Natural Product: NPC131718

Natural Product IDNPC131718
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Sid24824100
IUPAC Name 1H-indole-3-carboxamide
Synonyms 3-Indoleacetamide; Indole-3-Acetamide
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL379099
PubChem CID 2192542
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0002013] Indolecarboxylic acids and derivatives
          • [CHEMONTID:0002014] Indolecarboxamides 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 LSGKMZLPZFPAIN-UHFFFAOYSA-N
Standard InCHI InChI=1S/C9H8N2O/c10-9(12)7-5-11-8-4-2-1-3-6(7)8/h1-5,11H,(H2,10,12)
SMILES OC(=N)c1c[nH]c2c1cccc2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   160.06 Volume:   164.709
?
Van der Waals volume.
Dense:   0.972 LogP:   1.116
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.288
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.867
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   11.0
TPSA:   59.87
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.434 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.225 Fsp3:   0.0
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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.075 Fluc inhibitor:   0.013
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.273
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.077
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.167 Promiscuous compounds:   0.861

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.836 MDCK Permeability:   -5.189
Pgp-inhibitor:   0.013 Pgp-substrate:   0.837
PAMPA:   0.876
?
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):   0.073
20% Bioavailability (F20%):   0.222 30% Bioavailability (F30%):   0.652
50% Bioavailability (F50%):   0.541

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.135 MRP1:   0.546
Plasma Protein Binding (PPB):   57.274% Volume Distribution (VD):   0.265
Fu: 38.761%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.374
OATP1B3 inhibitor:   0.677 BCRP inhibitor:   0.077
BSEP inhibitor:   0.166

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.306 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.528 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.225
HLM stability:   0.321
?
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):  1.364 Half-life (T1/2):  1.458

ADMET: Toxicity

hERG Blockers:  0.079 hERG Blockers (10um):  0.202
Human Hepatotoxicity (H-HT):  0.941 Drug-induced Liver Injury (DILI):  0.696
AMES Toxicity:  0.491 Rat Oral Acute Toxicity:  0.638
Maximum Recommended Daily Dose:  0.217 Skin Sensitization:  0.849
Carcinogencity:  0.856 Eye Corrosion:  0.013
Eye Irritation:  0.961 Respiratory Toxicity:  0.906
Drug-induced Neurotoxicity:  0.763 Ototoxicity:  0.268
Hematotoxicity:  0.327 Drug-induced Nephrotoxicity:  0.541
Genotoxicity:  0.921 RPMI-8226 Immunitoxicity:  0.019
A549 Cytotoxicity:  0.077 Hek293 Cytotoxicity:  0.149
BCF:   0.265
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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:   2.71
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.835
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.292
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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
NPO31050 Isatis indigotica Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[11678654]
NPO31050 Isatis indigotica Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[15787451]
NPO31050 Isatis indigotica Species Brassicaceae Eukaryota Roots Anhui, China n.a. PMID[22694318]
NPO31050 Isatis indigotica Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31050 Isatis indigotica Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31050 Isatis indigotica Species Brassicaceae 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
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens Potency n.a. 1636.0 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 29.1 nM PubChem BioAssay data set
NPT94 Individual protein Aldehyde dehydrogenase 1A1 Homo sapiens Potency = 39810.7 nM Open TG-GATES in vivo data: Organ Weight
NPT524 Individual protein Serine-protein kinase ATM Homo sapiens Potency = 631.0 nM PMID[20550123]
NPT536 Nucleic acid microRNA 21 Homo sapiens Potency = 26121.6 nM PMID[17665952]
NPT56 Individual protein Beta-lactamase AmpC Escherichia coli K-12 Potency = 14125.4 nM Open TG-GATES in vivo data: Hematology
NPT49 Individual protein DNA-(apurinic or apyrimidinic site) lyase Homo sapiens Potency n.a. 50118.7 nM PMID[18710917]

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. 1852.6 nM PubChem BioAssay data set
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 3.3 nM PMID[20570625]
NPT2 Others Unspecified n.a. Potency = 461.1 nM PMID[20876370]

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 NPC131718 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
0.5909 Remote Similarity NPC159856
0.5897 Remote Similarity NPC102423
0.5676 Remote Similarity NPC261195
0.5641 Remote Similarity NPC216643
0.5641 Remote Similarity NPC288838
0.5641 Remote Similarity NPC601214
0.55 Remote Similarity NPC105127
0.55 Remote Similarity NPC53947
0.55 Remote Similarity NPC300149
0.55 Remote Similarity NPC42372
0.55 Remote Similarity NPC230002
0.5476 Remote Similarity NPC230869
0.5349 Remote Similarity NPC72435
0.5349 Remote Similarity NPC604154
0.5238 Remote Similarity NPC96102
0.5227 Remote Similarity NPC154339
0.5116 Remote Similarity NPC138370
0.5116 Remote Similarity NPC279081
0.5111 Remote Similarity NPC111275

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC131718 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
0.5238 Remote Similarity NPD198 Clinical (unspecified phase)

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