Natural Product: NPC277021

Natural Product IDNPC277021
Common Name
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The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4-Methylesculetin
IUPAC Name 6,7-dihydroxy-4-methylchromen-2-one
Synonyms NSC-688807
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL313244
PubChem CID 5319502
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives
        • [CHEMONTID:0002908] Hydroxycoumarins
          • [CHEMONTID:0002643] 6,7-dihydroxycoumarins

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey KVOJTUXGYQVLAJ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C10H8O4/c1-5-2-10(13)14-9-4-8(12)7(11)3-6(5)9/h2-4,11-12H,1H3
SMILES O=c1cc(C)c2c(o1)cc(c(c2)O)O

  Calculated Properties

Physi-Chem Properties

MedChem Properties

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

ADMET: Distribution

ADMET: Metabolism

ADMET: Excretion

ADMET: Toxicity

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO12187 Convolvulus arvensis Species Convolvulaceae Eukaryota n.a. n.a. n.a. PMID[31181918]
NPO12187 Convolvulus arvensis Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12187 Convolvulus arvensis Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12187 Convolvulus arvensis Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12187 Convolvulus arvensis Species Convolvulaceae 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 Organism Name 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

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1551 Individual protein Sorbitol dehydrogenase Homo sapiens IC50 = 212000.0 nM PMID[20805028]
NPT149 Individual protein Endoplasmic reticulum-associated amyloid beta-peptide-binding protein Homo sapiens Potency = 15848.9 nM PubChem BioAssay data set
NPT151 Individual protein 15-hydroxyprostaglandin dehydrogenase [NAD+] Homo sapiens Potency = 15848.9 nM PubChem BioAssay data set
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens Potency = 15848.9 nM PubChem BioAssay data set
NPT72 Individual protein Solute carrier organic anion transporter family member 1B3 Homo sapiens Inhibition = 110.11 % PMID[23571415]
NPT940 Individual protein Serine/threonine-protein kinase mTOR Homo sapiens Kd = 1500000.0 nM PMID[10411471]
NPT41 Individual protein Aldose reductase Homo sapiens IC50 = 64400.0 nM PMID[20805028]
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 10000.0 nM PubChem BioAssay data set
NPT791 Individual protein Cruzipain Trypanosoma cruzi Potency = 3981.1 nM PubChem BioAssay data set
NPT94 Individual protein Aldehyde dehydrogenase 1A1 Homo sapiens Potency = 25118.9 nM PubChem BioAssay data set
NPT73 Individual protein Solute carrier organic anion transporter family member 1B1 Homo sapiens Inhibition = 121.75 % PMID[23571415]
NPT57 Individual protein Induced myeloid leukemia cell differentiation protein Mcl-1 Homo sapiens Ki = 1190.0 nM PMID[33218896]
NPT57 Individual protein Induced myeloid leukemia cell differentiation protein Mcl-1 Homo sapiens IC50 = 6280.0 nM PMID[33218896]
NPT967 Individual protein Xanthine dehydrogenase Homo sapiens IC50 = 246000.0 nM PMID[17316915]
NPT46 Individual protein Thyroid hormone receptor beta-1 Homo sapiens Potency = 70.8 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT466 Cell line U-937 Homo sapiens IC50 = 97400.0 nM PMID[26188907]
NPT466 Cell line U-937 Homo sapiens CC50 = 76000.0 nM PMID[26188907]
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 IC50 > 20000.0 nM DOI[10.6019/CHEMBL4651402]
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 IC50 > 19952.62 nM DOI[10.6019/CHEMBL4651402]
NPT2 Others Unspecified n.a. IC50 = 38300.0 nM PMID[20805028]
NPT2 Others Unspecified n.a. Ratio IC50 = 5.54 n.a. PMID[20805028]
NPT2 Others Unspecified n.a. Ratio IC50 = 1.68 n.a. PMID[20805028]
NPT2 Others Unspecified n.a. Potency = 31622.8 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. IC50 = 94250.0 nM PMID[21053896]
NPT2 Others Unspecified n.a. Potency n.a. 10000.0 nM PubChem BioAssay data set

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference
- Mus musculus LD50 = 3200.0 mg/kg ToxVal

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

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 toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC277021 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.6585 Remote Similarity NPC52247
0.587 Remote Similarity NPC608413
0.5476 Remote Similarity NPC137949
0.5227 Remote Similarity NPC601479

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC277021 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.6585 Remote Similarity NPD422 Phase 2

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by 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