Natural Product: NPC272166

Natural Product IDNPC272166
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Gliotoxin
IUPAC Name n.a.
Synonyms Gliotoxin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL331627
PubChem CID 6223
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0002389] Diazinanes
        • [CHEMONTID:0000189] Piperazines
          • [CHEMONTID:0001731] Dioxopiperazines
            • [CHEMONTID:0003684] 2,5-dioxopiperazines
              • [CHEMONTID:0001732] Thiodioxopiperazines
                • [CHEMONTID:0001790] Epipolythiodioxopiperazines
                  • [CHEMONTID:0001791] Gliotoxins

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 FIVPIPIDMRVLAY-RBJBARPLSA-N
Standard InCHI InChI=1S/C13H14N2O4S2/c1-14-10(18)12-5-7-3-2-4-8(17)9(7)15(12)11(19)13(14,6-16)21-20-12/h2-4,8-9,16-17H,5-6H2,1H3/t8-,9-,12+,13+/m0/s1
SMILES CN1C(=O)[C@]23CC4=CC=C[C@@H]([C@H]4N2C(=O)[C@@]1(CO)SS3)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   326.04 Volume:   282.805
?
Van der Waals volume.
Dense:   1.153 LogP:   0.383
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.921
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.479
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   20.0
TPSA:   81.08
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.644 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.215 Fsp3:   0.538
MCE-18:   87.5
?
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:   0.178 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.044
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.086
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.865 Promiscuous compounds:   0.262

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.513 MDCK Permeability:   -5.008
Pgp-inhibitor:   0.103 Pgp-substrate:   0.64
PAMPA:   0.97
?
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):   0.747
20% Bioavailability (F20%):   0.39 30% Bioavailability (F30%):   0.968
50% Bioavailability (F50%):   0.967

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.011 MRP1:   0.769
Plasma Protein Binding (PPB):   52.287% Volume Distribution (VD):   -0.216
Fu: 52.067%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.578
OATP1B3 inhibitor:   0.88 BCRP inhibitor:   0.042
BSEP inhibitor:   0.576

ADMET: Metabolism

CYP1A2-inhibitor:   0.988 CYP1A2-substrate:   0.636
CYP2C19-inhibitor:   0.965 CYP2C19-substrate:   0.023
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.023 CYP2D6-substrate:   0.003
CYP3A4-inhibitor:   0.987 CYP3A4-substrate:   0.994
CYP2B6-substrate:   0.191 CYP2C8-inhibitor:   0.081
HLM stability:   0.292
?
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):  5.371 Half-life (T1/2):  1.045

ADMET: Toxicity

hERG Blockers:  0.202 hERG Blockers (10um):  0.121
Human Hepatotoxicity (H-HT):  0.165 Drug-induced Liver Injury (DILI):  0.999
AMES Toxicity:  0.197 Rat Oral Acute Toxicity:  0.791
Maximum Recommended Daily Dose:  0.282 Skin Sensitization:  1.0
Carcinogencity:  0.049 Eye Corrosion:  0.0
Eye Irritation:  0.322 Respiratory Toxicity:  0.917
Drug-induced Neurotoxicity:  0.121 Ototoxicity:  0.006
Hematotoxicity:  0.657 Drug-induced Nephrotoxicity:  0.927
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.755
A549 Cytotoxicity:  0.002 Hek293 Cytotoxicity:  0.3
BCF:   0.519
?
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:   3.232
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.918
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.102
?
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
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[10479323]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[12350167]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[14640527]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota Axinella verrucosa Mediterranean n.a. PMID[14738391]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[15043411]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. Sussex Inlet, New South Wales, Australia n.a. PMID[15104517]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[15332862]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. Berkeley Pit lake n.a. PMID[17970594]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. New Zealand n.a. PMID[19323568]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[19326880]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[20452770]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. North Sea n.a. PMID[21126094]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21126094]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. Limonium tubiflorum n.a. PMID[21146414]
NPO40883 Metulocladosporiella sp. Species n.a. n.a. n.a. n.a. n.a. PMID[21761939]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21916432]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[22148349]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[22458669]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23360521]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23477451]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23603293]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23972215]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[24033077]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[24437979]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[31433188]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[9392888]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO45 Sterculia parviflora Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4038 Phelline comosa Species Phellinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1256 Boronia ledifolia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3593 Lagochilus inebrians Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO40883 Metulocladosporiella sp. Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO10070 Scorzonera latifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12137 Elysia tuca Species Placobranchidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9410 Saussurea macrota Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1256 Boronia ledifolia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO677 Parmelia abessinica Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO45 Sterculia parviflora Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3593 Lagochilus inebrians Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4038 Phelline comosa Species Phellinaceae 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
NPT198 Individual protein Vitamin D receptor Homo sapiens Potency n.a. 3981.1 nM PubChem BioAssay data set
NPT470 Individual protein Rhodesain Trypanosoma brucei rhodesiense IC50 > 50000.0 nM PMID[20303767]
NPT55 Individual protein Putative fructose-1,6-bisphosphate aldolase Giardia intestinalis Potency = 22334.2 nM PubChem BioAssay data set
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 44.7 nM PubChem BioAssay data set
NPT1181 Protein complex Geranylgeranyl transferase type I Homo sapiens IC50 = 17000.0 nM PMID[14552752]
NPT67 Individual protein Cholinesterase Equus caballus Inhibition = 10.3 % PMID[23062825]
NPT5109 Individual protein Creatine kinase M Homo sapiens Activity = 32.0 % DOI[10.1016/S0960-894X(97)10052-X]
NPT5634 Individual protein Mycothiol S-conjugate amidase Mycobacterium tuberculosis IC50 = 50000.0 nM PMID[20303767]
NPT66 Individual protein Acetylcholinesterase Electrophorus electricus Inhibition = -11.27 % PMID[23062825]
NPT1180 Protein complex Protein farnesyltransferase Homo sapiens IC50 = 1100.0 nM PMID[9301658]
NPT1180 Protein complex Protein farnesyltransferase Homo sapiens IC50 = 80000.0 nM PMID[14552752]
NPT5633 Individual protein Acetolactate synthase catalytic subunit, mitochondrial Saccharomyces cerevisiae S288c IC50 = 200.0 nM PMID[20303767]
NPT53 Individual protein 4'-phosphopantetheinyl transferase ffp Bacillus subtilis Potency = 2511.9 nM PubChem BioAssay data set
NPT5 Individual protein Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Homo sapiens IC50 = 6400.0 nM PMID[22148349]
NPT5635 Individual protein Histone-lysine N-methyltransferase SUV39H1 Homo sapiens IC50 = 260.0 nM PMID[22975593]
NPT5 Individual protein Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Homo sapiens IC50 = 530.0 nM PMID[22975593]
NPT52 Individual protein Pyruvate kinase isozymes M1/M2 Homo sapiens IC50 = 22640.0 nM PMID[34726055]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT4849 Cell line P815 Mus musculus ED50 = 2.0 uM DOI[10.1016/S0960-894X(97)10052-X]
NPT404 Cell line CCRF-CEM Homo sapiens IC50 = 150.0 nM PMID[16124785]
NPT165 Cell line HeLa Homo sapiens IC50 = 2450.0 nM PMID[20303767]
NPT15 Cell line Jurkat Homo sapiens IC50 < 1000.0 nM PMID[20303767]
NPT81 Cell line A549 Homo sapiens IC50 = 3.0 nM PMID[20303767]
NPT737 Cell line HUVEC Homo sapiens IC50 = 123.0 nM PMID[20303767]
NPT168 Cell line P388 Mus musculus IC50 = 24.0 nM PMID[22148349]
NPT561 Organism Tetrahymena pyriformis Tetrahymena pyriformis EC50 = 380.0 nM PMID[20303767]
NPT722 Organism Athelia rolfsii Athelia rolfsii ED50 = 6.47 uM PMID[20303767]
NPT529 Organism Rhizoctonia solani Rhizoctonia solani ED50 = 9.75 uM PMID[20303767]
NPT20 Organism Candida albicans Candida albicans IC50 = 3100.0 nM PMID[16124785]
NPT2703 Organism Rhizoctonia bataticola Rhizoctonia bataticola ED50 = 0.9 uM PMID[20303767]
NPT2701 Organism Pythium debaryanum Pythium debaryanum ED50 = 90.12 uM PMID[20303767]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae MIC = 0.5 ug.mL-1 PMID[18212113]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae MIC = 8.0 ug.mL-1 PMID[18212113]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae MIC = 2.0 ug.mL-1 PMID[18212113]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae MIC = 16.0 ug.mL-1 PMID[18212113]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae MIC = 0.06 ug.mL-1 PMID[18212113]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae MIC = 0.125 ug.mL-1 PMID[18212113]
NPT20 Organism Candida albicans Candida albicans MIC = 4.0 ug.mL-1 PMID[21761939]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC < 30.0 nM PMID[30685527]
NPT4304 Organism Macrophomina phaseolina Macrophomina phaseolina ED50 = 5.4 uM PMID[20303767]
NPT961 Organism Pythium aphanidermatum Pythium aphanidermatum ED50 = 36.87 uM PMID[20303767]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei IC50 = 10.0 nM PMID[20303767]
NPT2 Others Unspecified n.a. IC50 = 500.0 nM PMID[20303767]
NPT2 Others Unspecified n.a. IC50 = 93000.0 nM PMID[20303767]
NPT2 Others Unspecified n.a. Activity = 300.0 nM PMID[20303767]
NPT2 Others Unspecified n.a. IC50 = 10000.0 nM PMID[20303767]
NPT485 Organism Plasmodium falciparum (isolate K1 / Thailand) Plasmodium falciparum K1 IC50 = 3600.0 nM PMID[20303767]
NPT2 Others Unspecified n.a. ED50 = 0.104 uM PMID[20303767]
NPT2 Others Unspecified n.a. Activity = 30.7 uM PMID[20303767]
NPT2 Others Unspecified n.a. Activity = 0.3 uM PMID[20303767]
NPT2 Others Unspecified n.a. IC50 = 9000.0 nM PMID[20303767]
NPT2 Others Unspecified n.a. Potency n.a. 2511.9 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 1412.5 nM PubChem BioAssay data set
NPT26787 Protein complex Sharpin/RBCK1/RNF31 Homo sapiens IC50 = 510.0 nM PMID[28505447]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus ED50 = 0.35 uM DOI[10.1016/S0960-894X(97)10052-X]
NPT32 Organism Mus musculus Mus musculus Activity = 59.0 % DOI[10.1016/S0960-894X(97)10052-X]





 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
- Mus musculus LD50 = 17.9 mg.kg-1 PMID[20303767]

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 NPC272166 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
0.75 Intermediate Similarity NPC66007
0.6071 Remote Similarity NPC610725
0.5536 Remote Similarity NPC476155
0.5536 Remote Similarity NPC17581

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC272166 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
1.0 High Similarity NPD1000 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