Structure

Physi-Chem Properties

Molecular Weight:  210.14
Volume:  216.0
LogP:  1.051
LogD:  0.86
LogS:  -1.519
# Rotatable Bonds:  2
TPSA:  49.41
# H-Bond Aceptor:  4
# H-Bond Donor:  1
# Rings:  2
# Heavy Atoms:  4

MedChem Properties

QED Drug-Likeness Score:  0.722
Synthetic Accessibility Score:  3.282
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:  -4.579
MDCK Permeability:  9.689862963568885e-06
Pgp-inhibitor:  0.002
Pgp-substrate:  0.01
Human Intestinal Absorption (HIA):  0.012
20% Bioavailability (F20%):  0.006
30% Bioavailability (F30%):  0.04

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.935
Plasma Protein Binding (PPB):  47.313079833984375%
Volume Distribution (VD):  0.77
Pgp-substrate:  54.22022247314453%

ADMET: Metabolism

CYP1A2-inhibitor:  0.017
CYP1A2-substrate:  0.208
CYP2C19-inhibitor:  0.059
CYP2C19-substrate:  0.821
CYP2C9-inhibitor:  0.02
CYP2C9-substrate:  0.38
CYP2D6-inhibitor:  0.013
CYP2D6-substrate:  0.223
CYP3A4-inhibitor:  0.045
CYP3A4-substrate:  0.279

ADMET: Excretion

Clearance (CL):  6.846
Half-life (T1/2):  0.801

ADMET: Toxicity

hERG Blockers:  0.006
Human Hepatotoxicity (H-HT):  0.529
Drug-inuced Liver Injury (DILI):  0.114
AMES Toxicity:  0.011
Rat Oral Acute Toxicity:  0.328
Maximum Recommended Daily Dose:  0.078
Skin Sensitization:  0.089
Carcinogencity:  0.03
Eye Corrosion:  0.003
Eye Irritation:  0.028
Respiratory Toxicity:  0.052

Download Data

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

  Natural Product: NPC209156

Natural Product ID:  NPC209156
Common Name*:   Cyclo(D)-Pro-(D)-Ile
IUPAC Name:   (3R,8aR)-3-[(2R)-butan-2-yl]-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
Synonyms:  
Standard InCHIKey:  ZDACRNZBFJOLTC-IWSPIJDZSA-N
Standard InCHI:  InChI=1S/C11H18N2O2/c1-3-7(2)9-11(15)13-6-4-5-8(13)10(14)12-9/h7-9H,3-6H2,1-2H3,(H,12,14)/t7-,8-,9-/m1/s1
SMILES:  CC[C@@H](C)[C@@H]1C(=O)N2CCC[C@@H]2C(=N1)O
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL513788
PubChem CID:   44566897
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
NPO15584 Pecten maximus Species Pectinidae Eukaryota n.a. n.a. n.a. PMID[14575426]
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. n.a. n.a. PMID[18071251]
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. faeces n.a. PMID[18323202]
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22874 Bombyx mori Species Bombycidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15584 Pecten maximus Species Pectinidae 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
NPT1311 Organism Listonella anguillarum Listonella anguillarum MIC = 0.05 ug.mL-1 PMID[541477]

☑ 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 NPC209156 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
0.9706 High Similarity NPC256312
0.9706 High Similarity NPC266888
0.9706 High Similarity NPC161774
0.9701 High Similarity NPC196007
0.9701 High Similarity NPC76297
0.9701 High Similarity NPC214532
0.9041 High Similarity NPC312315
0.8955 High Similarity NPC128005
0.8955 High Similarity NPC84182
0.88 High Similarity NPC470783
0.8507 High Similarity NPC243964
0.8108 Intermediate Similarity NPC126186
0.8082 Intermediate Similarity NPC470781
0.7949 Intermediate Similarity NPC476156
0.7949 Intermediate Similarity NPC476137
0.7949 Intermediate Similarity NPC476117
0.7949 Intermediate Similarity NPC476243
0.7848 Intermediate Similarity NPC476302
0.7821 Intermediate Similarity NPC31756
0.7662 Intermediate Similarity NPC470782
0.7564 Intermediate Similarity NPC59867
0.7532 Intermediate Similarity NPC327272
0.7273 Intermediate Similarity NPC471098
0.7273 Intermediate Similarity NPC173763
0.7273 Intermediate Similarity NPC62263
0.7241 Intermediate Similarity NPC474593
0.7241 Intermediate Similarity NPC475801
0.7195 Intermediate Similarity NPC475542
0.7176 Intermediate Similarity NPC477539
0.7159 Intermediate Similarity NPC474576
0.7108 Intermediate Similarity NPC84128
0.7108 Intermediate Similarity NPC53858
0.7105 Intermediate Similarity NPC322274
0.6957 Remote Similarity NPC473597
0.6941 Remote Similarity NPC472351
0.6933 Remote Similarity NPC287693
0.6905 Remote Similarity NPC184473
0.6778 Remote Similarity NPC477538
0.6774 Remote Similarity NPC47076
0.6774 Remote Similarity NPC134504
0.675 Remote Similarity NPC320221
0.6706 Remote Similarity NPC6902
0.6632 Remote Similarity NPC475440
0.6629 Remote Similarity NPC473495
0.6622 Remote Similarity NPC314510
0.6598 Remote Similarity NPC475149
0.6598 Remote Similarity NPC471097
0.6588 Remote Similarity NPC23984
0.6559 Remote Similarity NPC280066
0.6556 Remote Similarity NPC275715
0.6512 Remote Similarity NPC284456
0.6489 Remote Similarity NPC117829
0.6465 Remote Similarity NPC323720
0.6458 Remote Similarity NPC220234
0.6458 Remote Similarity NPC475758
0.6452 Remote Similarity NPC301010
0.6447 Remote Similarity NPC57420
0.6437 Remote Similarity NPC235078
0.64 Remote Similarity NPC241394
0.64 Remote Similarity NPC475637
0.6392 Remote Similarity NPC475791
0.6392 Remote Similarity NPC13175
0.6351 Remote Similarity NPC317143
0.6351 Remote Similarity NPC316826
0.6324 Remote Similarity NPC87359
0.6324 Remote Similarity NPC180402
0.6316 Remote Similarity NPC105297
0.6301 Remote Similarity NPC318260
0.63 Remote Similarity NPC128303
0.6267 Remote Similarity NPC329564
0.6267 Remote Similarity NPC327170
0.6263 Remote Similarity NPC5864
0.6263 Remote Similarity NPC301148
0.6263 Remote Similarity NPC124554
0.622 Remote Similarity NPC29326
0.62 Remote Similarity NPC476877
0.6154 Remote Similarity NPC128559
0.6139 Remote Similarity NPC124549
0.6133 Remote Similarity NPC327748
0.6133 Remote Similarity NPC321468
0.6122 Remote Similarity NPC475188
0.6117 Remote Similarity NPC207820
0.6081 Remote Similarity NPC317147
0.6078 Remote Similarity NPC476876
0.6056 Remote Similarity NPC471131
0.6056 Remote Similarity NPC322946
0.6047 Remote Similarity NPC325902
0.604 Remote Similarity NPC198344
0.6022 Remote Similarity NPC155230
0.6022 Remote Similarity NPC322966
0.5981 Remote Similarity NPC63191
0.5981 Remote Similarity NPC471202
0.5972 Remote Similarity NPC8488
0.5972 Remote Similarity NPC274499
0.5972 Remote Similarity NPC137327
0.5972 Remote Similarity NPC333075
0.5962 Remote Similarity NPC67009
0.5962 Remote Similarity NPC171734
0.5926 Remote Similarity NPC250953
0.5926 Remote Similarity NPC306696
0.5909 Remote Similarity NPC315276
0.5909 Remote Similarity NPC285926
0.5909 Remote Similarity NPC14672
0.5895 Remote Similarity NPC476019
0.5833 Remote Similarity NPC315237
0.5794 Remote Similarity NPC476875
0.5778 Remote Similarity NPC246005
0.5758 Remote Similarity NPC144780
0.5752 Remote Similarity NPC315188
0.575 Remote Similarity NPC160661
0.5747 Remote Similarity NPC329077
0.5745 Remote Similarity NPC324506
0.5727 Remote Similarity NPC296043
0.5714 Remote Similarity NPC34838
0.5714 Remote Similarity NPC292299
0.5714 Remote Similarity NPC254541
0.5714 Remote Similarity NPC469899
0.5702 Remote Similarity NPC200964
0.5676 Remote Similarity NPC321118
0.5676 Remote Similarity NPC316889
0.5676 Remote Similarity NPC329216
0.5663 Remote Similarity NPC15864
0.566 Remote Similarity NPC296143
0.5657 Remote Similarity NPC469739
0.5647 Remote Similarity NPC315897
0.5641 Remote Similarity NPC263207
0.5614 Remote Similarity NPC160688
0.5612 Remote Similarity NPC38172

  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 NPC209156 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
0.8684 High Similarity NPD2683 Discontinued
0.8077 Intermediate Similarity NPD7763 Phase 2
0.8077 Intermediate Similarity NPD7762 Phase 2
0.7808 Intermediate Similarity NPD620 Approved
0.7671 Intermediate Similarity NPD322 Phase 1
0.759 Intermediate Similarity NPD7759 Phase 2
0.759 Intermediate Similarity NPD7760 Phase 2
0.759 Intermediate Similarity NPD3723 Clinical (unspecified phase)
0.7531 Intermediate Similarity NPD1125 Discovery
0.7353 Intermediate Similarity NPD1456 Approved
0.7 Intermediate Similarity NPD9425 Approved
0.6882 Remote Similarity NPD8038 Phase 2
0.6848 Remote Similarity NPD7841 Clinical (unspecified phase)
0.6818 Remote Similarity NPD3177 Phase 3
0.6795 Remote Similarity NPD9649 Approved
0.6795 Remote Similarity NPD1439 Clinical (unspecified phase)
0.6744 Remote Similarity NPD9577 Approved
0.6593 Remote Similarity NPD4780 Clinical (unspecified phase)
0.6593 Remote Similarity NPD4261 Phase 1
0.6593 Remote Similarity NPD2682 Approved
0.6582 Remote Similarity NPD2220 Clinical (unspecified phase)
0.6548 Remote Similarity NPD4815 Discontinued
0.6531 Remote Similarity NPD6122 Discontinued
0.642 Remote Similarity NPD266 Phase 3
0.642 Remote Similarity NPD265 Phase 3
0.6404 Remote Similarity NPD5791 Phase 2
0.6351 Remote Similarity NPD9671 Phase 2
0.6351 Remote Similarity NPD9670 Phase 2
0.6337 Remote Similarity NPD6937 Approved
0.6324 Remote Similarity NPD362 Phase 1
0.6301 Remote Similarity NPD581 Approved
0.6301 Remote Similarity NPD583 Approved
0.6301 Remote Similarity NPD843 Clinical (unspecified phase)
0.6301 Remote Similarity NPD584 Approved
0.625 Remote Similarity NPD1784 Approved
0.6237 Remote Similarity NPD5792 Clinical (unspecified phase)
0.6203 Remote Similarity NPD9665 Clinical (unspecified phase)
0.6203 Remote Similarity NPD9666 Clinical (unspecified phase)
0.6186 Remote Similarity NPD3713 Approved
0.6186 Remote Similarity NPD3714 Approved
0.6186 Remote Similarity NPD3715 Approved
0.6104 Remote Similarity NPD9625 Approved
0.6056 Remote Similarity NPD9441 Phase 2
0.6023 Remote Similarity NPD612 Discontinued
0.6 Remote Similarity NPD8950 Approved
0.6 Remote Similarity NPD605 Clinical (unspecified phase)
0.6 Remote Similarity NPD6699 Clinical (unspecified phase)
0.5978 Remote Similarity NPD3176 Clinical (unspecified phase)
0.596 Remote Similarity NPD4825 Clinical (unspecified phase)
0.593 Remote Similarity NPD9199 Approved
0.5921 Remote Similarity NPD354 Approved
0.59 Remote Similarity NPD5359 Clinical (unspecified phase)
0.5824 Remote Similarity NPD3733 Clinical (unspecified phase)
0.5789 Remote Similarity NPD1782 Approved
0.5789 Remote Similarity NPD8784 Clinical (unspecified phase)
0.5745 Remote Similarity NPD868 Phase 3
0.5745 Remote Similarity NPD867 Phase 3
0.5743 Remote Similarity NPD6120 Clinical (unspecified phase)
0.5733 Remote Similarity NPD9105 Phase 2
0.573 Remote Similarity NPD9578 Clinical (unspecified phase)
0.5698 Remote Similarity NPD9198 Approved
0.5698 Remote Similarity NPD9367 Discontinued
0.5658 Remote Similarity NPD9647 Approved
0.5647 Remote Similarity NPD1825 Clinical (unspecified phase)
0.5644 Remote Similarity NPD3103 Approved
0.5644 Remote Similarity NPD3104 Approved
0.5644 Remote Similarity NPD3102 Approved
0.5644 Remote Similarity NPD3101 Approved
0.5618 Remote Similarity NPD617 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