Natural Product: NPC476460

Natural Product IDNPC476460
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Sid49676895
IUPAC Name 2-(1H-indol-3-yl)-N-[2-(1H-indol-3-yl)ethyl]-2-oxoacetamide
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL70704
PubChem CID 5196982
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0002497] Indoles
          • [CHEMONTID:0004196] 3-alkylindoles

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 KBMAPSVVTDUGNY-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H17N3O2/c24-19(16-12-23-18-8-4-2-6-15(16)18)20(25)21-10-9-13-11-22-17-7-3-1-5-14(13)17/h1-8,11-12,22-23H,9-10H2,(H,21,25)
SMILES C1=CC=C2C(=C1)C(=CN2)CCNC(=O)C(=O)C3=CNC4=CC=CC=C43

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   331.13 Volume:   344.456
?
Van der Waals volume.
Dense:   0.961 LogP:   2.76
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.599
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.6
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   22.0
TPSA:   77.75
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.388 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.147 Fsp3:   0.1
MCE-18:   20.0
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.973 Fluc inhibitor:   0.769
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.129
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.62
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.003 Promiscuous compounds:   0.796

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.151 MDCK Permeability:   -4.688
Pgp-inhibitor:   0.927 Pgp-substrate:   0.212
PAMPA:   0.044
?
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):   0.014
20% Bioavailability (F20%):   0.021 30% Bioavailability (F30%):   0.329
50% Bioavailability (F50%):   0.687

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.3 MRP1:   0.036
Plasma Protein Binding (PPB):   96.751% Volume Distribution (VD):   -0.174
Fu: 3.243%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.769
OATP1B3 inhibitor:   0.798 BCRP inhibitor:   0.472
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.235 CYP1A2-substrate:   0.997
CYP2C19-inhibitor:   0.011 CYP2C19-substrate:   0.964
CYP2C9-inhibitor:   0.973 CYP2C9-substrate:   0.996
CYP2D6-inhibitor:   0.986 CYP2D6-substrate:   0.911
CYP3A4-inhibitor:   0.026 CYP3A4-substrate:   0.005
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.858
?
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):  7.147 Half-life (T1/2):  0.396

ADMET: Toxicity

hERG Blockers:  0.234 hERG Blockers (10um):  0.537
Human Hepatotoxicity (H-HT):  0.622 Drug-induced Liver Injury (DILI):  0.559
AMES Toxicity:  0.554 Rat Oral Acute Toxicity:  0.553
Maximum Recommended Daily Dose:  0.672 Skin Sensitization:  0.175
Carcinogencity:  0.4 Eye Corrosion:  0.0
Eye Irritation:  0.74 Respiratory Toxicity:  0.533
Drug-induced Neurotoxicity:  0.755 Ototoxicity:  0.495
Hematotoxicity:  0.372 Drug-induced Nephrotoxicity:  0.384
Genotoxicity:  0.949 RPMI-8226 Immunitoxicity:  0.023
A549 Cytotoxicity:  0.175 Hek293 Cytotoxicity:  0.173
BCF:   1.492
?
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:   4.0
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.397
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.914
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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
NPO33091 marine sp. Species n.a. n.a. n.a. n.a. n.a. PMID[17548194]

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
NPT135 Individual protein Chromobox protein homolog 1 Homo sapiens Potency n.a. 79432.8 nM PMID[22037378]
NPT154 Individual protein Mothers against decapentaplegic homolog 3 Homo sapiens Potency n.a. 31622.8 nM DOI[10.6019/CHEMBL1201861]
NPT101 Individual protein Glucagon-like peptide 1 receptor Homo sapiens Potency n.a. 4466.8 nM PMID[8277321]
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 14125.4 nM PMID[22750009]
NPT477 Individual protein DNA dC->dU-editing enzyme APOBEC-3G Homo sapiens Potency n.a. 19952.6 nM PMID[18053715]
NPT1325 Protein complex GABA-A receptor; anion channel Bos taurus Inhibition = 83.0 % PMID[11412982]
NPT1325 Protein complex GABA-A receptor; anion channel Bos taurus Ki = 1500.0 nM PMID[18847246]
NPT1325 Protein complex GABA-A receptor; anion channel Bos taurus Ratio = 1.0 n.a. PMID[11412982]
NPT63 Individual protein Bromodomain adjacent to zinc finger domain protein 2B Homo sapiens Potency n.a. 44668.4 nM DrugMatrix in vitro pharmacology data
NPT478 Individual protein Ataxin-2 Homo sapiens Potency n.a. 4466.8 nM Open TG-GATES in vivo data: Biochemistry
NPT5 Individual protein Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Homo sapiens Potency n.a. 44668.4 nM PMID[31473]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT65 Cell line HepG2 Homo sapiens Potency n.a. 15848.9 nM PMID[23398362]
NPT165 Cell line HeLa Homo sapiens IC50 = 48850.0 nM PMID[21070010]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 = 48700.0 nM PMID[20071056]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 18526.0 nM PMID[18725441]
NPT633 Organism Leishmania donovani Leishmania donovani Inhibition = 100.0 % PMID[26200396]
NPT633 Organism Leishmania donovani Leishmania donovani Inhibition = 97.72 % PMID[19548690]
NPT2911 Organism Pseudomonas putida Pseudomonas putida MIC = 50.0 ug.mL-1 PMID[21534539]
NPT2911 Organism Pseudomonas putida Pseudomonas putida IZ = 14.0 mm PMID[23145884]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 50.0 ug.mL-1 PubChem BioAssay data set
NPT79 Organism Bacillus subtilis Bacillus subtilis IZ = 15.0 mm PMID[24507923]
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae MIC = 100.0 ug.mL-1 PMID[8411013]
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae IZ = 14.0 mm PMID[8411013]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 71510.0 nM PMID[27173802]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 38450.0 nM PMID[27173802]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 63950.0 nM PMID[27173802]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 50.0 ug.mL-1 PMID[22283451]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus IZ = 15.0 mm PMID[16933872]
NPT19 Organism Escherichia coli Escherichia coli IZ = 15.0 mm PMID[19969457]
NPT19 Organism Escherichia coli Escherichia coli MIC = 50.0 ug.mL-1 PMID[19969457]
NPT2 Others Unspecified n.a. AC50 = 1482.0 nM DrugMatrix in vitro pharmacology data
NPT2 Others Unspecified n.a. Potency n.a. 6309.6 nM PMID[19654408]
NPT2 Others Unspecified n.a. AC50 = 6750.0 nM PMID[11473413]

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 NPC476460 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
0.7288 Intermediate Similarity NPC604339
0.7037 Intermediate Similarity NPC608269
0.6441 Remote Similarity NPC469760
0.6441 Remote Similarity NPC469786
0.6333 Remote Similarity NPC605381
0.629 Remote Similarity NPC469762
0.5758 Remote Similarity NPC477003
0.5645 Remote Similarity NPC99939
0.56 Remote Similarity NPC300149
0.55 Remote Similarity NPC314002
0.5455 Remote Similarity NPC310665
0.537 Remote Similarity NPC154339
0.5246 Remote Similarity NPC606242
0.5098 Remote Similarity NPC601214
0.5082 Remote Similarity NPC602373

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC476460 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