der Waals volume.
Dense:   0.917 LogP:   3.233
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.686
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.633
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   13.0
TPSA:   41.82
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.658 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.847 Fsp3:   0.188
MCE-18:   10.0
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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:   0.393 Fluc inhibitor:   0.704
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.056
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.714
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.035 Promiscuous compounds:   0.189

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.63 MDCK Permeability:   -4.509
Pgp-inhibitor:   0.111 Pgp-substrate:   0.975
PAMPA:   0.32
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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):   0.203
20% Bioavailability (F20%):   0.179 30% Bioavailability (F30%):   0.118
50% Bioavailability (F50%):   0.855

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.078 MRP1:   0.272
Plasma Protein Binding (PPB):   98.14% Volume Distribution (VD):   0.07
Fu: 0.925%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.852
OATP1B3 inhibitor:   0.266 BCRP inhibitor:   0.21
BSEP inhibitor:   0.885

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.715
CYP2C19-inhibitor:   0.981 CYP2C19-substrate:   0.907
CYP2C9-inhibitor:   0.975 CYP2C9-substrate:   0.923
CYP2D6-inhibitor:   0.991 CYP2D6-substrate:   0.781
CYP3A4-inhibitor:   0.919 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   0.993
HLM stability:   0.992
?
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):  7.444 Half-life (T1/2):  0.315

ADMET: Toxicity

hERG Blockers:  0.221 hERG Blockers (10um):  0.274
Human Hepatotoxicity (H-HT):  0.795 Drug-induced Liver Injury (DILI):  0.674
AMES Toxicity:  0.401 Rat Oral Acute Toxicity:  0.296
Maximum Recommended Daily Dose:  0.481 Skin Sensitization:  0.632
Carcinogencity:  0.355 Eye Corrosion:  0.001
Eye Irritation:  0.801 Respiratory Toxicity:  0.822
Drug-induced Neurotoxicity:  0.537 Ototoxicity:  0.656
Hematotoxicity:  0.433 Drug-induced Nephrotoxicity:  0.815
Genotoxicity:  0.502 RPMI-8226 Immunitoxicity:  0.011
A549 Cytotoxicity:  0.062 Hek293 Cytotoxicity:  0.203
BCF:   0.741
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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:   3.398
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.564
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.11
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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
NPO7317 Citrus aurantium Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[10606602]
NPO587 Saussurea stella Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[17844995]
NPO7317 Citrus aurantium Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[35268681]
NPO7317 Citrus aurantium Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[38308284]
NPO7317 Citrus aurantium Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[39410132]
NPO9593 Anoectochilus koshunensis Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO371 Courbonia virgata n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO11564 Ruditapes philippinarum Species Veneridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7317 Citrus aurantium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7317 Citrus aurantium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2017 Poa sphondylodes Species Poaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2017 Poa sphondylodes Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7317 Citrus aurantium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2017 Poa sphondylodes Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7317 Citrus aurantium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7317 Citrus aurantium Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO371 Courbonia virgata n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO11564 Ruditapes philippinarum Species Veneridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO587 Saussurea stella Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9119 Pterocladiella capillacea Species Gelidiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21916.1 Herbertus juniperoideus subsp. acanthelius Subspecies Herbertaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9593 Anoectochilus koshunensis Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2017 Poa sphondylodes Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7317 Citrus aurantium Species Rutaceae 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
NPT484 Individual protein Luciferin 4-monooxygenase Photinus pyralis Potency n.a. 26854.5 nM PubChem BioAssay data set
NPT8 Individual protein DNA polymerase iota Homo sapiens Potency n.a. 89125.1 nM PubChem BioAssay data set
NPT536 Nucleic acid microRNA 21 Homo sapiens Potency = 13091.8 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 6573.3 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 11220.2 nM PubChem BioAssay data set

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 NPC43275 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
0.7568 Intermediate Similarity NPC311723
0.7174 Intermediate Similarity NPC47670
0.6364 Remote Similarity NPC153690
0.587 Remote Similarity NPC29477
0.58 Remote Similarity NPC254610
0.5593 Remote Similarity NPC480457
0.541 Remote Similarity NPC480460
0.541 Remote Similarity NPC480456
0.5077 Remote Similarity NPC480458

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC43275 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