Structure

Physi-Chem Properties

Molecular Weight:  200.12
Volume:  198.755
LogP:  0.244
LogD:  0.121
LogS:  -1.392
# Rotatable Bonds:  3
TPSA:  78.43
# H-Bond Aceptor:  5
# H-Bond Donor:  3
# Rings:  1
# Heavy Atoms:  5

MedChem Properties

QED Drug-Likeness Score:  0.547
Synthetic Accessibility Score:  3.2
Fsp3:  0.778
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:  -5.209
MDCK Permeability:  0.000963972881436348
Pgp-inhibitor:  0.0
Pgp-substrate:  0.05
Human Intestinal Absorption (HIA):  0.033
20% Bioavailability (F20%):  0.004
30% Bioavailability (F30%):  0.002

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.386
Plasma Protein Binding (PPB):  5.636911392211914%
Volume Distribution (VD):  0.534
Pgp-substrate:  84.19693756103516%

ADMET: Metabolism

CYP1A2-inhibitor:  0.019
CYP1A2-substrate:  0.068
CYP2C19-inhibitor:  0.03
CYP2C19-substrate:  0.098
CYP2C9-inhibitor:  0.015
CYP2C9-substrate:  0.542
CYP2D6-inhibitor:  0.002
CYP2D6-substrate:  0.141
CYP3A4-inhibitor:  0.017
CYP3A4-substrate:  0.113

ADMET: Excretion

Clearance (CL):  4.351
Half-life (T1/2):  0.7

ADMET: Toxicity

hERG Blockers:  0.008
Human Hepatotoxicity (H-HT):  0.162
Drug-inuced Liver Injury (DILI):  0.055
AMES Toxicity:  0.176
Rat Oral Acute Toxicity:  0.085
Maximum Recommended Daily Dose:  0.01
Skin Sensitization:  0.138
Carcinogencity:  0.069
Eye Corrosion:  0.003
Eye Irritation:  0.022
Respiratory Toxicity:  0.029

Download Data

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

  Natural Product: NPC137327

Natural Product ID:  NPC137327
Common Name*:   (3S,6S)-3-(Hydroxymethyl)-6-Isobutylpiperazine-2,5-Dione
IUPAC Name:   (3S,6S)-3-(hydroxymethyl)-6-(2-methylpropyl)piperazine-2,5-dione
Synonyms:  
Standard InCHIKey:  ANLAGVXTPHOKLD-BQBZGAKWSA-N
Standard InCHI:  InChI=1S/C9H16N2O3/c1-5(2)3-6-8(13)11-7(4-12)9(14)10-6/h5-7,12H,3-4H2,1-2H3,(H,10,14)(H,11,13)/t6-,7-/m0/s1
SMILES:  CC(C)C[C@H]1C(=N[C@@H](CO)C(=N1)O)O
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL1957405
PubChem CID:   57396597
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
NPO21891 Panax notoginseng Species Araliaceae Eukaryota Flower buds n.a. n.a. PMID[12880307]
NPO21891 Panax notoginseng Species Araliaceae Eukaryota Stems n.a. n.a. PMID[17663584]
NPO21891 Panax notoginseng Species Araliaceae Eukaryota Roots n.a. n.a. PMID[18186611]
NPO21891 Panax notoginseng Species Araliaceae Eukaryota Steamed Roots n.a. n.a. PMID[26200131]
NPO21891 Panax notoginseng Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21891 Panax notoginseng Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO21891 Panax notoginseng Species Araliaceae 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
NPT20529 NON-MOLECULAR NON-PROTEIN TARGET n.a. IC50 = 1000000.0 nM PMID[480205]
NPT20529 NON-MOLECULAR NON-PROTEIN TARGET n.a. Inhibition = 0.0 % PMID[480205]
NPT20529 NON-MOLECULAR NON-PROTEIN TARGET n.a. Inhibition = 95.2 % PMID[480205]

☑ 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 NPC137327 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
0.9167 High Similarity NPC87359
0.9167 High Similarity NPC180402
0.8036 Intermediate Similarity NPC472578
0.7885 Intermediate Similarity NPC80350
0.7083 Intermediate Similarity NPC25237
0.6984 Remote Similarity NPC41429
0.6818 Remote Similarity NPC472579
0.6724 Remote Similarity NPC270041
0.6721 Remote Similarity NPC321468
0.6721 Remote Similarity NPC327748
0.6667 Remote Similarity NPC322946
0.6667 Remote Similarity NPC195165
0.6667 Remote Similarity NPC317147
0.6613 Remote Similarity NPC329564
0.6613 Remote Similarity NPC327170
0.6545 Remote Similarity NPC319709
0.6545 Remote Similarity NPC289484
0.6508 Remote Similarity NPC314510
0.6491 Remote Similarity NPC224624
0.6471 Remote Similarity NPC478256
0.6452 Remote Similarity NPC316826
0.6452 Remote Similarity NPC317143
0.6438 Remote Similarity NPC312315
0.64 Remote Similarity NPC150560
0.6393 Remote Similarity NPC318260
0.6377 Remote Similarity NPC477200
0.6267 Remote Similarity NPC470783
0.6232 Remote Similarity NPC476285
0.6207 Remote Similarity NPC321394
0.6207 Remote Similarity NPC326283
0.6197 Remote Similarity NPC43219
0.6197 Remote Similarity NPC256312
0.6197 Remote Similarity NPC266888
0.6197 Remote Similarity NPC161774
0.6167 Remote Similarity NPC321118
0.6167 Remote Similarity NPC316889
0.6154 Remote Similarity NPC145627
0.6143 Remote Similarity NPC214532
0.6143 Remote Similarity NPC196007
0.6143 Remote Similarity NPC76297
0.6119 Remote Similarity NPC474402
0.6111 Remote Similarity NPC86064
0.6102 Remote Similarity NPC471131
0.6081 Remote Similarity NPC316242
0.6 Remote Similarity NPC315131
0.6 Remote Similarity NPC478017
0.6 Remote Similarity NPC476291
0.6 Remote Similarity NPC315535
0.5972 Remote Similarity NPC209156
0.5882 Remote Similarity NPC470108
0.5867 Remote Similarity NPC37681
0.5811 Remote Similarity NPC476130
0.5811 Remote Similarity NPC476324
0.5806 Remote Similarity NPC470666
0.5797 Remote Similarity NPC470109
0.5763 Remote Similarity NPC328378
0.5753 Remote Similarity NPC138435
0.5753 Remote Similarity NPC126186
0.5733 Remote Similarity NPC472594
0.5714 Remote Similarity NPC470110
0.5714 Remote Similarity NPC242930
0.5694 Remote Similarity NPC470781
0.5692 Remote Similarity NPC254541
0.5676 Remote Similarity NPC472595
0.5672 Remote Similarity NPC21848
0.5672 Remote Similarity NPC124849
0.5667 Remote Similarity NPC327239
0.5658 Remote Similarity NPC191774
0.5658 Remote Similarity NPC325902
0.5652 Remote Similarity NPC84182
0.5652 Remote Similarity NPC128005
0.5641 Remote Similarity NPC476302
0.5641 Remote Similarity NPC314466
0.5636 Remote Similarity NPC241279
0.5634 Remote Similarity NPC475808
0.5634 Remote Similarity NPC28348
0.5634 Remote Similarity NPC474298
0.5634 Remote Similarity NPC473985
0.5634 Remote Similarity NPC474299
0.5616 Remote Similarity NPC141325
0.5606 Remote Similarity NPC471129

  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 NPC137327 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
0.8039 Intermediate Similarity NPD362 Phase 1
0.717 Intermediate Similarity NPD379 Clinical (unspecified phase)
0.6984 Remote Similarity NPD1831 Phase 3
0.6897 Remote Similarity NPD1830 Clinical (unspecified phase)
0.6786 Remote Similarity NPD325 Approved
0.6769 Remote Similarity NPD2263 Discontinued
0.6765 Remote Similarity NPD3187 Discontinued
0.6667 Remote Similarity NPD1152 Phase 2
0.6667 Remote Similarity NPD9441 Phase 2
0.6607 Remote Similarity NPD323 Approved
0.6552 Remote Similarity NPD609 Approved
0.6552 Remote Similarity NPD611 Approved
0.6545 Remote Similarity NPD3211 Approved
0.6491 Remote Similarity NPD324 Approved
0.6491 Remote Similarity NPD903 Approved
0.6441 Remote Similarity NPD608 Approved
0.6441 Remote Similarity NPD610 Approved
0.6441 Remote Similarity NPD607 Approved
0.6441 Remote Similarity NPD606 Approved
0.6324 Remote Similarity NPD3724 Clinical (unspecified phase)
0.6296 Remote Similarity NPD9400 Approved
0.6296 Remote Similarity NPD9399 Approved
0.6207 Remote Similarity NPD9678 Approved
0.6207 Remote Similarity NPD9677 Phase 3
0.619 Remote Similarity NPD354 Approved
0.6 Remote Similarity NPD7918 Clinical (unspecified phase)
0.6 Remote Similarity NPD7917 Clinical (unspecified phase)
0.5946 Remote Similarity NPD2689 Clinical (unspecified phase)
0.5938 Remote Similarity NPD570 Approved
0.5873 Remote Similarity NPD9647 Approved
0.5849 Remote Similarity NPD9453 Phase 3
0.5846 Remote Similarity NPD571 Approved
0.5811 Remote Similarity NPD1453 Phase 1
0.5735 Remote Similarity NPD277 Approved
0.5672 Remote Similarity NPD835 Approved
0.5672 Remote Similarity NPD834 Approved
0.5658 Remote Similarity NPD4278 Clinical (unspecified phase)
0.5625 Remote Similarity NPD273 Approved
0.5616 Remote Similarity NPD1147 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