Structure

Physi-Chem Properties

Molecular Weight:  184.08
Volume:  172.903
LogP:  -1.276
LogD:  -1.663
LogS:  -0.955
# Rotatable Bonds:  1
TPSA:  69.64
# H-Bond Aceptor:  5
# H-Bond Donor:  2
# Rings:  2
# Heavy Atoms:  5

MedChem Properties

QED Drug-Likeness Score:  0.519
Synthetic Accessibility Score:  3.122
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:  -5.475
MDCK Permeability:  0.0007222319254651666
Pgp-inhibitor:  0.001
Pgp-substrate:  0.009
Human Intestinal Absorption (HIA):  0.453
20% Bioavailability (F20%):  0.389
30% Bioavailability (F30%):  0.074

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.401
Plasma Protein Binding (PPB):  7.1720476150512695%
Volume Distribution (VD):  0.532
Pgp-substrate:  86.6888427734375%

ADMET: Metabolism

CYP1A2-inhibitor:  0.008
CYP1A2-substrate:  0.1
CYP2C19-inhibitor:  0.025
CYP2C19-substrate:  0.162
CYP2C9-inhibitor:  0.011
CYP2C9-substrate:  0.65
CYP2D6-inhibitor:  0.003
CYP2D6-substrate:  0.18
CYP3A4-inhibitor:  0.006
CYP3A4-substrate:  0.05

ADMET: Excretion

Clearance (CL):  3.377
Half-life (T1/2):  0.773

ADMET: Toxicity

hERG Blockers:  0.008
Human Hepatotoxicity (H-HT):  0.503
Drug-inuced Liver Injury (DILI):  0.181
AMES Toxicity:  0.012
Rat Oral Acute Toxicity:  0.126
Maximum Recommended Daily Dose:  0.02
Skin Sensitization:  0.23
Carcinogencity:  0.027
Eye Corrosion:  0.003
Eye Irritation:  0.026
Respiratory Toxicity:  0.033

Download Data

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

  Natural Product: NPC470781

Natural Product ID:  NPC470781
Common Name*:   (3S,8As)-3-(Hydroxymethyl)Hexahydropyrrolo[1,2-A]Pyrazine-1,4-Dione
IUPAC Name:   (3S,8aS)-3-(hydroxymethyl)-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
Synonyms:  
Standard InCHIKey:  AHTDIKDEEMDJGD-WDSKDSINSA-N
Standard InCHI:  InChI=1S/C8H12N2O3/c11-4-5-8(13)10-3-1-2-6(10)7(12)9-5/h5-6,11H,1-4H2,(H,9,12)/t5-,6-/m0/s1
SMILES:  C1CC2C(=O)NC(C(=O)N2C1)CO
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL2229107
PubChem CID:   44185776
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[537931]

☑ 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 NPC470781 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
0.942 High Similarity NPC470782
0.913 High Similarity NPC126186
0.8939 High Similarity NPC128005
0.8939 High Similarity NPC84182
0.8769 High Similarity NPC243964
0.831 Intermediate Similarity NPC214532
0.831 Intermediate Similarity NPC76297
0.831 Intermediate Similarity NPC196007
0.8289 Intermediate Similarity NPC470783
0.8267 Intermediate Similarity NPC312315
0.8082 Intermediate Similarity NPC209156
0.8082 Intermediate Similarity NPC266888
0.8082 Intermediate Similarity NPC161774
0.8082 Intermediate Similarity NPC256312
0.8052 Intermediate Similarity NPC475542
0.7564 Intermediate Similarity NPC31756
0.7468 Intermediate Similarity NPC476156
0.7468 Intermediate Similarity NPC476137
0.7468 Intermediate Similarity NPC476117
0.7468 Intermediate Similarity NPC476243
0.7375 Intermediate Similarity NPC476302
0.7089 Intermediate Similarity NPC59867
0.6941 Remote Similarity NPC477539
0.6897 Remote Similarity NPC275715
0.6795 Remote Similarity NPC29326
0.6667 Remote Similarity NPC287693
0.6667 Remote Similarity NPC329077
0.6629 Remote Similarity NPC475801
0.6629 Remote Similarity NPC474593
0.6623 Remote Similarity NPC322274
0.6556 Remote Similarity NPC474576
0.6484 Remote Similarity NPC62263
0.6484 Remote Similarity NPC173763
0.6484 Remote Similarity NPC471098
0.6383 Remote Similarity NPC134504
0.6383 Remote Similarity NPC473597
0.6383 Remote Similarity NPC47076
0.6374 Remote Similarity NPC477538
0.6327 Remote Similarity NPC476877
0.6296 Remote Similarity NPC320221
0.622 Remote Similarity NPC327272
0.62 Remote Similarity NPC476876
0.619 Remote Similarity NPC325902
0.6104 Remote Similarity NPC160661
0.6082 Remote Similarity NPC475440
0.6082 Remote Similarity NPC475758
0.602 Remote Similarity NPC475791
0.602 Remote Similarity NPC13175
0.5974 Remote Similarity NPC57420
0.5972 Remote Similarity NPC275727
0.5941 Remote Similarity NPC128303
0.5909 Remote Similarity NPC184473
0.5905 Remote Similarity NPC476875
0.59 Remote Similarity NPC471097
0.59 Remote Similarity NPC475149
0.5882 Remote Similarity NPC475637
0.5882 Remote Similarity NPC241394
0.573 Remote Similarity NPC53858
0.573 Remote Similarity NPC84128
0.573 Remote Similarity NPC319753
0.5714 Remote Similarity NPC325723
0.5714 Remote Similarity NPC314510
0.5696 Remote Similarity NPC233034
0.5694 Remote Similarity NPC137327
0.5688 Remote Similarity NPC296043
0.5652 Remote Similarity NPC89051
0.5652 Remote Similarity NPC43246
0.5638 Remote Similarity NPC322966
0.5636 Remote Similarity NPC329216
0.5631 Remote Similarity NPC323720
0.5625 Remote Similarity NPC315237
0.5619 Remote Similarity NPC67009
0.5616 Remote Similarity NPC272396
0.5612 Remote Similarity NPC117829
0.5604 Remote Similarity NPC472351
0.56 Remote Similarity NPC475188
0.56 Remote Similarity NPC220234

  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 NPC470781 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
0.7381 Intermediate Similarity NPD3177 Phase 3
0.7284 Intermediate Similarity NPD2683 Discontinued
0.7162 Intermediate Similarity NPD322 Phase 1
0.6941 Remote Similarity NPD3723 Clinical (unspecified phase)
0.6812 Remote Similarity NPD1456 Approved
0.6761 Remote Similarity NPD8951 Approved
0.6747 Remote Similarity NPD7763 Phase 2
0.6747 Remote Similarity NPD7762 Phase 2
0.6742 Remote Similarity NPD4261 Phase 1
0.6742 Remote Similarity NPD4780 Clinical (unspecified phase)
0.6714 Remote Similarity NPD9425 Approved
0.6512 Remote Similarity NPD9577 Approved
0.6471 Remote Similarity NPD1125 Discovery
0.6364 Remote Similarity NPD7760 Phase 2
0.6364 Remote Similarity NPD7759 Phase 2
0.6316 Remote Similarity NPD8038 Phase 2
0.6277 Remote Similarity NPD7841 Clinical (unspecified phase)
0.6203 Remote Similarity NPD620 Approved
0.6162 Remote Similarity NPD6122 Discontinued
0.6125 Remote Similarity NPD2220 Clinical (unspecified phase)
0.6071 Remote Similarity NPD9199 Approved
0.6027 Remote Similarity NPD584 Approved
0.6027 Remote Similarity NPD581 Approved
0.6027 Remote Similarity NPD843 Clinical (unspecified phase)
0.6027 Remote Similarity NPD583 Approved
0.5942 Remote Similarity NPD8950 Approved
0.5926 Remote Similarity NPD1439 Clinical (unspecified phase)
0.5926 Remote Similarity NPD9649 Approved
0.5889 Remote Similarity NPD9401 Discovery
0.5844 Remote Similarity NPD9625 Approved
0.5833 Remote Similarity NPD9198 Approved
0.5797 Remote Similarity NPD362 Phase 1
0.5699 Remote Similarity NPD868 Phase 3
0.5699 Remote Similarity NPD867 Phase 3
0.5696 Remote Similarity NPD9440 Discontinued
0.5676 Remote Similarity NPD9105 Phase 2
0.5652 Remote Similarity NPD5791 Phase 2
0.5652 Remote Similarity NPD9580 Clinical (unspecified phase)
0.5652 Remote Similarity NPD9581 Clinical (unspecified phase)
0.5618 Remote Similarity NPD3628 Phase 3

  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