Natural Product: NPC66775

Natural Product IDNPC66775
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Phenylisothiocyanate
IUPAC Name isothiocyanatobenzene
Synonyms Isothiocyanato-Benzene; Isothiocyanatobenzene; Phenyl Isothiocyanate
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL309036
PubChem CID 7673
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted 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 QKFJKGMPGYROCL-UHFFFAOYSA-N
Standard InCHI InChI=1S/C7H5NS/c9-6-8-7-4-2-1-3-5-7/h1-5H
SMILES c1ccc(cc1)N=C=S

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   135.01 Volume:   137.395
?
Van der Waals volume.
Dense:   0.983 LogP:   3.255
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.065
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.986
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   8.0
TPSA:   12.36
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.425 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.305 Fsp3:   0.0
MCE-18:   4.0
?
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:   Accepted BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.11 Fluc inhibitor:   0.571
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.025
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.018
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   1.0 Promiscuous compounds:   0.098

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.414 MDCK Permeability:   -4.537
Pgp-inhibitor:   0.917 Pgp-substrate:   0.001
PAMPA:   0.052
?
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):   0.0
20% Bioavailability (F20%):   0.004 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.062

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.379 MRP1:   0.014
Plasma Protein Binding (PPB):   96.585% Volume Distribution (VD):   -0.125
Fu: 2.704%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.016
OATP1B3 inhibitor:   0.538 BCRP inhibitor:   0.0
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.032 CYP1A2-substrate:   0.008
CYP2C19-inhibitor:   0.064 CYP2C19-substrate:   0.269
CYP2C9-inhibitor:   0.213 CYP2C9-substrate:   0.221
CYP2D6-inhibitor:   0.006 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.889 CYP3A4-substrate:   0.664
CYP2B6-substrate:   0.018 CYP2C8-inhibitor:   0.997
HLM stability:   0.036
?
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):  6.688 Half-life (T1/2):  1.253

ADMET: Toxicity

hERG Blockers:  0.026 hERG Blockers (10um):  0.922
Human Hepatotoxicity (H-HT):  0.068 Drug-induced Liver Injury (DILI):  0.998
AMES Toxicity:  0.813 Rat Oral Acute Toxicity:  0.93
Maximum Recommended Daily Dose:  0.796 Skin Sensitization:  0.996
Carcinogencity:  0.689 Eye Corrosion:  1.0
Eye Irritation:  1.0 Respiratory Toxicity:  1.0
Drug-induced Neurotoxicity:  0.403 Ototoxicity:  0.02
Hematotoxicity:  0.025 Drug-induced Nephrotoxicity:  0.061
Genotoxicity:  0.03 RPMI-8226 Immunitoxicity:  0.056
A549 Cytotoxicity:  0.005 Hek293 Cytotoxicity:  0.502
BCF:   1.578
?
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:   4.314
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.235
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.325
?
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
NPO20712 Panax quinquefolius Species Araliaceae Eukaryota n.a. n.a. n.a. PMID[ 12877918]
NPO20712 Panax quinquefolius Species Araliaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.jarmap.2018.11.004]
NPO29007 Brassica juncea Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1155/2014/726070]
NPO20712 Panax quinquefolius Species Araliaceae Eukaryota leaves and stems n.a. n.a. PMID[25442304]
NPO29007 Brassica juncea Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[25700090]
NPO20712 Panax quinquefolius Species Araliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29007 Brassica juncea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29812 Panax quinquefolium Species Araliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29007 Brassica juncea Species Brassicaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO29007 Brassica juncea Species Brassicaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO29007 Brassica juncea Species Brassicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO29812 Panax quinquefolium Species Araliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29007 Brassica juncea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29007 Brassica juncea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20712 Panax quinquefolius Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29812 Panax quinquefolium Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29007 Brassica juncea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29007 Brassica juncea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20712 Panax quinquefolius Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29007 Brassica juncea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20712 Panax quinquefolius Species Araliaceae 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
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens Potency n.a. 56260.4 nM PubChem BioAssay data set
NPT1250 Individual protein Macrophage migration inhibitory factor Homo sapiens IC50 = 11000.0 nM PMID[25743213]
NPT214 Individual protein Cathepsin B Homo sapiens Activity = 100.0 % PMID[30321804]
NPT214 Individual protein Cathepsin B Homo sapiens Activity = 98.0 % PMID[30321804]
NPT68 Individual protein Aldose reductase Rattus norvegicus Inhibition = 34.0 % PMID[3097318]
NPT68 Individual protein Aldose reductase Rattus norvegicus Inhibition = 5.0 % PMID[3097318]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT65 Cell line HepG2 Homo sapiens IC50 = 984.0 nM PMID[30594028]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum Inhibition = 100.0 % PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum Inhibition = 68.3 % PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum Inhibition = 61.7 % PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum Inhibition = 52.5 % PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum Inhibition = 12.5 % PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum EC50 = 192000.0 nM PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum EC50 = 802000.0 nM PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum EC50 = 134000.0 nM PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum GI = 100.0 % PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum Inhibition = 46.7 % PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum Inhibition = 13.3 % PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum Inhibition = 6.7 % PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum GI = 65.5 % PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum GI = 23.7 % PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum GI = 5.0 % PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum GI = 74.2 % PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum GI = 70.0 % PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum GI = 42.8 % PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum GI = 20.8 % PMID[21370393]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum Inhibition = 85.0 % PMID[21370393]
NPT2 Others Unspecified n.a. Potency n.a. 1122.5 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 28197 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 56706.8 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 70827.7 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 50540 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 35497.9 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 50142.2 nM PubChem BioAssay data set

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT449 Organism Meloidogyne javanica Meloidogyne javanica mortality = 58.25 % DOI[10.1016/j.cropro.2010.09.004]
NPT449 Organism Meloidogyne javanica Meloidogyne javanica mortality = 25.63 % DOI[10.1016/j.cropro.2010.09.004]





 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
- Rattus norvegicus BMDL (1SD ADJ) = 1.7 mg/kg-day ToxVal
- Mus musculus LD50 = 3.130947781 mg/kg TOXRIC
- Mus musculus LD50 = 87.0 mg/kg ToxVal
- Homo sapiens RfD = 0.002 mg/kg-day ToxVal
- Homo sapiens RfD = 0.0002 mg/kg-day ToxVal
- Homo sapiens RfD (provisional) = 0.002 mg/kg-day ToxVal
- Homo sapiens MEG = 0.028 mg/L ToxVal

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 NPC66775 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
NPC

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC66775 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