Natural Product: NPC182646

Natural Product IDNPC182646
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Sid22411775
IUPAC Name 5-methoxy-2-methylnaphthalene-1,4-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1531003
PubChem CID 185478
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 ITNOIFSYUBMQKB-UHFFFAOYSA-N
Standard InCHI InChI=1S/C12H10O3/c1-7-6-9(13)11-8(12(7)14)4-3-5-10(11)15-2/h3-6H,1-2H3
SMILES CC1=CC(=O)c2c(cccc2OC)C1=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   202.06 Volume:   209.547
?
Van der Waals volume.
Dense:   0.964 LogP:   1.899
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.182
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.926
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   13.0
TPSA:   43.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.699 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.122 Fsp3:   0.167
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:   0.042 Fluc inhibitor:   0.649
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.684
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.326
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.794 Promiscuous compounds:   0.348

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.677 MDCK Permeability:   -4.556
Pgp-inhibitor:   0.54 Pgp-substrate:   0.014
PAMPA:   0.751
?
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):   0.86
20% Bioavailability (F20%):   0.053 30% Bioavailability (F30%):   0.661
50% Bioavailability (F50%):   0.738

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.004 MRP1:   0.843
Plasma Protein Binding (PPB):   92.567% Volume Distribution (VD):   0.03
Fu: 6.146%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.988
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.002
BSEP inhibitor:   0.931

ADMET: Metabolism

CYP1A2-inhibitor:   0.992 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.01 CYP2C19-substrate:   0.892
CYP2C9-inhibitor:   0.107 CYP2C9-substrate:   0.988
CYP2D6-inhibitor:   0.008 CYP2D6-substrate:   0.438
CYP3A4-inhibitor:   0.008 CYP3A4-substrate:   0.956
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.765
HLM stability:   0.295
?
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):  8.608 Half-life (T1/2):  1.068

ADMET: Toxicity

hERG Blockers:  0.109 hERG Blockers (10um):  0.558
Human Hepatotoxicity (H-HT):  0.752 Drug-induced Liver Injury (DILI):  0.71
AMES Toxicity:  0.786 Rat Oral Acute Toxicity:  0.611
Maximum Recommended Daily Dose:  0.616 Skin Sensitization:  0.942
Carcinogencity:  0.848 Eye Corrosion:  0.903
Eye Irritation:  0.997 Respiratory Toxicity:  0.866
Drug-induced Neurotoxicity:  0.719 Ototoxicity:  0.213
Hematotoxicity:  0.702 Drug-induced Nephrotoxicity:  0.282
Genotoxicity:  0.492 RPMI-8226 Immunitoxicity:  0.078
A549 Cytotoxicity:  0.09 Hek293 Cytotoxicity:  0.433
BCF:   1.74
?
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:   4.469
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.926
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.321
?
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
NPO6969 Triphyophyllum peltatum Species Dioncophyllaceae Eukaryota n.a. root n.a. DOI[10.1007/s004360050318]
NPO6969 Triphyophyllum peltatum Species Dioncophyllaceae Eukaryota n.a. stem n.a. DOI[10.1007/s004360050318]
NPO6969 Triphyophyllum peltatum Species Dioncophyllaceae Eukaryota n.a. n.a. n.a. PMID[22019229]
NPO32707 burman diospyros burmanica Species n.a. n.a. n.a. n.a. n.a. PMID[22858297]
NPO6969 Triphyophyllum peltatum Species Dioncophyllaceae Eukaryota n.a. stem n.a. PMID[9371362]
NPO6969 Triphyophyllum peltatum Species Dioncophyllaceae Eukaryota n.a. root n.a. PMID[9371362]
NPO6969 Triphyophyllum peltatum Species Dioncophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6969 Triphyophyllum peltatum Species Dioncophyllaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6969 Triphyophyllum peltatum Species Dioncophyllaceae 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
NPT1197 Individual protein Huntingtin Homo sapiens Potency = 14125.4 nM PMID[23795939]
NPT3 Individual protein Thioredoxin glutathione reductase Schistosoma mansoni Potency = 39810.7 nM PMID[15387673]
NPT1282 Individual protein Microphthalmia-associated transcription factor Homo sapiens AC50 = 7828.0 nM PMID[17470656]
NPT1861 Individual protein Mitochondrial import inner membrane translocase subunit TIM10 Saccharomyces cerevisiae S288c IC50 = 13200.0 nM PMID[16562846]
NPT1282 Individual protein Microphthalmia-associated transcription factor Homo sapiens AC50 = 18804.0 nM PubChem BioAssay data set
NPT198 Individual protein Vitamin D receptor Homo sapiens Potency n.a. 39810.7 nM PMID[26290401]
NPT154 Individual protein Mothers against decapentaplegic homolog 3 Homo sapiens Potency n.a. 35481.3 nM PMID[21612217]
NPT2971 Individual protein DNA dC->dU-editing enzyme APOBEC-3F Homo sapiens Potency n.a. 11220.2 nM PMID[25871261]
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 23109.3 nM PMID[26331426]
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 20596.2 nM PMID[9677276]
NPT101 Individual protein Glucagon-like peptide 1 receptor Homo sapiens Potency n.a. 28183.8 nM DrugMatrix in vitro pharmacology data
NPT159 Individual protein Aberrant vpr protein Human immunodeficiency virus 1 Potency n.a. 14125.4 nM PMID[16933872]
NPT1043 Individual protein Glycoprotein hormones alpha chain Homo sapiens Potency n.a. 10000.0 nM PMID[8254347]
NPT105 Individual protein Muscleblind-like protein 1 Homo sapiens Potency n.a. 891.3 nM PMID[26595875]
NPT483 Individual protein Prelamin-A/C Homo sapiens Potency = 22387.2 nM DrugMatrix in vivo data: Biochemistry
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 7079.5 nM PMID[25913865]
NPT55 Individual protein Putative fructose-1,6-bisphosphate aldolase Giardia intestinalis Potency = 501.2 nM PMID[20022253]
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 11220.2 nM PMID[19654408]
NPT9 Individual protein DNA polymerase eta Homo sapiens Potency n.a. 89125.1 nM PMID[18417256]
NPT94 Individual protein Aldehyde dehydrogenase 1A1 Homo sapiens Potency = 39810.7 nM PMID[23837878]
NPT54 Individual protein Nonstructural protein 1 Influenza A virus Potency = 3981.1 nM PMID[20039643]
NPT444 Individual protein Ubiquitin carboxyl-terminal hydrolase 1 Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 7079.5 nM PMID[23910596]
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 17782.8 nM PMID[22916954]
NPT4674 Individual protein Apoptotic protease-activating factor 1 Homo sapiens IC50 > 100000.0 nM PMID[12502321]
NPT8 Individual protein DNA polymerase iota Homo sapiens Potency n.a. 100000.0 nM PMID[22695182]
NPT4674 Individual protein Apoptotic protease-activating factor 1 Homo sapiens IC50 = 14400.0 nM PMID[7130988]
NPT478 Individual protein Ataxin-2 Homo sapiens Potency n.a. 14125.4 nM PMID[21090801]
NPT861 Individual protein Isocitrate dehydrogenase [NADP] cytoplasmic Homo sapiens Potency n.a. 18356.4 nM DrugMatrix in vitro pharmacology data
NPT535 Individual protein Parathyroid hormone receptor Homo sapiens Potency n.a. 44668.4 nM PMID[14584959]
NPT536 Nucleic acid microRNA 21 Homo sapiens Potency = 23280.9 nM PMID[25338180]
NPT5055 Individual protein Mitochondrial import inner membrane translocase subunit TIM23 Saccharomyces cerevisiae S288c IC50 = 5320.0 nM DOI[10.1007/s00044-013-0498-3]
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 29092.9 nM PMID[23092389]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1083 Cell line A-375 Homo sapiens AC50 = 37758.0 nM PubChem BioAssay data set
NPT65 Cell line HepG2 Homo sapiens Potency n.a. 25118.9 nM PMID[22832312]
NPT71 Cell line HEK293 Homo sapiens Potency n.a. 11220.2 nM PMID[21868221]
NPT927 Cell line PBMC Homo sapiens EC50 = 16000.0 nM PMID[19804979]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 45000.0 nM PMID[18077425]
NPT81 Cell line A549 Homo sapiens IC50 = 4000.0 nM PMID[22731892]
NPT83 Cell line MCF7 Homo sapiens IC50 = 5000.0 nM PMID[25589938]
NPT170 Cell line SK-MEL-28 Homo sapiens IC50 = 5000.0 nM PMID[2824776]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 14715.7 nM PubChem BioAssay data set
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 4653.5 nM PMID[21705220]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae Potency = 11220.2 nM PMID[8411013]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. EC50 = 4000.0 nM PMID[22019229]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 3000.0 nM PMID[26706169]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 2000.0 nM PMID[26706169]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 5000.0 nM PMID[26706169]
NPT2 Others Unspecified n.a. Potency = 29092.9 nM PMID[20022253]
NPT2 Others Unspecified n.a. Potency n.a. 29092.9 nM PMID[20022253]
NPT2 Others Unspecified n.a. Potency n.a. 11220.2 nM PMID[16643028]
NPT2 Others Unspecified n.a. IC50 = 16600.0 nM PMID[19344127]
NPT841 Organism Leishmania major Leishmania major IC50 = 3300.0 nM PMID[24582402]
NPT2 Others Unspecified n.a. Ratio IC50 = 13.6 n.a. PMID[23434030]
NPT2 Others Unspecified n.a. Potency n.a. 2818.4 nM PMID[8699183]
NPT2 Others Unspecified n.a. Potency n.a. 22387.2 nM PMID[10579870]
NPT2 Others Unspecified n.a. Potency n.a. 20596.2 nM PMID[16040241]
NPT2 Others Unspecified n.a. AC50 = 15250.0 nM PMID[25647077]
NPT2 Others Unspecified n.a. Potency n.a. 39810.7 nM PMID[22583079]

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 NPC182646 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
0.6667 Remote Similarity NPC45537
0.641 Remote Similarity NPC180685
0.5854 Remote Similarity NPC486393
0.5714 Remote Similarity NPC205360
0.5556 Remote Similarity NPC43945
0.5455 Remote Similarity NPC481949
0.5385 Remote Similarity NPC486396
0.5333 Remote Similarity NPC84273

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC182646 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
0.5556 Remote Similarity NPD650 Phase 4

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