Structure

Physi-Chem Properties

Molecular Weight:  168.09
Volume:  164.112
LogP:  -0.535
LogD:  -0.703
LogS:  -0.767
# Rotatable Bonds:  0
TPSA:  49.41
# H-Bond Aceptor:  4
# H-Bond Donor:  1
# Rings:  2
# Heavy Atoms:  4

MedChem Properties

QED Drug-Likeness Score:  0.53
Synthetic Accessibility Score:  3.075
Fsp3:  0.75
Lipinski Rule-of-5:  Accepted
Pfizer Rule:  Accepted
GSK Rule:  Accepted
BMS Rule:  0
Golden Triangle Rule:  Rejected
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -4.969
MDCK Permeability:  2.4940762159531005e-05
Pgp-inhibitor:  0.002
Pgp-substrate:  0.018
Human Intestinal Absorption (HIA):  0.033
20% Bioavailability (F20%):  0.01
30% Bioavailability (F30%):  0.021

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.902
Plasma Protein Binding (PPB):  9.529729843139648%
Volume Distribution (VD):  0.714
Pgp-substrate:  81.74097442626953%

ADMET: Metabolism

CYP1A2-inhibitor:  0.011
CYP1A2-substrate:  0.122
CYP2C19-inhibitor:  0.032
CYP2C19-substrate:  0.308
CYP2C9-inhibitor:  0.014
CYP2C9-substrate:  0.339
CYP2D6-inhibitor:  0.007
CYP2D6-substrate:  0.23
CYP3A4-inhibitor:  0.009
CYP3A4-substrate:  0.117

ADMET: Excretion

Clearance (CL):  5.214
Half-life (T1/2):  0.733

ADMET: Toxicity

hERG Blockers:  0.005
Human Hepatotoxicity (H-HT):  0.678
Drug-inuced Liver Injury (DILI):  0.114
AMES Toxicity:  0.01
Rat Oral Acute Toxicity:  0.054
Maximum Recommended Daily Dose:  0.061
Skin Sensitization:  0.181
Carcinogencity:  0.014
Eye Corrosion:  0.004
Eye Irritation:  0.041
Respiratory Toxicity:  0.053

Download Data

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

  Natural Product: NPC128005

Natural Product ID:  NPC128005
Common Name*:   (3S,8Ar)-3-Methylhexahydropyrrolo[1,2-A]Pyrazine-1,4-Dione
IUPAC Name:   (3S,8aR)-3-methyl-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
Synonyms:  
Standard InCHIKey:  WSLYCILIEOFQPK-NTSWFWBYSA-N
Standard InCHI:  InChI=1S/C8H12N2O2/c1-5-8(12)10-4-2-3-6(10)7(11)9-5/h5-6H,2-4H2,1H3,(H,9,11)/t5-,6+/m0/s1
SMILES:  OC1=N[C@@H](C)C(=O)N2[C@@H]1CCC2
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL2229106
PubChem CID:   5325711
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 > 100.0 ug.mL-1 PMID[497132]

☑ 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 NPC128005 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 NPC84182
0.95 High Similarity NPC243964
0.9231 High Similarity NPC196007
0.9231 High Similarity NPC76297
0.9231 High Similarity NPC214532
0.8955 High Similarity NPC126186
0.8955 High Similarity NPC161774
0.8955 High Similarity NPC256312
0.8955 High Similarity NPC266888
0.8955 High Similarity NPC209156
0.8939 High Similarity NPC470781
0.8429 Intermediate Similarity NPC470782
0.8333 Intermediate Similarity NPC312315
0.8108 Intermediate Similarity NPC470783
0.76 Intermediate Similarity NPC31756
0.7568 Intermediate Similarity NPC59867
0.75 Intermediate Similarity NPC476117
0.75 Intermediate Similarity NPC476156
0.75 Intermediate Similarity NPC476243
0.75 Intermediate Similarity NPC476137
0.7403 Intermediate Similarity NPC476302
0.7324 Intermediate Similarity NPC322274
0.7179 Intermediate Similarity NPC475542
0.7143 Intermediate Similarity NPC287693
0.6951 Remote Similarity NPC477539
0.6842 Remote Similarity NPC327272
0.6711 Remote Similarity NPC320221
0.6628 Remote Similarity NPC475801
0.6628 Remote Similarity NPC474593
0.6552 Remote Similarity NPC474576
0.6552 Remote Similarity NPC477538
0.6512 Remote Similarity NPC275715
0.6477 Remote Similarity NPC471098
0.6477 Remote Similarity NPC173763
0.6477 Remote Similarity NPC62263
0.6463 Remote Similarity NPC184473
0.6389 Remote Similarity NPC57420
0.6364 Remote Similarity NPC29326
0.6338 Remote Similarity NPC314510
0.6265 Remote Similarity NPC84128
0.6265 Remote Similarity NPC53858
0.625 Remote Similarity NPC329077
0.6196 Remote Similarity NPC473597
0.6119 Remote Similarity NPC333075
0.6119 Remote Similarity NPC274499
0.6119 Remote Similarity NPC8488
0.6118 Remote Similarity NPC472351
0.6087 Remote Similarity NPC117829
0.6071 Remote Similarity NPC6902
0.6064 Remote Similarity NPC475440
0.6064 Remote Similarity NPC475758
0.6022 Remote Similarity NPC134504
0.6022 Remote Similarity NPC47076
0.6 Remote Similarity NPC13175
0.6 Remote Similarity NPC87359
0.6 Remote Similarity NPC180402
0.6 Remote Similarity NPC475791
0.5976 Remote Similarity NPC325902
0.5952 Remote Similarity NPC23984
0.5895 Remote Similarity NPC475188
0.5882 Remote Similarity NPC284456
0.5876 Remote Similarity NPC471097
0.5876 Remote Similarity NPC475149
0.587 Remote Similarity NPC301010
0.5867 Remote Similarity NPC160661
0.5843 Remote Similarity NPC473495
0.5833 Remote Similarity NPC292299
0.5833 Remote Similarity NPC34838
0.5816 Remote Similarity NPC476877
0.5814 Remote Similarity NPC235078
0.5811 Remote Similarity NPC105297
0.5806 Remote Similarity NPC280066
0.5758 Remote Similarity NPC323720
0.5758 Remote Similarity NPC128303
0.5753 Remote Similarity NPC263207
0.5729 Remote Similarity NPC220234
0.57 Remote Similarity NPC475637
0.57 Remote Similarity NPC241394
0.57 Remote Similarity NPC476876
0.5694 Remote Similarity NPC11433
0.5694 Remote Similarity NPC245346
0.5694 Remote Similarity NPC302003
0.5667 Remote Similarity NPC25237
0.5667 Remote Similarity NPC150560
0.5658 Remote Similarity NPC128559
0.5658 Remote Similarity NPC262615
0.5652 Remote Similarity NPC137327
0.5616 Remote Similarity NPC254541

  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 NPC128005 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
0.8 Intermediate Similarity NPD2683 Discontinued
0.7681 Intermediate Similarity NPD322 Phase 1
0.7619 Intermediate Similarity NPD1456 Approved
0.75 Intermediate Similarity NPD9425 Approved
0.7403 Intermediate Similarity NPD7762 Phase 2
0.7403 Intermediate Similarity NPD7763 Phase 2
0.7089 Intermediate Similarity NPD1125 Discovery
0.6951 Remote Similarity NPD7759 Phase 2
0.6951 Remote Similarity NPD3723 Clinical (unspecified phase)
0.6951 Remote Similarity NPD7760 Phase 2
0.6914 Remote Similarity NPD9577 Approved
0.6849 Remote Similarity NPD620 Approved
0.6786 Remote Similarity NPD3177 Phase 3
0.6716 Remote Similarity NPD581 Approved
0.6716 Remote Similarity NPD583 Approved
0.6716 Remote Similarity NPD843 Clinical (unspecified phase)
0.6716 Remote Similarity NPD584 Approved
0.6552 Remote Similarity NPD4780 Clinical (unspecified phase)
0.6552 Remote Similarity NPD4261 Phase 1
0.6533 Remote Similarity NPD2220 Clinical (unspecified phase)
0.6533 Remote Similarity NPD9649 Approved
0.6508 Remote Similarity NPD362 Phase 1
0.6456 Remote Similarity NPD9199 Approved
0.6406 Remote Similarity NPD8950 Approved
0.6316 Remote Similarity NPD1439 Clinical (unspecified phase)
0.6264 Remote Similarity NPD7841 Clinical (unspecified phase)
0.6203 Remote Similarity NPD9198 Approved
0.6163 Remote Similarity NPD5791 Phase 2
0.6154 Remote Similarity NPD266 Phase 3
0.6154 Remote Similarity NPD265 Phase 3
0.6129 Remote Similarity NPD8038 Phase 2
0.6098 Remote Similarity NPD4815 Discontinued
0.6087 Remote Similarity NPD9105 Phase 2
0.6023 Remote Similarity NPD867 Phase 3
0.6023 Remote Similarity NPD868 Phase 3
0.5979 Remote Similarity NPD6122 Discontinued
0.5851 Remote Similarity NPD1784 Approved
0.5833 Remote Similarity NPD9670 Phase 2
0.5833 Remote Similarity NPD8951 Approved
0.5833 Remote Similarity NPD9671 Phase 2
0.5824 Remote Similarity NPD2682 Approved
0.5824 Remote Similarity NPD5792 Clinical (unspecified phase)
0.5811 Remote Similarity NPD9625 Approved
0.5802 Remote Similarity NPD9367 Discontinued
0.5694 Remote Similarity NPD8865 Approved
0.5658 Remote Similarity NPD6437 Approved
0.5658 Remote Similarity NPD6438 Approved
0.5647 Remote Similarity NPD9578 Clinical (unspecified phase)
0.5644 Remote Similarity NPD6937 Approved
0.5625 Remote Similarity NPD5386 Phase 2

  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