Natural Product: NPC165257

Natural Product IDNPC165257
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2-Methoxyjuglone
IUPAC Name 5-hydroxy-2-methoxynaphthalene-1,4-dione
Synonyms 2-Methoxyjuglone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL480099
PubChem CID 10104346
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000023] Naphthalenes
        • [CHEMONTID:0000153] Naphthoquinones

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 GATGZQSBJAZYRT-UHFFFAOYSA-N
Standard InCHI InChI=1S/C11H8O4/c1-15-9-5-8(13)10-6(11(9)14)3-2-4-7(10)12/h2-5,12H,1H3
SMILES COC1=CC(=O)c2c(cccc2O)C1=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   204.04 Volume:   201.042
?
Van der Waals volume.
Dense:   1.015 LogP:   1.495
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.688
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.123
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   13.0
TPSA:   63.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.748 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.305 Fsp3:   0.091
MCE-18:   24.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   0.116 Fluc inhibitor:   0.678
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.822
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.567
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.786 Promiscuous compounds:   0.266

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.698 MDCK Permeability:   -4.646
Pgp-inhibitor:   0.048 Pgp-substrate:   0.004
PAMPA:   0.777
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.686
20% Bioavailability (F20%):   0.018 30% Bioavailability (F30%):   0.202
50% Bioavailability (F50%):   0.724

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.416
Plasma Protein Binding (PPB):   94.812% Volume Distribution (VD):   -0.119
Fu: 5.117%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.012
BSEP inhibitor:   0.149

ADMET: Metabolism

CYP1A2-inhibitor:   0.991 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.013 CYP2C19-substrate:   0.628
CYP2C9-inhibitor:   0.617 CYP2C9-substrate:   0.888
CYP2D6-inhibitor:   0.359 CYP2D6-substrate:   0.558
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.988
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.997
HLM stability:   0.867
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  5.531 Half-life (T1/2):  1.183

ADMET: Toxicity

hERG Blockers:  0.047 hERG Blockers (10um):  0.458
Human Hepatotoxicity (H-HT):  0.617 Drug-induced Liver Injury (DILI):  0.752
AMES Toxicity:  0.849 Rat Oral Acute Toxicity:  0.494
Maximum Recommended Daily Dose:  0.543 Skin Sensitization:  0.924
Carcinogencity:  0.766 Eye Corrosion:  0.18
Eye Irritation:  0.993 Respiratory Toxicity:  0.819
Drug-induced Neurotoxicity:  0.371 Ototoxicity:  0.188
Hematotoxicity:  0.614 Drug-induced Nephrotoxicity:  0.371
Genotoxicity:  0.838 RPMI-8226 Immunitoxicity:  0.155
A549 Cytotoxicity:  0.345 Hek293 Cytotoxicity:  0.386
BCF:   2.222
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   4.735
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.377
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.946
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO26892 Juglans mandshurica Species Juglandaceae Eukaryota roots n.a. n.a. PMID[12444709]
NPO18674 Juglans regia Species Juglandaceae Eukaryota n.a. root n.a. PMID[14727919]
NPO18674 Juglans regia Species Juglandaceae Eukaryota n.a. leaf n.a. PMID[14727919]
NPO18674 Juglans regia Species Juglandaceae Eukaryota n.a. xylem n.a. PMID[14727919]
NPO18674 Juglans regia Species Juglandaceae Eukaryota n.a. bark n.a. PMID[14727919]
NPO18674 Juglans regia Species Juglandaceae Eukaryota n.a. pericarp n.a. PMID[18496782]
NPO18674 Juglans regia Species Juglandaceae Eukaryota n.a. n.a. n.a. PMID[25466114]
NPO18674 Juglans regia Species Juglandaceae Eukaryota Flowers n.a. n.a. PMID[28737396]
NPO40992 Penicillium thomii YPGA3 Strain Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[32902982]
NPO18674 Juglans regia Species Juglandaceae Eukaryota n.a. n.a. n.a. PMID[36431782]
NPO18674 Juglans regia Species Juglandaceae Eukaryota n.a. n.a. n.a. PMID[37570937]
NPO26892 Juglans mandshurica Species Juglandaceae Eukaryota Roots n.a. n.a. PMID[9599266]
NPO18674 Juglans regia Species Juglandaceae Eukaryota n.a. leaf n.a. Database[Article]
NPO18674 Juglans regia Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26892 Juglans mandshurica Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20411 Engelhardia roxburghiana Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO40992 Penicillium thomii YPGA3 Strain Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18674 Juglans regia Species Juglandaceae Eukaryota Embryo n.a. n.a. Database[FooDB]
NPO18674 Juglans regia Species Juglandaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO18674 Juglans regia Species Juglandaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO18674 Juglans regia Species Juglandaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO18674 Juglans regia Species Juglandaceae Eukaryota Stem Bark n.a. n.a. Database[FooDB]
NPO18674 Juglans regia Species Juglandaceae Eukaryota Testa n.a. n.a. Database[FooDB]
NPO18674 Juglans regia Species Juglandaceae Eukaryota n.a. n.a. Database[FooDB]
NPO18674 Juglans regia Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26892 Juglans mandshurica Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20411 Engelhardia roxburghiana Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18674 Juglans regia Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18674 Juglans regia Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18674 Juglans regia Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20411 Engelhardia roxburghiana Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26892 Juglans mandshurica Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18674 Juglans regia Species Juglandaceae 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT139 Cell line HT-29 Homo sapiens IC50 = 2.63 ug.mL-1 PMID[9599266]
NPT81 Cell line A549 Homo sapiens IC50 = 0.08 ug.mL-1 PMID[9599266]
NPT1357 Cell line H22 Mus musculus Activity = 67.0 % PMID[23597099]
NPT1357 Cell line H22 Mus musculus Activity = 56.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 0.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 46.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 54.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 33.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 2.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 52.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 18.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 66.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 32.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 6.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 1.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 64.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 35.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 4.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 49.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 50.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 59.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 41.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 7.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 61.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 37.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 62.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 38.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 34.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens Activity = 5.0 % PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens IC50 = 2.7 ug.mL-1 PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens IC50 = 3.7 ug.mL-1 PMID[23597099]
NPT65 Cell line HepG2 Homo sapiens IC50 = 3.8 ug.mL-1 PMID[23597099]
NPT165 Cell line HeLa Homo sapiens IC50 = 1180.0 nM PMID[24631733]
NPT165 Cell line HeLa Homo sapiens IC50 = 1290.0 nM PMID[24631733]
NPT165 Cell line HeLa Homo sapiens Ratio = 2.19 n.a. PMID[24631733]
NPT407 Cell line COLO 205 Homo sapiens IC50 = 2300.0 nM PMID[29735338]
NPT396 Cell line T47D Homo sapiens IC50 = 2000.0 nM PMID[29735338]
NPT111 Cell line K562 Homo sapiens IC50 = 1400.0 nM PMID[29735338]
NPT113 Cell line RAW264.7 Mus musculus Inhibition < 30.0 % PMID[32902982]
NPT784 Cell line MDA-MB-468 Homo sapiens IC50 = 4900.0 nM PMID[32902982]
NPT83 Cell line MCF7 Homo sapiens IC50 = 11000.0 nM PMID[32902982]
NPT83 Cell line MCF7 Homo sapiens Activity > 50.0 % PMID[32902982]
NPT784 Cell line MDA-MB-468 Homo sapiens Activity > 50.0 % PMID[32902982]
NPT165 Cell line HeLa Homo sapiens INCC50 = 0.59 uM PMID[24631733]
NPT23295 Cell line LNCaP C4-2B Homo sapiens IC50 = 13000.0 nM PMID[32902982]
NPT23295 Cell line LNCaP C4-2B Homo sapiens IC50 = 6400.0 nM PMID[32902982]
NPT23295 Cell line LNCaP C4-2B Homo sapiens Activity > 50.0 % PMID[32902982]
NPT790 Organism Mycobacterium tuberculosis H37Rv Mycobacterium tuberculosis H37Rv MIC = 30.0 ug.mL-1 PMID[22280816]

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

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 NPC165257 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
0.7949 Intermediate Similarity NPC51037
0.6279 Remote Similarity NPC309430
0.5909 Remote Similarity NPC487779
0.5897 Remote Similarity NPC112552
0.5532 Remote Similarity NPC603864
0.55 Remote Similarity NPC108288
0.5435 Remote Similarity NPC237225
0.5319 Remote Similarity NPC254603
0.5227 Remote Similarity NPC285829
0.5217 Remote Similarity NPC198305
0.5111 Remote Similarity NPC600470

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC165257 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
0.55 Remote Similarity NPD405 Clinical (unspecified phase)

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