Structure

Physi-Chem Properties

Molecular Weight:  226.13
Volume:  224.791
LogP:  0.424
LogD:  0.067
LogS:  -1.479
# Rotatable Bonds:  2
TPSA:  69.64
# H-Bond Aceptor:  5
# H-Bond Donor:  2
# Rings:  2
# Heavy Atoms:  5

MedChem Properties

QED Drug-Likeness Score:  0.666
Synthetic Accessibility Score:  3.449
Fsp3:  0.818
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:  -4.872
MDCK Permeability:  0.0002859397209249437
Pgp-inhibitor:  0.0
Pgp-substrate:  0.102
Human Intestinal Absorption (HIA):  0.069
20% Bioavailability (F20%):  0.003
30% Bioavailability (F30%):  0.004

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.211
Plasma Protein Binding (PPB):  5.36397647857666%
Volume Distribution (VD):  0.696
Pgp-substrate:  82.3333511352539%

ADMET: Metabolism

CYP1A2-inhibitor:  0.016
CYP1A2-substrate:  0.084
CYP2C19-inhibitor:  0.046
CYP2C19-substrate:  0.669
CYP2C9-inhibitor:  0.019
CYP2C9-substrate:  0.603
CYP2D6-inhibitor:  0.007
CYP2D6-substrate:  0.177
CYP3A4-inhibitor:  0.021
CYP3A4-substrate:  0.218

ADMET: Excretion

Clearance (CL):  5.881
Half-life (T1/2):  0.61

ADMET: Toxicity

hERG Blockers:  0.011
Human Hepatotoxicity (H-HT):  0.866
Drug-inuced Liver Injury (DILI):  0.339
AMES Toxicity:  0.013
Rat Oral Acute Toxicity:  0.174
Maximum Recommended Daily Dose:  0.358
Skin Sensitization:  0.122
Carcinogencity:  0.042
Eye Corrosion:  0.003
Eye Irritation:  0.021
Respiratory Toxicity:  0.068

Download Data

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

  Natural Product: NPC470783

Natural Product ID:  NPC470783
Common Name*:   (3S,8As)-7-Hydroxy-3-Isobutylhexahydropyrrolo[1,2-A]Pyrazine-1,4-Dione
IUPAC Name:   (3S,8aS)-7-hydroxy-3-(2-methylpropyl)-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
Synonyms:  
Standard InCHIKey:  YEHIUWVXPQQDMC-NPPUSCPJSA-N
Standard InCHI:  InChI=1S/C11H18N2O3/c1-6(2)3-8-11(16)13-5-7(14)4-9(13)10(15)12-8/h6-9,14H,3-5H2,1-2H3,(H,12,15)/t7?,8-,9-/m0/s1
SMILES:  CC(C[C@@H]1N=C(O)[C@H]2N(C1=O)CC(C2)O)C
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL2229109
PubChem CID:   14326059
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[511244]

☑ 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 NPC470783 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
0.9211 High Similarity NPC312315
0.9054 High Similarity NPC161774
0.9054 High Similarity NPC126186
0.9054 High Similarity NPC266888
0.9054 High Similarity NPC256312
0.88 High Similarity NPC209156
0.8784 High Similarity NPC76297
0.8784 High Similarity NPC196007
0.8784 High Similarity NPC214532
0.8571 High Similarity NPC470782
0.8289 Intermediate Similarity NPC470781
0.8108 Intermediate Similarity NPC128005
0.8108 Intermediate Similarity NPC84182
0.7841 Intermediate Similarity NPC475801
0.7841 Intermediate Similarity NPC474593
0.7805 Intermediate Similarity NPC31756
0.7753 Intermediate Similarity NPC474576
0.7711 Intermediate Similarity NPC476137
0.7711 Intermediate Similarity NPC476156
0.7711 Intermediate Similarity NPC476117
0.7711 Intermediate Similarity NPC476243
0.7703 Intermediate Similarity NPC243964
0.7667 Intermediate Similarity NPC173763
0.7667 Intermediate Similarity NPC471098
0.7667 Intermediate Similarity NPC62263
0.7619 Intermediate Similarity NPC476302
0.7412 Intermediate Similarity NPC475542
0.7386 Intermediate Similarity NPC477539
0.734 Intermediate Similarity NPC473597
0.7333 Intermediate Similarity NPC275715
0.7188 Intermediate Similarity NPC475440
0.7172 Intermediate Similarity NPC128303
0.7158 Intermediate Similarity NPC47076
0.7158 Intermediate Similarity NPC134504
0.7108 Intermediate Similarity NPC327272
0.71 Intermediate Similarity NPC241394
0.7071 Intermediate Similarity NPC476877
0.6941 Remote Similarity NPC59867
0.6931 Remote Similarity NPC476876
0.6867 Remote Similarity NPC29326
0.6837 Remote Similarity NPC475758
0.6809 Remote Similarity NPC477538
0.68 Remote Similarity NPC471097
0.68 Remote Similarity NPC475149
0.6768 Remote Similarity NPC13175
0.6768 Remote Similarity NPC475791
0.6765 Remote Similarity NPC475637
0.6667 Remote Similarity NPC325902
0.6667 Remote Similarity NPC220234
0.6636 Remote Similarity NPC63191
0.6636 Remote Similarity NPC471202
0.6625 Remote Similarity NPC160661
0.6604 Remote Similarity NPC476875
0.6556 Remote Similarity NPC84128
0.6556 Remote Similarity NPC53858
0.6552 Remote Similarity NPC329077
0.6506 Remote Similarity NPC322274
0.6505 Remote Similarity NPC323720
0.6471 Remote Similarity NPC5864
0.6471 Remote Similarity NPC301148
0.6471 Remote Similarity NPC124554
0.6421 Remote Similarity NPC322966
0.6413 Remote Similarity NPC472351
0.6408 Remote Similarity NPC198344
0.6392 Remote Similarity NPC315237
0.6374 Remote Similarity NPC184473
0.6372 Remote Similarity NPC315188
0.6364 Remote Similarity NPC296043
0.6346 Remote Similarity NPC124549
0.6341 Remote Similarity NPC287693
0.6339 Remote Similarity NPC469899
0.6321 Remote Similarity NPC67009
0.6321 Remote Similarity NPC207820
0.6306 Remote Similarity NPC329216
0.6267 Remote Similarity NPC137327
0.6264 Remote Similarity NPC23984
0.625 Remote Similarity NPC314510
0.6228 Remote Similarity NPC160688
0.6207 Remote Similarity NPC320221
0.6196 Remote Similarity NPC6902
0.617 Remote Similarity NPC325723
0.6168 Remote Similarity NPC171734
0.6162 Remote Similarity NPC301010
0.6154 Remote Similarity NPC474082
0.6154 Remote Similarity NPC175726
0.6146 Remote Similarity NPC324506
0.6129 Remote Similarity NPC235078
0.6122 Remote Similarity NPC476019
0.61 Remote Similarity NPC280066
0.6098 Remote Similarity NPC57420
0.604 Remote Similarity NPC469739
0.604 Remote Similarity NPC117829
0.6024 Remote Similarity NPC41429
0.6024 Remote Similarity NPC128559
0.6022 Remote Similarity NPC246005
0.6022 Remote Similarity NPC284456
0.6019 Remote Similarity NPC475188
0.6019 Remote Similarity NPC296143
0.6 Remote Similarity NPC470652
0.5983 Remote Similarity NPC50520
0.5979 Remote Similarity NPC473495
0.5976 Remote Similarity NPC105297
0.5946 Remote Similarity NPC87359
0.5946 Remote Similarity NPC180402
0.5932 Remote Similarity NPC470654
0.5932 Remote Similarity NPC470653
0.5932 Remote Similarity NPC470650
0.5918 Remote Similarity NPC155230
0.5909 Remote Similarity NPC251122
0.5905 Remote Similarity NPC188785
0.5897 Remote Similarity NPC275727
0.5882 Remote Similarity NPC196359
0.5882 Remote Similarity NPC78312
0.5882 Remote Similarity NPC135539
0.5882 Remote Similarity NPC221764
0.5876 Remote Similarity NPC210456
0.5876 Remote Similarity NPC163352
0.5843 Remote Similarity NPC263281
0.5833 Remote Similarity NPC472609
0.5833 Remote Similarity NPC277918
0.5825 Remote Similarity NPC313821
0.5816 Remote Similarity NPC52533
0.5802 Remote Similarity NPC321468
0.5802 Remote Similarity NPC327748
0.5789 Remote Similarity NPC271115
0.5776 Remote Similarity NPC477237
0.5761 Remote Similarity NPC37681
0.5761 Remote Similarity NPC233108
0.575 Remote Similarity NPC317147
0.5732 Remote Similarity NPC329564
0.5732 Remote Similarity NPC327170
0.5714 Remote Similarity NPC322946
0.5714 Remote Similarity NPC471131
0.5698 Remote Similarity NPC59221
0.5684 Remote Similarity NPC319753
0.5682 Remote Similarity NPC476285
0.5682 Remote Similarity NPC478256
0.5678 Remote Similarity NPC477238
0.5667 Remote Similarity NPC178919
0.5667 Remote Similarity NPC315806
0.5657 Remote Similarity NPC168017
0.5656 Remote Similarity NPC470651
0.5656 Remote Similarity NPC470655
0.5652 Remote Similarity NPC472594
0.5647 Remote Similarity NPC233034
0.5632 Remote Similarity NPC254617
0.5632 Remote Similarity NPC306696
0.5632 Remote Similarity NPC74555
0.5632 Remote Similarity NPC306763
0.5632 Remote Similarity NPC266242
0.562 Remote Similarity NPC6975
0.5614 Remote Similarity NPC309731
0.5612 Remote Similarity NPC89051
0.5612 Remote Similarity NPC43246
0.561 Remote Similarity NPC316826
0.561 Remote Similarity NPC317143
0.5603 Remote Similarity NPC28542
0.56 Remote Similarity NPC171116

  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 NPC470783 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
0.8171 Intermediate Similarity NPD2683 Discontinued
0.7791 Intermediate Similarity NPD3723 Clinical (unspecified phase)
0.7416 Intermediate Similarity NPD3177 Phase 3
0.7412 Intermediate Similarity NPD7762 Phase 2
0.7412 Intermediate Similarity NPD7763 Phase 2
0.7234 Intermediate Similarity NPD7841 Clinical (unspecified phase)
0.7191 Intermediate Similarity NPD7760 Phase 2
0.7191 Intermediate Similarity NPD7759 Phase 2
0.7126 Intermediate Similarity NPD1125 Discovery
0.7125 Intermediate Similarity NPD620 Approved
0.7083 Intermediate Similarity NPD8038 Phase 2
0.7 Intermediate Similarity NPD322 Phase 1
0.6989 Remote Similarity NPD4261 Phase 1
0.6809 Remote Similarity NPD4780 Clinical (unspecified phase)
0.6733 Remote Similarity NPD6122 Discontinued
0.6667 Remote Similarity NPD1456 Approved
0.6364 Remote Similarity NPD9425 Approved
0.6237 Remote Similarity NPD9577 Approved
0.6235 Remote Similarity NPD9649 Approved
0.6235 Remote Similarity NPD1439 Clinical (unspecified phase)
0.6222 Remote Similarity NPD4815 Discontinued
0.6203 Remote Similarity NPD8951 Approved
0.6132 Remote Similarity NPD1385 Discontinued
0.6122 Remote Similarity NPD2682 Approved
0.6105 Remote Similarity NPD5791 Phase 2
0.6078 Remote Similarity NPD3715 Approved
0.6078 Remote Similarity NPD3714 Approved
0.6078 Remote Similarity NPD3713 Approved
0.6075 Remote Similarity NPD6937 Approved
0.6064 Remote Similarity NPD3733 Clinical (unspecified phase)
0.6047 Remote Similarity NPD2220 Clinical (unspecified phase)
0.596 Remote Similarity NPD5792 Clinical (unspecified phase)
0.5909 Remote Similarity NPD266 Phase 3
0.5909 Remote Similarity NPD265 Phase 3
0.59 Remote Similarity NPD6699 Clinical (unspecified phase)
0.5882 Remote Similarity NPD8868 Approved
0.5833 Remote Similarity NPD9401 Discovery
0.5825 Remote Similarity NPD1784 Approved
0.5825 Remote Similarity NPD3191 Approved
0.5825 Remote Similarity NPD3190 Approved
0.5825 Remote Similarity NPD3189 Approved
0.581 Remote Similarity NPD6120 Clinical (unspecified phase)
0.5802 Remote Similarity NPD9670 Phase 2
0.5802 Remote Similarity NPD9671 Phase 2
0.5766 Remote Similarity NPD1804 Phase 2
0.5766 Remote Similarity NPD1805 Phase 2
0.5758 Remote Similarity NPD755 Phase 3
0.5758 Remote Similarity NPD841 Approved
0.575 Remote Similarity NPD581 Approved
0.575 Remote Similarity NPD584 Approved
0.575 Remote Similarity NPD843 Clinical (unspecified phase)
0.575 Remote Similarity NPD583 Approved
0.5733 Remote Similarity NPD362 Phase 1
0.5714 Remote Similarity NPD9441 Phase 2
0.5714 Remote Similarity NPD3176 Clinical (unspecified phase)
0.5702 Remote Similarity NPD7915 Approved
0.5702 Remote Similarity NPD7916 Approved
0.5698 Remote Similarity NPD2263 Discontinued
0.5682 Remote Similarity NPD2697 Approved
0.5682 Remote Similarity NPD2695 Approved
0.5682 Remote Similarity NPD2694 Approved
0.5682 Remote Similarity NPD2696 Approved
0.5667 Remote Similarity NPD9653 Clinical (unspecified phase)
0.566 Remote Similarity NPD5359 Clinical (unspecified phase)
0.5648 Remote Similarity NPD2633 Phase 1
0.5647 Remote Similarity NPD9440 Discontinued
0.5644 Remote Similarity NPD251 Approved
0.5638 Remote Similarity NPD9578 Clinical (unspecified phase)
0.563 Remote Similarity NPD7652 Discontinued
0.5625 Remote Similarity NPD883 Phase 2
0.5625 Remote Similarity NPD882 Phase 2
0.5612 Remote Similarity NPD9580 Clinical (unspecified phase)
0.5612 Remote Similarity NPD9581 Clinical (unspecified phase)
0.561 Remote Similarity NPD354 Approved
0.5607 Remote Similarity NPD7651 Approved

  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