Structure

Physi-Chem Properties

Molecular Weight:  616.4
Volume:  654.126
LogP:  6.876
LogD:  4.208
LogS:  -4.76
# Rotatable Bonds:  17
TPSA:  130.36
# H-Bond Aceptor:  8
# H-Bond Donor:  3
# Rings:  4
# Heavy Atoms:  8

MedChem Properties

QED Drug-Likeness Score:  0.12
Synthetic Accessibility Score:  4.975
Fsp3:  0.806
Lipinski Rule-of-5:  Rejected
Pfizer Rule:  Accepted
GSK Rule:  Rejected
BMS Rule:  1
Golden Triangle Rule:  Rejected
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -4.805
MDCK Permeability:  2.1929161448497325e-05
Pgp-inhibitor:  0.997
Pgp-substrate:  0.015
Human Intestinal Absorption (HIA):  0.057
20% Bioavailability (F20%):  0.996
30% Bioavailability (F30%):  0.98

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.499
Plasma Protein Binding (PPB):  96.02816772460938%
Volume Distribution (VD):  1.841
Pgp-substrate:  3.102752685546875%

ADMET: Metabolism

CYP1A2-inhibitor:  0.046
CYP1A2-substrate:  0.1
CYP2C19-inhibitor:  0.512
CYP2C19-substrate:  0.14
CYP2C9-inhibitor:  0.727
CYP2C9-substrate:  0.136
CYP2D6-inhibitor:  0.053
CYP2D6-substrate:  0.02
CYP3A4-inhibitor:  0.903
CYP3A4-substrate:  0.135

ADMET: Excretion

Clearance (CL):  2.941
Half-life (T1/2):  0.06

ADMET: Toxicity

hERG Blockers:  0.865
Human Hepatotoxicity (H-HT):  0.944
Drug-inuced Liver Injury (DILI):  0.41
AMES Toxicity:  0.024
Rat Oral Acute Toxicity:  0.883
Maximum Recommended Daily Dose:  0.903
Skin Sensitization:  0.908
Carcinogencity:  0.076
Eye Corrosion:  0.003
Eye Irritation:  0.01
Respiratory Toxicity:  0.978

Download Data

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

  Natural Product: NPC59867

Natural Product ID:  NPC59867
Common Name*:   Cyclo-(Glycyl-L-Prolyl-L-Glutamyl)
IUPAC Name:   3-[(3S,11aS)-1,4,7-trioxo-2,3,5,6,9,10,11,11a-octahydropyrrolo[1,2-a][1,4,7]triazonin-3-yl]propanoic acid
Synonyms:  
Standard InCHIKey:  VGNAMNNHMPYOHS-YUMQZZPRSA-N
Standard InCHI:  InChI=1S/C12H17N3O5/c16-9-6-13-11(19)7(3-4-10(17)18)14-12(20)8-2-1-5-15(8)9/h7-8H,1-6H2,(H,13,19)(H,14,20)(H,17,18)/t7-,8-/m0/s1
SMILES:  OC(=O)CC[C@@H]1N=C(O)[C@@H]2CCCN2C(=O)CN=C1O
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL449485
PubChem CID:   11277548
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:0000348] Peptides
            • [CHEMONTID:0001995] Cyclic peptides

*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
NPO20897.1 Suberites domuncula Under-species n.a. n.a. n.a. n.a. n.a. PMID[15270577]

☑ 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
NPT22 Organism Bacillus subtilis subsp. spizizenii Bacillus subtilis subsp. spizizenii MIC = 50.0 ug.mL-1 PMID[510598]

☑ 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 NPC59867 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
0.8701 High Similarity NPC475542
0.7568 Intermediate Similarity NPC84182
0.7568 Intermediate Similarity NPC128005
0.7564 Intermediate Similarity NPC209156
0.7564 Intermediate Similarity NPC256312
0.7564 Intermediate Similarity NPC161774
0.7564 Intermediate Similarity NPC266888
0.7532 Intermediate Similarity NPC76297
0.7532 Intermediate Similarity NPC214532
0.7532 Intermediate Similarity NPC196007
0.7531 Intermediate Similarity NPC312315
0.7397 Intermediate Similarity NPC243964
0.7333 Intermediate Similarity NPC287693
0.7273 Intermediate Similarity NPC322274
0.7125 Intermediate Similarity NPC320221
0.7089 Intermediate Similarity NPC470781
0.7059 Intermediate Similarity NPC53858
0.7059 Intermediate Similarity NPC84128
0.7037 Intermediate Similarity NPC327272
0.7 Intermediate Similarity NPC475801
0.7 Intermediate Similarity NPC474593
0.6951 Remote Similarity NPC470782
0.6941 Remote Similarity NPC470783
0.6923 Remote Similarity NPC474576
0.6914 Remote Similarity NPC126186
0.6905 Remote Similarity NPC31756
0.6848 Remote Similarity NPC173763
0.6848 Remote Similarity NPC62263
0.6848 Remote Similarity NPC471098
0.6824 Remote Similarity NPC476117
0.6824 Remote Similarity NPC476243
0.6824 Remote Similarity NPC476137
0.6824 Remote Similarity NPC476156
0.6771 Remote Similarity NPC475440
0.6744 Remote Similarity NPC476302
0.6667 Remote Similarity NPC143722
0.6623 Remote Similarity NPC57420
0.6562 Remote Similarity NPC473597
0.6559 Remote Similarity NPC477538
0.6533 Remote Similarity NPC321536
0.6494 Remote Similarity NPC327252
0.6458 Remote Similarity NPC117829
0.6438 Remote Similarity NPC322573
0.6389 Remote Similarity NPC263065
0.6389 Remote Similarity NPC189178
0.6374 Remote Similarity NPC477539
0.6351 Remote Similarity NPC325985
0.6344 Remote Similarity NPC275715
0.6275 Remote Similarity NPC323720
0.6263 Remote Similarity NPC475758
0.625 Remote Similarity NPC29950
0.625 Remote Similarity NPC19576
0.6238 Remote Similarity NPC475149
0.6238 Remote Similarity NPC471097
0.6214 Remote Similarity NPC475637
0.62 Remote Similarity NPC13175
0.62 Remote Similarity NPC475791
0.6164 Remote Similarity NPC333075
0.6164 Remote Similarity NPC274499
0.6164 Remote Similarity NPC8488
0.6133 Remote Similarity NPC38463
0.6125 Remote Similarity NPC325597
0.6125 Remote Similarity NPC174304
0.6111 Remote Similarity NPC184473
0.6111 Remote Similarity NPC327239
0.61 Remote Similarity NPC220234
0.6076 Remote Similarity NPC105297
0.6 Remote Similarity NPC29326
0.6 Remote Similarity NPC289691
0.5978 Remote Similarity NPC472351
0.5974 Remote Similarity NPC11433
0.5974 Remote Similarity NPC302003
0.5974 Remote Similarity NPC245346
0.5962 Remote Similarity NPC128303
0.5946 Remote Similarity NPC197087
0.5946 Remote Similarity NPC190184
0.5934 Remote Similarity NPC6902
0.5926 Remote Similarity NPC128559
0.5926 Remote Similarity NPC160661
0.5922 Remote Similarity NPC124554
0.5922 Remote Similarity NPC301148
0.5922 Remote Similarity NPC5864
0.5905 Remote Similarity NPC241394
0.5904 Remote Similarity NPC319046
0.5904 Remote Similarity NPC306696
0.59 Remote Similarity NPC47076
0.59 Remote Similarity NPC134504
0.5897 Remote Similarity NPC34838
0.5897 Remote Similarity NPC292299
0.5897 Remote Similarity NPC320598
0.5897 Remote Similarity NPC254541
0.5882 Remote Similarity NPC328457
0.5865 Remote Similarity NPC198344
0.5833 Remote Similarity NPC126779
0.5824 Remote Similarity NPC23984
0.5823 Remote Similarity NPC263207
0.5818 Remote Similarity NPC471202
0.5818 Remote Similarity NPC63191
0.581 Remote Similarity NPC124549
0.5769 Remote Similarity NPC176164
0.5769 Remote Similarity NPC189301
0.5761 Remote Similarity NPC284456
0.5743 Remote Similarity NPC144780
0.5729 Remote Similarity NPC473495
0.5699 Remote Similarity NPC235078
0.5696 Remote Similarity NPC321468
0.5696 Remote Similarity NPC327748
0.5696 Remote Similarity NPC316826
0.5696 Remote Similarity NPC317143
0.567 Remote Similarity NPC322966
0.5663 Remote Similarity NPC325534
0.5648 Remote Similarity NPC171734
0.5648 Remote Similarity NPC67009
0.5641 Remote Similarity NPC318260
0.5641 Remote Similarity NPC317147
0.5641 Remote Similarity NPC278209
0.5636 Remote Similarity NPC476875
0.5625 Remote Similarity NPC329564
0.5625 Remote Similarity NPC177191
0.5625 Remote Similarity NPC327170
0.56 Remote Similarity NPC322946
0.56 Remote Similarity NPC301010

  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 NPC59867 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
0.8354 Intermediate Similarity NPD1125 Discovery
0.7738 Intermediate Similarity NPD7760 Phase 2
0.7738 Intermediate Similarity NPD7759 Phase 2
0.7711 Intermediate Similarity NPD9577 Approved
0.76 Intermediate Similarity NPD322 Phase 1
0.7179 Intermediate Similarity NPD2220 Clinical (unspecified phase)
0.7143 Intermediate Similarity NPD7762 Phase 2
0.7143 Intermediate Similarity NPD7763 Phase 2
0.7059 Intermediate Similarity NPD2683 Discontinued
0.7042 Intermediate Similarity NPD1456 Approved
0.7021 Intermediate Similarity NPD8038 Phase 2
0.6923 Remote Similarity NPD4261 Phase 1
0.6712 Remote Similarity NPD9425 Approved
0.6625 Remote Similarity NPD620 Approved
0.6593 Remote Similarity NPD3177 Phase 3
0.6579 Remote Similarity NPD574 Approved
0.6556 Remote Similarity NPD3723 Clinical (unspecified phase)
0.6543 Remote Similarity NPD9649 Approved
0.6494 Remote Similarity NPD575 Clinical (unspecified phase)
0.6458 Remote Similarity NPD7841 Clinical (unspecified phase)
0.64 Remote Similarity NPD9433 Approved
0.6389 Remote Similarity NPD9204 Approved
0.6389 Remote Similarity NPD9205 Approved
0.6383 Remote Similarity NPD4780 Clinical (unspecified phase)
0.6337 Remote Similarity NPD6122 Discontinued
0.625 Remote Similarity NPD8847 Approved
0.625 Remote Similarity NPD8846 Approved
0.625 Remote Similarity NPD61 Approved
0.6173 Remote Similarity NPD1429 Clinical (unspecified phase)
0.6145 Remote Similarity NPD1439 Clinical (unspecified phase)
0.6136 Remote Similarity NPD4815 Discontinued
0.6125 Remote Similarity NPD348 Approved
0.6042 Remote Similarity NPD2682 Approved
0.5976 Remote Similarity NPD886 Clinical (unspecified phase)
0.5974 Remote Similarity NPD8865 Approved
0.5972 Remote Similarity NPD8950 Approved
0.5946 Remote Similarity NPD8785 Approved
0.593 Remote Similarity NPD366 Approved
0.5904 Remote Similarity NPD337 Discontinued
0.5904 Remote Similarity NPD4241 Registered
0.59 Remote Similarity NPD1784 Approved
0.5851 Remote Similarity NPD5791 Phase 2
0.5833 Remote Similarity NPD4242 Approved
0.5824 Remote Similarity NPD612 Discontinued
0.5814 Remote Similarity NPD6944 Clinical (unspecified phase)
0.573 Remote Similarity NPD9199 Approved
0.5728 Remote Similarity NPD6120 Clinical (unspecified phase)
0.5714 Remote Similarity NPD9105 Phase 2
0.5714 Remote Similarity NPD5792 Clinical (unspecified phase)
0.5714 Remote Similarity NPD9578 Clinical (unspecified phase)
0.5698 Remote Similarity NPD2262 Clinical (unspecified phase)
0.5686 Remote Similarity NPD3715 Approved
0.5686 Remote Similarity NPD3714 Approved
0.5686 Remote Similarity NPD3713 Approved
0.5667 Remote Similarity NPD3160 Suspended
0.5663 Remote Similarity NPD8952 Approved
0.5632 Remote Similarity NPD1147 Phase 2
0.5632 Remote Similarity NPD266 Phase 3
0.5632 Remote Similarity NPD265 Phase 3
0.5631 Remote Similarity NPD4825 Clinical (unspecified phase)
0.5612 Remote Similarity NPD1782 Approved
0.56 Remote Similarity NPD9441 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