Natural Product: NPC245259

Natural Product IDNPC245259
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Ethyl 3-(Phenethylcarbamoyl)Propylcarbamate
IUPAC Name ethyl N-[4-oxo-4-(2-phenylethylamino)butyl]carbamate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3086767
PubChem CID 72946782
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000264] Organic acids and derivatives
      • [CHEMONTID:0000265] Carboxylic acids and derivatives
        • [CHEMONTID:0000013] Amino acids, peptides, and analogues
          • [CHEMONTID:0000347] Amino acids and derivatives
            • [CHEMONTID:0001880] Gamma amino acids and derivatives

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 HTOYBIILVCHURC-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H22N2O3/c1-2-20-15(19)17-11-6-9-14(18)16-12-10-13-7-4-3-5-8-13/h3-5,7-8H,2,6,9-12H2,1H3,(H,16,18)(H,17,19)
SMILES CCOC(=NCCCC(=NCCc1ccccc1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   278.16 Volume:   294.622
?
Van der Waals volume.
Dense:   0.944 LogP:   2.368
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.064
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.748
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   8.0
TPSA:   74.41
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.436 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.675 Fsp3:   0.467
MCE-18:   6.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.092 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.04
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.296
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.028 Promiscuous compounds:   0.452

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.472 MDCK Permeability:   -4.601
Pgp-inhibitor:   0.906 Pgp-substrate:   0.236
PAMPA:   0.277
?
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):   0.038
20% Bioavailability (F20%):   0.75 30% Bioavailability (F30%):   0.762
50% Bioavailability (F50%):   0.831

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.057 MRP1:   0.61
Plasma Protein Binding (PPB):   87.59% Volume Distribution (VD):   0.088
Fu: 9.087%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.913
OATP1B3 inhibitor:   0.702 BCRP inhibitor:   0.025
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.678 CYP1A2-substrate:   0.011
CYP2C19-inhibitor:   0.982 CYP2C19-substrate:   0.275
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.009
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.003
CYP3A4-inhibitor:   0.993 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.007 CYP2C8-inhibitor:   0.256
HLM stability:   0.107
?
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):  7.973 Half-life (T1/2):  0.494

ADMET: Toxicity

hERG Blockers:  0.158 hERG Blockers (10um):  0.307
Human Hepatotoxicity (H-HT):  0.94 Drug-induced Liver Injury (DILI):  0.706
AMES Toxicity:  0.719 Rat Oral Acute Toxicity:  0.462
Maximum Recommended Daily Dose:  0.383 Skin Sensitization:  0.999
Carcinogencity:  0.833 Eye Corrosion:  0.0
Eye Irritation:  0.202 Respiratory Toxicity:  0.752
Drug-induced Neurotoxicity:  0.165 Ototoxicity:  0.565
Hematotoxicity:  0.267 Drug-induced Nephrotoxicity:  0.715
Genotoxicity:  0.417 RPMI-8226 Immunitoxicity:  0.003
A549 Cytotoxicity:  0.005 Hek293 Cytotoxicity:  0.064
BCF:   0.218
?
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:   2.902
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.154
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.388
?
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
NPO33200 symploca sp. Species Microcoleaceae Bacteria n.a. n.a. n.a. PMID[12350160]
NPO33200 symploca sp. Species Microcoleaceae Bacteria n.a. n.a. n.a. PMID[12762794]
NPO33200 symploca sp. Species Microcoleaceae Bacteria n.a. Sunday Island, Papua New Guinea n.a. PMID[18163584]
NPO33200 symploca sp. Species Microcoleaceae Bacteria n.a. Papua New Guinea n.a. PMID[20687534]
NPO33200 symploca sp. Species Microcoleaceae Bacteria n.a. Panamanian n.a. PMID[24164245]
NPO33200 symploca sp. Species Microcoleaceae Bacteria n.a. n.a. n.a. PMID[24588245]
NPO33200 symploca sp. Species Microcoleaceae Bacteria n.a. n.a. n.a. PMID[28055219]
NPO33200 symploca sp. Species Microcoleaceae Bacteria n.a. n.a. n.a. PMID[29808677]

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
NPT4345 Protein complex Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) Homo sapiens Inhibition = 89.0 % PMID[27614919]
NPT689 Individual protein Histone deacetylase 5 Homo sapiens Inhibition = 66.0 % PMID[27614919]
NPT4345 Protein complex Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) Homo sapiens Inhibition = 10.0 % PMID[27614919]
NPT689 Individual protein Histone deacetylase 5 Homo sapiens Inhibition = 0.0 % PMID[27614919]
NPT4345 Protein complex Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) Homo sapiens IC50 = 5000.0 nM PMID[27614919]
NPT689 Individual protein Histone deacetylase 5 Homo sapiens IC50 = 5000.0 nM PMID[27614919]
NPT692 Individual protein Histone deacetylase 6 Homo sapiens IC50 = 433.0 nM Open TG-GATES in vivo data: Biochemistry
NPT692 Individual protein Histone deacetylase 6 Homo sapiens IC50 = 433.5 nM PubChem BioAssay data set
NPT688 Individual protein Histone deacetylase 4 Homo sapiens IC50 > 1000.0 nM PMID[25871540]
NPT685 Individual protein Histone deacetylase 2 Homo sapiens IC50 = 0.112 nM PMID[25871540]
NPT685 Individual protein Histone deacetylase 2 Homo sapiens IC50 = 0.119 nM PMID[25871540]
NPT685 Individual protein Histone deacetylase 2 Homo sapiens IC50 > 1000.0 nM PMID[27614919]
NPT684 Individual protein Histone deacetylase 1 Homo sapiens Inhibition = 90.0 % PMID[27614919]
NPT685 Individual protein Histone deacetylase 2 Homo sapiens Inhibition = 80.0 % PMID[27614919]
NPT688 Individual protein Histone deacetylase 4 Homo sapiens Inhibition = 86.0 % PMID[27614919]
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = 83.0 % PMID[27614919]
NPT690 Individual protein Histone deacetylase 7 Homo sapiens Inhibition = 74.0 % PMID[27614919]
NPT691 Individual protein Histone deacetylase 9 Homo sapiens Inhibition = 75.0 % PMID[27614919]
NPT5649 Individual protein Histone deacetylase 10 Homo sapiens Inhibition = 93.0 % PMID[27614919]
NPT684 Individual protein Histone deacetylase 1 Homo sapiens Inhibition = 7.0 % PMID[27614919]
NPT685 Individual protein Histone deacetylase 2 Homo sapiens Inhibition = 6.0 % PMID[27614919]
NPT688 Individual protein Histone deacetylase 4 Homo sapiens Inhibition = 4.0 % PMID[27614919]
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = 16.0 % PMID[27614919]
NPT690 Individual protein Histone deacetylase 7 Homo sapiens Inhibition = 0.0 % PMID[27614919]
NPT691 Individual protein Histone deacetylase 9 Homo sapiens Inhibition = 10.0 % PMID[27614919]
NPT5649 Individual protein Histone deacetylase 10 Homo sapiens Inhibition = 16.0 % PMID[27614919]
NPT684 Individual protein Histone deacetylase 1 Homo sapiens IC50 = 5000.0 nM PMID[27614919]
NPT685 Individual protein Histone deacetylase 2 Homo sapiens IC50 = 5000.0 nM PMID[27614919]
NPT688 Individual protein Histone deacetylase 4 Homo sapiens IC50 = 5000.0 nM PMID[27614919]
NPT690 Individual protein Histone deacetylase 7 Homo sapiens IC50 = 5000.0 nM PMID[27614919]
NPT691 Individual protein Histone deacetylase 9 Homo sapiens IC50 = 5000.0 nM PMID[27614919]
NPT5649 Individual protein Histone deacetylase 10 Homo sapiens IC50 = 5000.0 nM PMID[27614919]
NPT692 Individual protein Histone deacetylase 6 Homo sapiens IC50 = 5000.0 nM PMID[27614919]
NPT20556 Single protein Replicase polyprotein 1ab Severe acute respiratory syndrome coronavirus 2 Inhibition = 12.39 % DOI[10.6019/CHEMBL4495564]
NPT687 Individual protein Histone deacetylase 8 Homo sapiens Inhibition = 73.0 % PMID[27614919]
NPT5648 Individual protein Histone deacetylase 11 Homo sapiens Inhibition = 78.0 % PMID[27614919]
NPT687 Individual protein Histone deacetylase 8 Homo sapiens Inhibition = 5.0 % PMID[27614919]
NPT5648 Individual protein Histone deacetylase 11 Homo sapiens Inhibition = 0.0 % PMID[27614919]
NPT687 Individual protein Histone deacetylase 8 Homo sapiens IC50 = 5000.0 nM PMID[27614919]
NPT5648 Individual protein Histone deacetylase 11 Homo sapiens IC50 = 5000.0 nM PMID[27614919]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT393 Cell line HCT-116 Homo sapiens Ratio IC50 = 20.0 n.a. PMID[24164245]
NPT708 Cell line HuT78 Homo sapiens GI50 = 1300.0 nM PMID[20192237]
NPT708 Cell line HuT78 Homo sapiens GI50 = 1400.0 nM PMID[25333996]
NPT393 Cell line HCT-116 Homo sapiens GI50 = 28300.0 nM PMID[20666364]
NPT393 Cell line HCT-116 Homo sapiens GI50 = 29400.0 nM Open TG-GATES in vivo data: Biochemistry
NPT393 Cell line HCT-116 Homo sapiens IC50 > 50000.0 nM PMID[29100734]
NPT927 Cell line PBMC Homo sapiens GI50 > 50000.0 nM PMID[27614919]
NPT112 Cell line MOLT-4 Homo sapiens GI50 > 50000.0 nM PMID[27614919]
NPT708 Cell line HuT78 Homo sapiens GI50 > 50000.0 nM PMID[27614919]
NPT82 Cell line MDA-MB-231 Homo sapiens GI50 > 50000.0 nM PMID[27614919]
NPT83 Cell line MCF7 Homo sapiens GI50 > 50000.0 nM PMID[27614919]
NPT393 Cell line HCT-116 Homo sapiens GI50 > 50000.0 nM PMID[27614919]
NPT393 Cell line HCT-116 Homo sapiens GI50 = 17200.0 nM PMID[27614919]
NPT708 Cell line HuT78 Homo sapiens GI50 = 36000.0 nM PMID[27614919]
NPT112 Cell line MOLT-4 Homo sapiens GI50 = 7800.0 nM PMID[27614919]
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Inhibition = -0.05 % DOI[10.6019/CHEMBL4495565]
NPT2254 Organism Schistosoma mansoni Schistosoma mansoni In vitro activity n.a. n.a. n.a. Using ChEMBL to complement schistosome drug discovery
NPT2 Others Unspecified n.a. Ratio IC50 = 3866.0 n.a. Open TG-GATES in vivo data: Biochemistry
NPT2 Others Unspecified n.a. Ratio IC50 = 3647.0 n.a. Open TG-GATES in vivo data: Biochemistry

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 NPC245259 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
0.5273 Remote Similarity NPC489324
0.5179 Remote Similarity NPC486087
0.5088 Remote Similarity NPC486088

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC245259 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