Natural Product: NPC200214

Natural Product IDNPC200214
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Glypetelotine
IUPAC Name S-methyl N-[2-(1H-indol-3-yl)ethyl]-N-methylcarbamothioate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3314412
PubChem CID 403138
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 ASGGNXXOFLVYSB-UHFFFAOYSA-N
Standard InCHI InChI=1S/C13H16N2OS/c1-15(13(16)17-2)8-7-10-9-14-12-6-4-3-5-11(10)12/h3-6,9,14H,7-8H2,1-2H3
SMILES CN(CCc1c[nH]c2ccccc12)C(=O)SC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   248.1 Volume:   252.402
?
Van der Waals volume.
Dense:   0.983 LogP:   2.856
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.997
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.48
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   11.0
TPSA:   36.1
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.906 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.4 Fsp3:   0.308
MCE-18:   11.0
?
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:   0.028 Fluc inhibitor:   0.008
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.147
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.304
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.133 Promiscuous compounds:   0.37

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.416 MDCK Permeability:   -4.707
Pgp-inhibitor:   0.734 Pgp-substrate:   0.058
PAMPA:   0.108
?
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):   0.046
20% Bioavailability (F20%):   0.112 30% Bioavailability (F30%):   0.325
50% Bioavailability (F50%):   0.72

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.932 MRP1:   0.721
Plasma Protein Binding (PPB):   96.836% Volume Distribution (VD):   0.341
Fu: 2.576%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.714
OATP1B3 inhibitor:   0.799 BCRP inhibitor:   0.309
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.984
CYP2C19-inhibitor:   0.984 CYP2C19-substrate:   0.807
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   0.219
CYP2D6-inhibitor:   0.997 CYP2D6-substrate:   0.053
CYP3A4-inhibitor:   0.995 CYP3A4-substrate:   0.899
CYP2B6-substrate:   0.994 CYP2C8-inhibitor:   0.981
HLM stability:   0.921
?
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):  7.418 Half-life (T1/2):  0.579

ADMET: Toxicity

hERG Blockers:  0.231 hERG Blockers (10um):  0.51
Human Hepatotoxicity (H-HT):  0.502 Drug-induced Liver Injury (DILI):  0.843
AMES Toxicity:  0.564 Rat Oral Acute Toxicity:  0.657
Maximum Recommended Daily Dose:  0.499 Skin Sensitization:  0.944
Carcinogencity:  0.532 Eye Corrosion:  0.007
Eye Irritation:  0.74 Respiratory Toxicity:  0.88
Drug-induced Neurotoxicity:  0.814 Ototoxicity:  0.271
Hematotoxicity:  0.41 Drug-induced Nephrotoxicity:  0.498
Genotoxicity:  0.91 RPMI-8226 Immunitoxicity:  0.052
A549 Cytotoxicity:  0.154 Hek293 Cytotoxicity:  0.315
BCF:   1.1
?
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:   3.566
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.298
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.529
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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
NPO13162 Glycosmis petelotii Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[24949913]
NPO13162 Glycosmis petelotii Species Rutaceae 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
NPT2685 Protein family Voltage-gated L-type calcium channel Rattus norvegicus IC50 = 15848.93 nM PMID[19403314]
NPT2685 Protein family Voltage-gated L-type calcium channel Rattus norvegicus Emax = 99.0 % PMID[24949913]
NPT2685 Protein family Voltage-gated L-type calcium channel Rattus norvegicus IC50 = 31622.78 nM PMID[9873730]
NPT2685 Protein family Voltage-gated L-type calcium channel Rattus norvegicus Emax = 95.6 % PMID[24949913]
NPT2685 Protein family Voltage-gated L-type calcium channel Rattus norvegicus IC50 = 19952.62 nM PMID[12361396]
NPT2685 Protein family Voltage-gated L-type calcium channel Rattus norvegicus Emax = 94.8 % PMID[24949913]
NPT2685 Protein family Voltage-gated L-type calcium channel Rattus norvegicus IC50 = 39810.72 nM PMID[19770287]
NPT2685 Protein family Voltage-gated L-type calcium channel Rattus norvegicus Emax = 85.2 % PMID[24949913]
NPT2685 Protein family Voltage-gated L-type calcium channel Rattus norvegicus Inhibition = 100.0 % PMID[20704304]
NPT2685 Protein family Voltage-gated L-type calcium channel Rattus norvegicus Inhibition = 74.0 % PMID[15387655]
NPT2685 Protein family Voltage-gated L-type calcium channel Rattus norvegicus IC50 = 251000.0 nM PMID[9934464]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC200214 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
0.7143 Intermediate Similarity NPC600736
0.6531 Remote Similarity NPC310665
0.6038 Remote Similarity NPC605329
0.5636 Remote Similarity NPC480551
0.5614 Remote Similarity NPC480550
0.5614 Remote Similarity NPC480549
0.5593 Remote Similarity NPC480548
0.5532 Remote Similarity NPC601214
0.5439 Remote Similarity NPC469358
0.54 Remote Similarity NPC138370
0.54 Remote Similarity NPC279081
0.5357 Remote Similarity NPC489200
0.5323 Remote Similarity NPC474561
0.5294 Remote Similarity NPC29886
0.5254 Remote Similarity NPC602670
0.52 Remote Similarity NPC96102
0.5172 Remote Similarity NPC608269
0.5098 Remote Similarity NPC230869
0.5091 Remote Similarity NPC78020

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC200214 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
0.5714 Remote Similarity NPD1722 Phase 4
0.5283 Remote Similarity NPD786 Pre-clinical
0.52 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