Natural Product: NPC230002

Natural Product IDNPC230002
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Indole-3-Carbonitrile
IUPAC Name 1H-indole-3-carbonitrile
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL46724
PubChem CID 230282
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0002497] Indoles

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 CHIFTAQVXHNVRW-UHFFFAOYSA-N
Standard InCHI InChI=1S/C9H6N2/c10-5-7-6-11-9-4-2-1-3-8(7)9/h1-4,6,11H
SMILES N#Cc1c[nH]c2c1cccc2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   142.05 Volume:   153.282
?
Van der Waals volume.
Dense:   0.927 LogP:   2.247
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.32
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.478
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The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   11.0
TPSA:   39.58
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.6 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.056 Fsp3:   0.0
MCE-18:   9.0
?
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:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.077 Fluc inhibitor:   0.026
?
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:   0.047
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.785 Promiscuous compounds:   0.838

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.507 MDCK Permeability:   -4.673
Pgp-inhibitor:   0.711 Pgp-substrate:   0.002
PAMPA:   0.202
?
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):   0.049
20% Bioavailability (F20%):   0.023 30% Bioavailability (F30%):   0.128
50% Bioavailability (F50%):   0.615

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.073 MRP1:   0.194
Plasma Protein Binding (PPB):   88.93% Volume Distribution (VD):   0.116
Fu: 12.385%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.359
OATP1B3 inhibitor:   0.947 BCRP inhibitor:   0.059
BSEP inhibitor:   0.99

ADMET: Metabolism

CYP1A2-inhibitor:   0.345 CYP1A2-substrate:   0.993
CYP2C19-inhibitor:   0.067 CYP2C19-substrate:   0.812
CYP2C9-inhibitor:   0.75 CYP2C9-substrate:   0.078
CYP2D6-inhibitor:   0.961 CYP2D6-substrate:   0.335
CYP3A4-inhibitor:   0.436 CYP3A4-substrate:   0.067
CYP2B6-substrate:   0.323 CYP2C8-inhibitor:   0.776
HLM stability:   0.53
?
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):  6.551 Half-life (T1/2):  1.208

ADMET: Toxicity

hERG Blockers:  0.154 hERG Blockers (10um):  0.559
Human Hepatotoxicity (H-HT):  0.626 Drug-induced Liver Injury (DILI):  0.427
AMES Toxicity:  0.598 Rat Oral Acute Toxicity:  0.572
Maximum Recommended Daily Dose:  0.544 Skin Sensitization:  0.407
Carcinogencity:  0.689 Eye Corrosion:  0.642
Eye Irritation:  0.985 Respiratory Toxicity:  0.787
Drug-induced Neurotoxicity:  0.688 Ototoxicity:  0.306
Hematotoxicity:  0.344 Drug-induced Nephrotoxicity:  0.383
Genotoxicity:  0.412 RPMI-8226 Immunitoxicity:  0.048
A549 Cytotoxicity:  0.074 Hek293 Cytotoxicity:  0.205
BCF:   0.522
?
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:   2.937
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.25
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.531
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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
NPO1099 Capparis spinosa Species Capparaceae Eukaryota aerial parts and buds Cagliari, Sardinia 2012-FEB PMID[22769561]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota Flower n.a. n.a. Database[FooDB]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota n.a. n.a. Database[FooDB]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota n.a. n.a. Database[FooDB]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1099 Capparis spinosa Species Capparaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1099 Capparis spinosa Species Capparaceae 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
NPT2817 Individual protein Inosine-5'-monophosphate dehydrogenase 2 Homo sapiens IC50 = 20900.0 nM PMID[8133298]
NPT5069 Individual protein Tryptophan 2,3-dioxygenase Mus musculus IC50 > 80000.0 nM PMID[19061390]
NPT5340 Protein family Inosine-5'-monophosphate dehydrogenase (IMPDH) Homo sapiens IC50 = 32000.0 nM PMID[20145089]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT450 Organism Meloidogyne incognita Meloidogyne incognita EC50 = 68.9 ug.mL-1 PMID[20949916]
NPT450 Organism Meloidogyne incognita Meloidogyne incognita EC50 > 250.0 ug.mL-1 PMID[21621880]

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 NPC230002 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
0.6216 Remote Similarity NPC300149
0.6216 Remote Similarity NPC42372
0.6154 Remote Similarity NPC279081
0.6 Remote Similarity NPC261195
0.5946 Remote Similarity NPC216643
0.5946 Remote Similarity NPC288838
0.5946 Remote Similarity NPC601214
0.5789 Remote Similarity NPC105127
0.5789 Remote Similarity NPC53947
0.5789 Remote Similarity NPC102423
0.575 Remote Similarity NPC138370
0.561 Remote Similarity NPC72435
0.5581 Remote Similarity NPC67288
0.5581 Remote Similarity NPC310665
0.55 Remote Similarity NPC131718
0.55 Remote Similarity NPC96102
0.5476 Remote Similarity NPC154339
0.5366 Remote Similarity NPC230869
0.5349 Remote Similarity NPC111275
0.5238 Remote Similarity NPC29886
0.5238 Remote Similarity NPC601179
0.5238 Remote Similarity NPC604154
0.5227 Remote Similarity NPC605863
0.5217 Remote Similarity NPC600736
0.5217 Remote Similarity NPC605085
0.5116 Remote Similarity NPC84911
0.5116 Remote Similarity NPC608908
0.5111 Remote Similarity NPC603879
0.5106 Remote Similarity NPC470823

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC230002 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
0.55 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