Structure

Physi-Chem Properties

Molecular Weight:  199.06
Volume:  178.677
LogP:  -3.051
LogD:  -1.563
LogS:  -1.71
# Rotatable Bonds:  3
TPSA:  118.18
# H-Bond Aceptor:  7
# H-Bond Donor:  4
# Rings:  1
# Heavy Atoms:  7

MedChem Properties

QED Drug-Likeness Score:  0.517
Synthetic Accessibility Score:  2.93
Fsp3:  0.286
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:  -6.13
MDCK Permeability:  0.006350808776915073
Pgp-inhibitor:  0.0
Pgp-substrate:  0.082
Human Intestinal Absorption (HIA):  0.197
20% Bioavailability (F20%):  0.004
30% Bioavailability (F30%):  0.005

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.799
Plasma Protein Binding (PPB):  8.150135040283203%
Volume Distribution (VD):  0.255
Pgp-substrate:  86.42902374267578%

ADMET: Metabolism

CYP1A2-inhibitor:  0.005
CYP1A2-substrate:  0.064
CYP2C19-inhibitor:  0.048
CYP2C19-substrate:  0.037
CYP2C9-inhibitor:  0.029
CYP2C9-substrate:  0.102
CYP2D6-inhibitor:  0.245
CYP2D6-substrate:  0.124
CYP3A4-inhibitor:  0.005
CYP3A4-substrate:  0.014

ADMET: Excretion

Clearance (CL):  5.269
Half-life (T1/2):  0.822

ADMET: Toxicity

hERG Blockers:  0.011
Human Hepatotoxicity (H-HT):  0.393
Drug-inuced Liver Injury (DILI):  0.945
AMES Toxicity:  0.053
Rat Oral Acute Toxicity:  0.015
Maximum Recommended Daily Dose:  0.005
Skin Sensitization:  0.051
Carcinogencity:  0.082
Eye Corrosion:  0.003
Eye Irritation:  0.024
Respiratory Toxicity:  0.04

Download Data

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

  Natural Product: NPC192521

Natural Product ID:  NPC192521
Common Name*:   (S)-Willardiine
IUPAC Name:   (2S)-2-azaniumyl-3-(2,4-dioxopyrimidin-1-yl)propanoate
Synonyms:  
Standard InCHIKey:  FACUYWPMDKTVFU-BYPYZUCNSA-N
Standard InCHI:  InChI=1S/C7H9N3O4/c8-4(6(12)13)3-10-2-1-5(11)9-7(10)14/h1-2,4H,3,8H2,(H,12,13)(H,9,11,14)/t4-/m0/s1
SMILES:  c1cn(C[C@@H](C(=O)O)N)c(=O)nc1O
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL122005
PubChem CID:   25200769
440053
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
              • [CHEMONTID:0002404] Alpha amino acids
                • [CHEMONTID:0004146] L-alpha-amino acids

*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
NPO27633 Coriaria ruscifolia Species Coriariaceae Eukaryota n.a. fruit n.a. PMID[11429254]
NPO4682 Lindera aggregata Species Lauraceae Eukaryota n.a. leaf n.a. PMID[17999353]
NPO4682 Lindera aggregata Species Lauraceae Eukaryota Roots; Tubers n.a. n.a. PMID[19639966]
NPO27399 Mycale hentscheli Species Mycalidae Eukaryota n.a. n.a. n.a. PMID[30188708]
NPO27104 0thopanax davidii n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO27653 Lablab niger Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4682 Lindera aggregata Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27104 0thopanax davidii n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO27653 Lablab niger Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27104 0thopanax davidii n.a. n.a. n.a. n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4682 Lindera aggregata Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO27936 Arachniodes sporadosora Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26334 Pleurobranchaea meckelii Species Pleurobranchidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27667 Scolopia spinosa Species Salicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27399 Mycale hentscheli Species Mycalidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27104 0thopanax davidii n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO4682 Lindera aggregata Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27542 Parmelia glabrans Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27716 Salacia campestris Species Sertulariidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26638 Helwingia chinensis Species Helwingiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27633 Coriaria ruscifolia Species Coriariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27653 Lablab niger Species Fabaceae 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
NPT3741 Individual Protein Glutamate receptor ionotropic, AMPA 1 Homo sapiens Ki = 386.0 nM PMID[471019]
NPT3742 Individual Protein Glutamate receptor ionotropic, AMPA 2 Homo sapiens Ki = 898.0 nM PMID[471019]
NPT3743 Individual Protein Glutamate receptor ionotropic, AMPA 4 Homo sapiens Ki = 8850.0 nM PMID[471019]
NPT3745 Individual Protein Glutamate receptor ionotropic kainate 5 Homo sapiens Ki = 28900.0 nM PMID[471019]
NPT4576 Individual Protein Glutamate carboxypeptidase II Homo sapiens IC50 = 67000.0 nM PMID[471020]
NPT3750 Individual Protein Glutamate receptor ionotropic, AMPA 1 Rattus norvegicus EC50 = 11500.0 nM PMID[471021]
NPT5 Individual Protein Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Homo sapiens Potency n.a. 1500.3 nM PMID[471023]
NPT71 Cell Line HEK293 Homo sapiens Potency n.a. 163.5 nM PMID[471023]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae Potency = 4610.9 nM PMID[471023]
NPT888 Individual Protein 78 kDa glucose-regulated protein Homo sapiens Potency n.a. 18492.7 nM PMID[471023]

☑ 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 NPC192521 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
0.6962 Remote Similarity NPC126293
0.5946 Remote Similarity NPC10915
0.5897 Remote Similarity NPC273037
0.5733 Remote Similarity NPC327831
0.5714 Remote Similarity NPC297220
0.5652 Remote Similarity NPC106780
0.5638 Remote Similarity NPC89051
0.5638 Remote Similarity NPC43246
0.561 Remote Similarity NPC193559

  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 NPC192521 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
0.6962 Remote Similarity NPD9355 Approved
0.6962 Remote Similarity NPD9354 Clinical (unspecified phase)
0.5952 Remote Similarity NPD9432 Discontinued
0.5865 Remote Similarity NPD1385 Discontinued
0.5773 Remote Similarity NPD1686 Approved
0.5729 Remote Similarity NPD9565 Discontinued
0.5641 Remote Similarity NPD9368 Phase 2
0.5638 Remote Similarity NPD9581 Clinical (unspecified phase)
0.5638 Remote Similarity NPD9580 Clinical (unspecified phase)

  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