Natural Product: NPC57552

Natural Product IDNPC57552
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1-Methoxy-2-Methyl-Anthraquinone
IUPAC Name 1-methoxy-2-methylanthracene-9,10-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL41178
PubChem CID 3534338
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000018] Anthracenes
        • [CHEMONTID:0000151] Anthraquinones

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 MZFYROVNJMBHPG-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O3/c1-9-7-8-12-13(16(9)19-2)15(18)11-6-4-3-5-10(11)14(12)17/h3-8H,1-2H3
SMILES Cc1ccc2c(C(=O)c3ccccc3C2=O)c1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   252.08 Volume:   264.902
?
Van der Waals volume.
Dense:   0.952 LogP:   3.742
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.492
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.751
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   43.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.669 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.92 Fsp3:   0.125
MCE-18:   34.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   0.13 Fluc inhibitor:   0.651
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.336
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.792
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.663 Promiscuous compounds:   0.21

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.63 MDCK Permeability:   -4.597
Pgp-inhibitor:   1.0 Pgp-substrate:   0.124
PAMPA:   0.218
?
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):   0.085
20% Bioavailability (F20%):   0.021 30% Bioavailability (F30%):   0.697
50% Bioavailability (F50%):   0.959

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.083 MRP1:   0.597
Plasma Protein Binding (PPB):   97.966% Volume Distribution (VD):   0.294
Fu: 1.681%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.988
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.186
BSEP inhibitor:   0.975

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.014
CYP2C19-inhibitor:   0.337 CYP2C19-substrate:   0.168
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.098
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.29
CYP3A4-inhibitor:   0.064 CYP3A4-substrate:   0.047
CYP2B6-substrate:   0.015 CYP2C8-inhibitor:   0.963
HLM stability:   0.442
?
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):  5.826 Half-life (T1/2):  1.24

ADMET: Toxicity

hERG Blockers:  0.173 hERG Blockers (10um):  0.645
Human Hepatotoxicity (H-HT):  0.698 Drug-induced Liver Injury (DILI):  0.871
AMES Toxicity:  0.844 Rat Oral Acute Toxicity:  0.414
Maximum Recommended Daily Dose:  0.3 Skin Sensitization:  0.729
Carcinogencity:  0.889 Eye Corrosion:  0.048
Eye Irritation:  0.984 Respiratory Toxicity:  0.662
Drug-induced Neurotoxicity:  0.68 Ototoxicity:  0.303
Hematotoxicity:  0.775 Drug-induced Nephrotoxicity:  0.396
Genotoxicity:  0.292 RPMI-8226 Immunitoxicity:  0.101
A549 Cytotoxicity:  0.382 Hek293 Cytotoxicity:  0.34
BCF:   1.763
?
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:   4.197
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.814
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.673
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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
NPO19792 Populus tomentosa Species Salicaceae Eukaryota n.a. n.a. n.a. PMID[22860454]
NPO18951 Ligusticum sinense Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[26521454]
NPO20880 Conocybe siliginea Species Bolbitiaceae Eukaryota n.a. n.a. n.a. PMID[32816486]
NPO20880 Conocybe siliginea Species Bolbitiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20572 Vepris louisii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4192 Gynochthodes umbellata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18951 Ligusticum sinense Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30535 Morinda umbellata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8020 Lychnophora columnaris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19792 Populus tomentosa Species Salicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21199 Alangium platanifolium Species Cornaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18951 Ligusticum sinense Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19792 Populus tomentosa Species Salicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21199 Alangium platanifolium Species Cornaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30535 Morinda umbellata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20572 Vepris louisii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21199 Alangium platanifolium Species Cornaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19792 Populus tomentosa Species Salicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18951 Ligusticum sinense Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4192 Gynochthodes umbellata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18951 Ligusticum sinense Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19792 Populus tomentosa Species Salicaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO30535 Morinda umbellata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18951 Ligusticum sinense Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO18951 Ligusticum sinense Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15980 Croton penduliflorus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21199 Alangium platanifolium Species Cornaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4192 Gynochthodes umbellata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20364 Ophelia bicornis Species Opheliidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8020 Lychnophora columnaris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20572 Vepris louisii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19956 Pulveroboletus retipes Species Boletaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19792 Populus tomentosa Species Salicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20064 Litsea konishii Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20880 Conocybe siliginea Species Bolbitiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20822 Asperula odora Species Rubiaceae 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
NPT279 Individual protein Leukocyte elastase Homo sapiens IC50 > 60000.0 nM PMID[1578486]

In vitro activity

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

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 NPC57552 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
0.6 Remote Similarity NPC67172
0.5946 Remote Similarity NPC223336
0.5476 Remote Similarity NPC208806
0.5385 Remote Similarity NPC603805
0.5366 Remote Similarity NPC160777
0.5349 Remote Similarity NPC49282
0.5227 Remote Similarity NPC290954
0.5135 Remote Similarity NPC177925

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC57552 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
NPD

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