Structure

Physi-Chem Properties

Molecular Weight:  223.07
Volume:  197.984
LogP:  -0.436
LogD:  -0.341
LogS:  -1.75
# Rotatable Bonds:  0
TPSA:  91.78
# H-Bond Aceptor:  8
# H-Bond Donor:  0
# Rings:  2
# Heavy Atoms:  8

MedChem Properties

QED Drug-Likeness Score:  0.502
Synthetic Accessibility Score:  2.862
Fsp3:  0.375
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:  -5.185
MDCK Permeability:  2.318648148502689e-05
Pgp-inhibitor:  0.863
Pgp-substrate:  0.261
Human Intestinal Absorption (HIA):  0.019
20% Bioavailability (F20%):  0.004
30% Bioavailability (F30%):  0.005

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.769
Plasma Protein Binding (PPB):  73.26979064941406%
Volume Distribution (VD):  1.464
Pgp-substrate:  35.66423797607422%

ADMET: Metabolism

CYP1A2-inhibitor:  0.043
CYP1A2-substrate:  0.984
CYP2C19-inhibitor:  0.014
CYP2C19-substrate:  0.296
CYP2C9-inhibitor:  0.002
CYP2C9-substrate:  0.405
CYP2D6-inhibitor:  0.003
CYP2D6-substrate:  0.094
CYP3A4-inhibitor:  0.003
CYP3A4-substrate:  0.855

ADMET: Excretion

Clearance (CL):  1.498
Half-life (T1/2):  0.666

ADMET: Toxicity

hERG Blockers:  0.004
Human Hepatotoxicity (H-HT):  0.215
Drug-inuced Liver Injury (DILI):  0.073
AMES Toxicity:  0.029
Rat Oral Acute Toxicity:  0.134
Maximum Recommended Daily Dose:  0.008
Skin Sensitization:  0.011
Carcinogencity:  0.011
Eye Corrosion:  0.003
Eye Irritation:  0.135
Respiratory Toxicity:  0.08

Download Data

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

  Natural Product: NPC270720

Natural Product ID:  NPC270720
Common Name*:   2,6,8-Trimethylpyrimido[5,4-E][1,2,4]Triazine-3,5,7-Trione
IUPAC Name:   2,6,8-trimethylpyrimido[5,4-e][1,2,4]triazine-3,5,7-trione
Synonyms:  
Standard InCHIKey:  NLCDJWLDGSBUOQ-UHFFFAOYSA-N
Standard InCHI:  InChI=1S/C8H9N5O3/c1-11-5-4(6(14)12(2)8(11)16)9-7(15)13(3)10-5/h1-3H3
SMILES:  O=c1nc2c(nn1C)n(C)c(=O)n(c2=O)C
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL446989
PubChem CID:   211238
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001346] Diazines
        • [CHEMONTID:0000075] Pyrimidines and pyrimidine derivatives
          • [CHEMONTID:0000291] Pyrimidones

*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
NPO22810 Streptomyces Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[11141106]
NPO22810 Streptomyces Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[11374972]
NPO22810 Streptomyces Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[15217282]
NPO22810 Streptomyces Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[15270566]

☑ 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
NPT1210 Individual Protein T-cell protein-tyrosine phosphatase Homo sapiens Activity = 34.0 % PMID[476800]
NPT6584 Individual Protein Serine/threonine-protein phosphatase Enterobacteria phage lambda Activity = 48.0 % PMID[476800]
NPT2 Others Unspecified Activity = 10.0 % PMID[476800]
NPT2 Others Unspecified Activity = 17.0 % PMID[476800]
NPT2 Others Unspecified Activity = 15.0 % PMID[476800]
NPT2 Others Unspecified Activity = 100.0 % PMID[476800]

☑ 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 NPC270720 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 NPC315551
0.6406 Remote Similarity NPC474992

  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 NPC270720 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
NPD

  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