Structure

Physi-Chem Properties

Molecular Weight:  154.07
Volume:  146.816
LogP:  -1.077
LogD:  -1.3
LogS:  -1.057
# 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:  0.492
Synthetic Accessibility Score:  2.884
Fsp3:  0.714
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:  -4.872
MDCK Permeability:  7.077272584865568e-06
Pgp-inhibitor:  0.003
Pgp-substrate:  0.013
Human Intestinal Absorption (HIA):  0.06
20% Bioavailability (F20%):  0.111
30% Bioavailability (F30%):  0.25

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.987
Plasma Protein Binding (PPB):  8.194231033325195%
Volume Distribution (VD):  0.819
Pgp-substrate:  86.91584777832031%

ADMET: Metabolism

CYP1A2-inhibitor:  0.012
CYP1A2-substrate:  0.107
CYP2C19-inhibitor:  0.034
CYP2C19-substrate:  0.191
CYP2C9-inhibitor:  0.034
CYP2C9-substrate:  0.305
CYP2D6-inhibitor:  0.005
CYP2D6-substrate:  0.217
CYP3A4-inhibitor:  0.008
CYP3A4-substrate:  0.069

ADMET: Excretion

Clearance (CL):  5.695
Half-life (T1/2):  0.697

ADMET: Toxicity

hERG Blockers:  0.008
Human Hepatotoxicity (H-HT):  0.386
Drug-inuced Liver Injury (DILI):  0.036
AMES Toxicity:  0.009
Rat Oral Acute Toxicity:  0.146
Maximum Recommended Daily Dose:  0.085
Skin Sensitization:  0.265
Carcinogencity:  0.02
Eye Corrosion:  0.005
Eye Irritation:  0.037
Respiratory Toxicity:  0.05

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

  Natural Product: NPC243964

Natural Product ID:  NPC243964
Common Name*:   Cyclo-(Glycyl-L-Prolyl)
IUPAC Name:   (8aS)-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
Synonyms:  
Standard InCHIKey:  OWOHLURDBZHNGG-YFKPBYRVSA-N
Standard InCHI:  InChI=1S/C7H10N2O2/c10-6-4-8-7(11)5-2-1-3-9(5)6/h5H,1-4H2,(H,8,11)/t5-/m0/s1
SMILES:  C1C[C@H]2C(=NCC(=O)N2C1)O
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL360216
PubChem CID:   126154
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
NPO33070 Callyspongia sp. Species n.a. n.a. n.a. red sea n.a. PMID[12762806]
NPO20897.1 Suberites domuncula Under-species n.a. n.a. n.a. n.a. n.a. PMID[15270577]
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]
NPO33070 Callyspongia sp. Species n.a. n.a. n.a. n.a. n.a. PMID[18027906]
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]
NPO33070 Callyspongia sp. Species n.a. n.a. n.a. n.a. n.a. PMID[22469701]
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]
NPO33070 Callyspongia sp. Species n.a. n.a. n.a. collected by hand at a depth of 10 m off the shore of Iriomote Island, Okinawa Prefecture, Japan 2009-JUN PMID[23855338]
NPO33070 Callyspongia sp. Species n.a. n.a. n.a. n.a. n.a. PMID[24948562]
NPO33070 Callyspongia sp. Species n.a. n.a. n.a. n.a. n.a. PMID[27015002]
NPO10538 Aspergillus fumigatus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[7622436]
NPO33070 Callyspongia sp. Species n.a. n.a. n.a. New Guinea n.a. PMID[8158156]
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
NPT1182 Cell Line J774.A1 Mus musculus FC = 1.29 n.a. PMID[468310]
NPT1182 Cell Line J774.A1 Mus musculus FC = 3.5 n.a. PMID[468310]
NPT1182 Cell Line J774.A1 Mus musculus FC = 1.86 n.a. PMID[468310]
NPT113 Cell Line RAW264.7 Mus musculus Inhibition = 39.7 % PMID[468312]
NPT113 Cell Line RAW264.7 Mus musculus IC50 = 4.5 ug.mL-1 PMID[468312]
NPT113 Cell Line RAW264.7 Mus musculus Inhibition = 3.0 % PMID[468312]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae Cell aggregates = 75.7 n.a. PMID[468308]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae Cell aggregates = 33.2 n.a. PMID[468308]
NPT176 Organism Artemia salina Artemia salina LC50 > 100.0 ug.mL-1 PMID[468311]

☑ 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 NPC243964 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
0.95 High Similarity NPC84182
0.95 High Similarity NPC128005
0.8769 High Similarity NPC214532
0.8769 High Similarity NPC76297
0.8769 High Similarity NPC470781
0.8769 High Similarity NPC196007
0.8507 High Similarity NPC209156
0.8507 High Similarity NPC266888
0.8507 High Similarity NPC126186
0.8507 High Similarity NPC256312
0.8507 High Similarity NPC161774
0.8261 Intermediate Similarity NPC470782
0.7917 Intermediate Similarity NPC312315
0.7703 Intermediate Similarity NPC470783
0.7397 Intermediate Similarity NPC59867
0.7206 Intermediate Similarity NPC287693
0.72 Intermediate Similarity NPC31756
0.7105 Intermediate Similarity NPC476117
0.7105 Intermediate Similarity NPC476156
0.7105 Intermediate Similarity NPC476243
0.7105 Intermediate Similarity NPC476137
0.7013 Intermediate Similarity NPC475542
0.7013 Intermediate Similarity NPC476302
0.6901 Remote Similarity NPC322274
0.6585 Remote Similarity NPC477539
0.6533 Remote Similarity NPC320221
0.6447 Remote Similarity NPC327272
0.6353 Remote Similarity NPC275715
0.6282 Remote Similarity NPC329077
0.6279 Remote Similarity NPC474593
0.6279 Remote Similarity NPC475801
0.6207 Remote Similarity NPC474576
0.6207 Remote Similarity NPC477538
0.6184 Remote Similarity NPC29326
0.6143 Remote Similarity NPC314510
0.6136 Remote Similarity NPC471098
0.6136 Remote Similarity NPC173763
0.6136 Remote Similarity NPC62263
0.6098 Remote Similarity NPC184473
0.5972 Remote Similarity NPC57420
0.5965 Remote Similarity NPC150560
0.5909 Remote Similarity NPC274499
0.5909 Remote Similarity NPC333075
0.5909 Remote Similarity NPC8488
0.5904 Remote Similarity NPC53858
0.5904 Remote Similarity NPC84128
0.587 Remote Similarity NPC473597
0.5846 Remote Similarity NPC327239
0.5802 Remote Similarity NPC325902
0.5781 Remote Similarity NPC87359
0.5781 Remote Similarity NPC180402
0.5765 Remote Similarity NPC472351
0.5761 Remote Similarity NPC117829
0.5745 Remote Similarity NPC475758
0.5745 Remote Similarity NPC475440
0.5735 Remote Similarity NPC275727
0.5714 Remote Similarity NPC302003
0.5714 Remote Similarity NPC245346
0.5714 Remote Similarity NPC11433
0.5714 Remote Similarity NPC6902
0.5699 Remote Similarity NPC134504
0.5699 Remote Similarity NPC47076
0.569 Remote Similarity NPC25237
0.5684 Remote Similarity NPC13175
0.5684 Remote Similarity NPC475791
0.5676 Remote Similarity NPC160661
0.5634 Remote Similarity NPC34838
0.5634 Remote Similarity NPC292299

  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 NPC243964 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
0.76 Intermediate Similarity NPD2683 Discontinued
0.75 Intermediate Similarity NPD322 Phase 1
0.7143 Intermediate Similarity NPD1456 Approved
0.7031 Intermediate Similarity NPD9425 Approved
0.7013 Intermediate Similarity NPD7763 Phase 2
0.7013 Intermediate Similarity NPD7762 Phase 2
0.675 Remote Similarity NPD9577 Approved
0.6711 Remote Similarity NPD9199 Approved
0.6709 Remote Similarity NPD1125 Discovery
0.6585 Remote Similarity NPD7760 Phase 2
0.6585 Remote Similarity NPD3723 Clinical (unspecified phase)
0.6585 Remote Similarity NPD7759 Phase 2
0.6515 Remote Similarity NPD581 Approved
0.6515 Remote Similarity NPD843 Clinical (unspecified phase)
0.6515 Remote Similarity NPD584 Approved
0.6515 Remote Similarity NPD583 Approved
0.6452 Remote Similarity NPD8950 Approved
0.6447 Remote Similarity NPD9198 Approved
0.6438 Remote Similarity NPD620 Approved
0.6429 Remote Similarity NPD3177 Phase 3
0.6351 Remote Similarity NPD2220 Clinical (unspecified phase)
0.629 Remote Similarity NPD362 Phase 1
0.6207 Remote Similarity NPD4261 Phase 1
0.6207 Remote Similarity NPD4780 Clinical (unspecified phase)
0.6133 Remote Similarity NPD1439 Clinical (unspecified phase)
0.6133 Remote Similarity NPD9649 Approved
0.6119 Remote Similarity NPD9105 Phase 2
0.6047 Remote Similarity NPD868 Phase 3
0.6047 Remote Similarity NPD867 Phase 3
0.5934 Remote Similarity NPD7841 Clinical (unspecified phase)
0.5857 Remote Similarity NPD8951 Approved
0.5814 Remote Similarity NPD5791 Phase 2
0.5806 Remote Similarity NPD8038 Phase 2
0.5769 Remote Similarity NPD266 Phase 3
0.5769 Remote Similarity NPD265 Phase 3
0.5732 Remote Similarity NPD4815 Discontinued
0.5714 Remote Similarity NPD8865 Approved
0.567 Remote Similarity NPD6122 Discontinued
0.5641 Remote Similarity NPD5386 Phase 2
0.5625 Remote Similarity NPD9367 Discontinued

  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