Structure

Physi-Chem Properties

Molecular Weight:  356.09
Volume:  325.954
LogP:  0.369
LogD:  1.277
LogS:  -3.381
# 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:  0.734
Synthetic Accessibility Score:  5.357
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:  -5.006
MDCK Permeability:  1.9000028260052204e-05
Pgp-inhibitor:  0.264
Pgp-substrate:  0.225
Human Intestinal Absorption (HIA):  0.851
20% Bioavailability (F20%):  0.031
30% Bioavailability (F30%):  0.02

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.898
Plasma Protein Binding (PPB):  71.69755554199219%
Volume Distribution (VD):  0.698
Pgp-substrate:  40.21788024902344%

ADMET: Metabolism

CYP1A2-inhibitor:  0.014
CYP1A2-substrate:  0.105
CYP2C19-inhibitor:  0.081
CYP2C19-substrate:  0.901
CYP2C9-inhibitor:  0.542
CYP2C9-substrate:  0.073
CYP2D6-inhibitor:  0.001
CYP2D6-substrate:  0.06
CYP3A4-inhibitor:  0.023
CYP3A4-substrate:  0.965

ADMET: Excretion

Clearance (CL):  4.497
Half-life (T1/2):  0.907

ADMET: Toxicity

hERG Blockers:  0.024
Human Hepatotoxicity (H-HT):  0.172
Drug-inuced Liver Injury (DILI):  0.82
AMES Toxicity:  0.061
Rat Oral Acute Toxicity:  0.952
Maximum Recommended Daily Dose:  0.71
Skin Sensitization:  0.904
Carcinogencity:  0.855
Eye Corrosion:  0.003
Eye Irritation:  0.01
Respiratory Toxicity:  0.07

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

  Natural Product: NPC470788

Natural Product ID:  NPC470788
Common Name*:   Bisdethiobis(Methylthio)Gliotoxin
IUPAC Name:   (3R,6aR,7S,10bR)-7-hydroxy-3-(hydroxymethyl)-2-methyl-3,10b-bis(methylsulfanyl)-6a,7-dihydro-6H-pyrazino[2,1-a]isoindole-1,4-dione
Synonyms:  
Standard InCHIKey:  DPYAQFVXNBCLEG-YZENIEGJSA-N
Standard InCHI:  InChI=1S/C15H20N2O4S2/c1-16-13(21)15(23-3)10-5-4-6-11(19)9(10)7-17(15)12(20)14(16,8-18)22-2/h4-6,9,11,18-19H,7-8H2,1-3H3/t9-,11-,14+,15+/m0/s1
SMILES:  CN1C(=O)C2(C3=CC=CC(C3CN2C(=O)C1(CO)SC)O)SC
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL2229126
PubChem CID:   76325969
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
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]
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]
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]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21667925]
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]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota stem bark of Melia azedarach n.a. n.a. PMID[22409377]
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]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[7622436]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10538 Aspergillus fumigatus Species Aspergillaceae 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
NPT176 Organism Artemia salina Artemia salina LC50 = 33.5 ug.mL-1 PMID[448440]

☑ 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 NPC470788 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
0.887 High Similarity NPC17581
0.887 High Similarity NPC476155
0.8136 Intermediate Similarity NPC272166
0.8083 Intermediate Similarity NPC470300
0.8067 Intermediate Similarity NPC66007
0.7984 Intermediate Similarity NPC97580
0.7538 Intermediate Similarity NPC41162
0.7483 Intermediate Similarity NPC475342
0.696 Remote Similarity NPC314550
0.6917 Remote Similarity NPC262880
0.6917 Remote Similarity NPC247902
0.6833 Remote Similarity NPC188785
0.6736 Remote Similarity NPC276822
0.669 Remote Similarity NPC471680
0.6493 Remote Similarity NPC302169
0.6404 Remote Similarity NPC475975
0.6357 Remote Similarity NPC59249
0.6357 Remote Similarity NPC120335
0.632 Remote Similarity NPC476877
0.6296 Remote Similarity NPC315188
0.6281 Remote Similarity NPC469739
0.622 Remote Similarity NPC476876
0.6214 Remote Similarity NPC8325
0.6159 Remote Similarity NPC36254
0.6154 Remote Similarity NPC251122
0.6119 Remote Similarity NPC28542
0.6107 Remote Similarity NPC469455
0.6102 Remote Similarity NPC324506
0.609 Remote Similarity NPC474984
0.6069 Remote Similarity NPC82129
0.6066 Remote Similarity NPC313265
0.6061 Remote Similarity NPC474995
0.6016 Remote Similarity NPC40663
0.6014 Remote Similarity NPC315848
0.6014 Remote Similarity NPC315210
0.6 Remote Similarity NPC277341
0.6 Remote Similarity NPC226982
0.6 Remote Similarity NPC302235
0.6 Remote Similarity NPC309525
0.5985 Remote Similarity NPC476875
0.5957 Remote Similarity NPC476951
0.5952 Remote Similarity NPC474985
0.5926 Remote Similarity NPC288629
0.5926 Remote Similarity NPC271115
0.5923 Remote Similarity NPC271562
0.5906 Remote Similarity NPC77703
0.5897 Remote Similarity NPC314050
0.5897 Remote Similarity NPC315809
0.5891 Remote Similarity NPC133420
0.5878 Remote Similarity NPC474099
0.5878 Remote Similarity NPC207820
0.5859 Remote Similarity NPC471097
0.5859 Remote Similarity NPC475149
0.5846 Remote Similarity NPC471259
0.5816 Remote Similarity NPC211848
0.5793 Remote Similarity NPC469666
0.5781 Remote Similarity NPC100810
0.5781 Remote Similarity NPC144714
0.5775 Remote Similarity NPC474082
0.5775 Remote Similarity NPC175726
0.5772 Remote Similarity NPC90194
0.5772 Remote Similarity NPC79465
0.5772 Remote Similarity NPC293377
0.5772 Remote Similarity NPC260045
0.5772 Remote Similarity NPC475318
0.5772 Remote Similarity NPC118099
0.5772 Remote Similarity NPC9687
0.5772 Remote Similarity NPC474787
0.5772 Remote Similarity NPC476102
0.5772 Remote Similarity NPC273907
0.5772 Remote Similarity NPC49577
0.5772 Remote Similarity NPC475598
0.5772 Remote Similarity NPC76785
0.5772 Remote Similarity NPC151706
0.5772 Remote Similarity NPC474855
0.5772 Remote Similarity NPC474811
0.5769 Remote Similarity NPC283783
0.5764 Remote Similarity NPC470539
0.5758 Remote Similarity NPC476276
0.5755 Remote Similarity NPC477140
0.5755 Remote Similarity NPC477143
0.5736 Remote Similarity NPC474244
0.5736 Remote Similarity NPC473289
0.5735 Remote Similarity NPC50694
0.5725 Remote Similarity NPC476952
0.5714 Remote Similarity NPC160688
0.5703 Remote Similarity NPC475791
0.5703 Remote Similarity NPC13175
0.5695 Remote Similarity NPC89489
0.5693 Remote Similarity NPC296043
0.5692 Remote Similarity NPC279833
0.5692 Remote Similarity NPC80439
0.5692 Remote Similarity NPC471260
0.5692 Remote Similarity NPC173690
0.5682 Remote Similarity NPC176773
0.5677 Remote Similarity NPC314358
0.5676 Remote Similarity NPC99864
0.5674 Remote Similarity NPC273185
0.5672 Remote Similarity NPC473232
0.566 Remote Similarity NPC473341
0.5658 Remote Similarity NPC469800
0.5658 Remote Similarity NPC239762
0.5658 Remote Similarity NPC163392
0.5655 Remote Similarity NPC25327
0.5652 Remote Similarity NPC329216
0.5652 Remote Similarity NPC201968
0.5649 Remote Similarity NPC64168
0.5646 Remote Similarity NPC300315
0.5638 Remote Similarity NPC287401
0.5636 Remote Similarity NPC328270
0.5625 Remote Similarity NPC475758
0.5621 Remote Similarity NPC304299
0.5621 Remote Similarity NPC309450
0.5621 Remote Similarity NPC247776
0.5621 Remote Similarity NPC475266
0.5621 Remote Similarity NPC475278
0.562 Remote Similarity NPC103391
0.562 Remote Similarity NPC472536
0.5615 Remote Similarity NPC471258
0.5613 Remote Similarity NPC243412
0.5613 Remote Similarity NPC316008
0.5613 Remote Similarity NPC313867
0.5612 Remote Similarity NPC471673
0.5612 Remote Similarity NPC201889
0.5612 Remote Similarity NPC106791
0.5608 Remote Similarity NPC120420
0.5606 Remote Similarity NPC476328
0.5606 Remote Similarity NPC472856

  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 NPC470788 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
0.8136 Intermediate Similarity NPD1000 Clinical (unspecified phase)
0.6591 Remote Similarity NPD2645 Approved
0.6493 Remote Similarity NPD1806 Approved
0.6391 Remote Similarity NPD3159 Discontinued
0.6316 Remote Similarity NPD1773 Discontinued
0.6232 Remote Similarity NPD3677 Clinical (unspecified phase)
0.6172 Remote Similarity NPD2147 Approved
0.6131 Remote Similarity NPD1748 Approved
0.6 Remote Similarity NPD2148 Clinical (unspecified phase)
0.5985 Remote Similarity NPD805 Approved
0.5985 Remote Similarity NPD806 Approved
0.5969 Remote Similarity NPD777 Phase 3
0.5878 Remote Similarity NPD5767 Discontinued
0.5846 Remote Similarity NPD7333 Discontinued
0.5839 Remote Similarity NPD2099 Approved
0.5821 Remote Similarity NPD2090 Approved
0.5817 Remote Similarity NPD5265 Approved
0.5817 Remote Similarity NPD5264 Approved
0.58 Remote Similarity NPD4126 Approved
0.5778 Remote Similarity NPD1376 Discontinued
0.5775 Remote Similarity NPD8273 Phase 1
0.5733 Remote Similarity NPD5004 Approved
0.5733 Remote Similarity NPD8173 Phase 2
0.5733 Remote Similarity NPD8172 Phase 2
0.5724 Remote Similarity NPD7751 Phase 1
0.5683 Remote Similarity NPD1713 Approved
0.5676 Remote Similarity NPD8415 Approved
0.5655 Remote Similarity NPD2585 Clinical (unspecified phase)
0.5646 Remote Similarity NPD4125 Approved
0.5638 Remote Similarity NPD8387 Clinical (unspecified phase)
0.5638 Remote Similarity NPD3561 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