Structure

Physi-Chem Properties

Molecular Weight:  356.09
Volume:  325.954
LogP:  0.295
LogD:  1.224
LogS:  -3.159
# Rotatable Bonds:  3
TPSA:  81.08
# H-Bond Aceptor:  6
# H-Bond Donor:  2
# Rings:  3
# Heavy Atoms:  8

MedChem Properties

QED Drug-Likeness Score:  0.742
Synthetic Accessibility Score:  5.302
Fsp3:  0.6
Lipinski Rule-of-5:  Accepted
Pfizer Rule:  Accepted
GSK Rule:  Accepted
BMS Rule:  0
Golden Triangle Rule:  Accepted
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -5.001
MDCK Permeability:  2.0192721422063187e-05
Pgp-inhibitor:  0.009
Pgp-substrate:  0.042
Human Intestinal Absorption (HIA):  0.282
20% Bioavailability (F20%):  0.006
30% Bioavailability (F30%):  0.004

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.786
Plasma Protein Binding (PPB):  81.34710693359375%
Volume Distribution (VD):  0.658
Pgp-substrate:  34.352394104003906%

ADMET: Metabolism

CYP1A2-inhibitor:  0.007
CYP1A2-substrate:  0.106
CYP2C19-inhibitor:  0.157
CYP2C19-substrate:  0.912
CYP2C9-inhibitor:  0.604
CYP2C9-substrate:  0.079
CYP2D6-inhibitor:  0.002
CYP2D6-substrate:  0.067
CYP3A4-inhibitor:  0.087
CYP3A4-substrate:  0.97

ADMET: Excretion

Clearance (CL):  4.132
Half-life (T1/2):  0.901

ADMET: Toxicity

hERG Blockers:  0.007
Human Hepatotoxicity (H-HT):  0.19
Drug-inuced Liver Injury (DILI):  0.965
AMES Toxicity:  0.024
Rat Oral Acute Toxicity:  0.6
Maximum Recommended Daily Dose:  0.736
Skin Sensitization:  0.834
Carcinogencity:  0.846
Eye Corrosion:  0.003
Eye Irritation:  0.008
Respiratory Toxicity:  0.074

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General Info & Identifiers & Properties  
Structure MOL file  
Source Organisms  
Biological Activities  
Similar NPs/Drugs  

  Natural Product: NPC17581

Natural Product ID:  NPC17581
Common Name*:   Bis(Dethio)Bis(Methylthio)Gliotoxin
IUPAC Name:   (3R,5aS,6S,10aR)-6-hydroxy-3-(hydroxymethyl)-2-methyl-3,10a-bis(methylsulfanyl)-6,10-dihydro-5aH-pyrazino[1,2-a]indole-1,4-dione
Synonyms:   3R,10Ar-Dithiomethyl Gliotoxin A
Standard InCHIKey:  OVBAGMZLGLXSBN-UOVKNHIHSA-N
Standard InCHI:  InChI=1S/C15H20N2O4S2/c1-16-12(20)14(22-2)7-9-5-4-6-10(19)11(9)17(14)13(21)15(16,8-18)23-3/h4-6,10-11,18-19H,7-8H2,1-3H3/t10-,11-,14+,15+/m0/s1
SMILES:  CN1C(=O)[C@@]2(CC3=CC=C[C@@H]([C@H]3N2C(=O)[C@@]1(CO)SC)O)SC
Synthetic Gene Cluster:   BGC0000361;
ChEMBL Identifier:   CHEMBL1088981
PubChem CID:   194564
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000264] Organic acids and derivatives
      • [CHEMONTID:0000265] Carboxylic acids and derivatives
        • [CHEMONTID:0000013] Amino acids, peptides, and analogues
          • [CHEMONTID:0000347] Amino acids and derivatives
            • [CHEMONTID:0000060] Alpha amino acids and derivatives

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

  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]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[17616609]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[17929896]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. Berkeley Pit lake n.a. PMID[17970594]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[19113967]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[19159274]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[19256529]
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]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. isolated from sediment collected using a hand held deep water sampling device at >33 m depth in Vanuatu 2003 PMID[20303767]
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]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21667925]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21916432]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21954885]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[22106303]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[22148349]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota stem bark of Melia azedarach n.a. n.a. PMID[22409377]
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]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23557488]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23563483]
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]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[7622436]
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]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO45 Sterculia parviflora Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10070 Scorzonera latifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO677 Parmelia abessinica Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9410 Saussurea macrota 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]
NPO3593 Lagochilus inebrians Species Lamiaceae 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 NP ID 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

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT737 Cell Line HUVEC Homo sapiens IC50 = 1120.0 nM PMID[503822]
NPT470 Individual Protein Rhodesain Trypanosoma brucei rhodesiense IC50 > 50000.0 nM PMID[503822]
NPT15 Cell Line Jurkat Homo sapiens IC50 = 140000.0 nM PMID[503822]
NPT165 Cell Line HeLa Homo sapiens IC50 > 2810.0 nM PMID[503822]
NPT1384 Individual Protein Farnesyl diphosphate synthase Homo sapiens IC50 > 100000.0 nM PMID[503822]
NPT90 Cell Line DU-145 Homo sapiens Inhibition = 22.0 % PMID[503823]
NPT168 Cell Line P388 Mus musculus IC50 = 110.0 nM PMID[503824]
NPT5 Individual Protein Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Homo sapiens IC50 > 100000.0 nM PMID[503824]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei IC50 = 40200.0 nM PMID[503822]
NPT2 Others Unspecified IC50 > 50000.0 nM PMID[503822]
NPT2 Others Unspecified Ratio IC50 = 3.5 n.a. PMID[503822]
NPT2 Others Unspecified IC50 = 8400.0 nM PMID[503822]
NPT32 Organism Mus musculus Mus musculus LD50 > 500.0 mg.kg-1 PMID[503822]
NPT2 Others Unspecified ED50 > 10.0 uM PMID[503822]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

  Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

●  The left chart: Distribution of similarity level between NPC17581 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.56 or Top200).

Similarity Score Similarity Level Natural Product ID
1.0 High Similarity NPC476155
0.9189 High Similarity NPC272166
0.9115 High Similarity NPC470300
0.9107 High Similarity NPC66007
0.8974 High Similarity NPC97580
0.887 High Similarity NPC470788
0.7874 Intermediate Similarity NPC41162
0.766 Intermediate Similarity NPC475342
0.7231 Intermediate Similarity NPC262880
0.7231 Intermediate Similarity NPC247902
0.6972 Remote Similarity NPC471680
0.6783 Remote Similarity NPC276822
0.675 Remote Similarity NPC188785
0.6691 Remote Similarity NPC82129
0.6667 Remote Similarity NPC469455
0.6614 Remote Similarity NPC314550
0.6607 Remote Similarity NPC475975
0.6418 Remote Similarity NPC302169
0.6412 Remote Similarity NPC28542
0.6403 Remote Similarity NPC120335
0.6371 Remote Similarity NPC476877
0.6324 Remote Similarity NPC36254
0.627 Remote Similarity NPC476876
0.6259 Remote Similarity NPC8325
0.6228 Remote Similarity NPC302235
0.6222 Remote Similarity NPC315188
0.6198 Remote Similarity NPC469739
0.6154 Remote Similarity NPC324506
0.6116 Remote Similarity NPC313265
0.609 Remote Similarity NPC288629
0.6087 Remote Similarity NPC211848
0.6053 Remote Similarity NPC277341
0.6053 Remote Similarity NPC226982
0.6043 Remote Similarity NPC309525
0.6031 Remote Similarity NPC476875
0.6031 Remote Similarity NPC59249
0.6015 Remote Similarity NPC474984
0.5985 Remote Similarity NPC474995
0.5954 Remote Similarity NPC251122
0.5923 Remote Similarity NPC207820
0.5878 Remote Similarity NPC25025
0.5873 Remote Similarity NPC474985
0.5852 Remote Similarity NPC271115
0.5846 Remote Similarity NPC271562
0.5845 Remote Similarity NPC220396
0.5833 Remote Similarity NPC469666
0.5827 Remote Similarity NPC77703
0.5821 Remote Similarity NPC309731
0.5816 Remote Similarity NPC175726
0.5816 Remote Similarity NPC474082
0.5814 Remote Similarity NPC133420
0.5802 Remote Similarity NPC474099
0.5781 Remote Similarity NPC473289
0.5775 Remote Similarity NPC476951
0.5766 Remote Similarity NPC471673
0.5765 Remote Similarity NPC166169
0.5762 Remote Similarity NPC309450
0.5762 Remote Similarity NPC475266
0.5762 Remote Similarity NPC304299
0.5762 Remote Similarity NPC247776
0.5762 Remote Similarity NPC475278
0.5739 Remote Similarity NPC471768
0.5733 Remote Similarity NPC315210
0.5733 Remote Similarity NPC315848
0.5714 Remote Similarity NPC273185
0.5705 Remote Similarity NPC283783
0.5695 Remote Similarity NPC469800
0.5694 Remote Similarity NPC25327
0.569 Remote Similarity NPC209232
0.5682 Remote Similarity NPC476276
0.5671 Remote Similarity NPC328270
0.5659 Remote Similarity NPC471097
0.5659 Remote Similarity NPC475149
0.5658 Remote Similarity NPC71866
0.5649 Remote Similarity NPC243412
0.5643 Remote Similarity NPC160688
0.5643 Remote Similarity NPC266910
0.5638 Remote Similarity NPC248283
0.5625 Remote Similarity NPC475791
0.5625 Remote Similarity NPC13175
0.5621 Remote Similarity NPC470301
0.5613 Remote Similarity NPC314358
0.56 Remote Similarity NPC9687
0.56 Remote Similarity NPC474811
0.56 Remote Similarity NPC151706
0.56 Remote Similarity NPC475318
0.56 Remote Similarity NPC79465
0.56 Remote Similarity NPC118099
0.56 Remote Similarity NPC474855
0.56 Remote Similarity NPC476102
0.56 Remote Similarity NPC76785
0.56 Remote Similarity NPC260045
0.56 Remote Similarity NPC293377
0.56 Remote Similarity NPC90194
0.56 Remote Similarity NPC474787
0.56 Remote Similarity NPC273907
0.56 Remote Similarity NPC49577
0.56 Remote Similarity NPC475598

  Chemically structural similarity: II. Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC17581 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.9189 High Similarity NPD1000 Clinical (unspecified phase)
0.6269 Remote Similarity NPD2645 Approved
0.622 Remote Similarity NPD2147 Approved
0.6194 Remote Similarity NPD3159 Discontinued
0.6176 Remote Similarity NPD1806 Approved
0.6 Remote Similarity NPD1773 Discontinued
0.6 Remote Similarity NPD2099 Approved
0.5985 Remote Similarity NPD2090 Approved
0.596 Remote Similarity NPD5264 Approved
0.596 Remote Similarity NPD5265 Approved
0.5946 Remote Similarity NPD4126 Approved
0.5929 Remote Similarity NPD3677 Clinical (unspecified phase)
0.5827 Remote Similarity NPD1748 Approved
0.5816 Remote Similarity NPD8273 Phase 1
0.5769 Remote Similarity NPD777 Phase 3
0.5769 Remote Similarity NPD7333 Discontinued
0.5725 Remote Similarity NPD1713 Approved
0.5704 Remote Similarity NPD1376 Discontinued
0.5704 Remote Similarity NPD2148 Clinical (unspecified phase)
0.5694 Remote Similarity NPD2585 Clinical (unspecified phase)
0.5685 Remote Similarity NPD5263 Approved
0.5685 Remote Similarity NPD4125 Approved
0.5683 Remote Similarity NPD806 Approved
0.5683 Remote Similarity NPD805 Approved
0.5676 Remote Similarity NPD3561 Clinical (unspecified phase)
0.5667 Remote Similarity NPD8172 Phase 2
0.5667 Remote Similarity NPD5004 Approved
0.5667 Remote Similarity NPD6073 Approved
0.5667 Remote Similarity NPD8173 Phase 2
0.5634 Remote Similarity NPD4706 Clinical (unspecified phase)
0.5616 Remote Similarity NPD4175 Approved
0.5616 Remote Similarity NPD4177 Approved
0.56 Remote Similarity NPD5767 Discontinued
0.56 Remote Similarity NPD7113 Clinical (unspecified phase)

  Bioactivity similarity: Similar Natural Products in NPASS

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