Natural Product: NPC57463

Natural Product IDNPC57463
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Primin
IUPAC Name 2-methoxy-6-pentylcyclohexa-2,5-diene-1,4-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL451919
PubChem CID 84800
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0001831] Carbonyl compounds
          • [CHEMONTID:0000118] Ketones
            • [CHEMONTID:0003487] Cyclic ketones
              • [CHEMONTID:0002495] Quinones
                • [CHEMONTID:0002384] Benzoquinones
                  • [CHEMONTID:0002494] P-benzoquinones

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 WLWIMKWZMGJRBS-UHFFFAOYSA-N
Standard InCHI InChI=1S/C12H16O3/c1-3-4-5-6-9-7-10(13)8-11(15-2)12(9)14/h7-8H,3-6H2,1-2H3
SMILES CCCCCC1=CC(=O)C=C(C1=O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   208.11 Volume:   223.377
?
Van der Waals volume.
Dense:   0.932 LogP:   2.998
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.784
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.431
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   8.0
TPSA:   43.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.513 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.52 Fsp3:   0.5
MCE-18:   7.0
?
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:   0.176 Fluc inhibitor:   0.643
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.193
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.328
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.996 Promiscuous compounds:   0.359

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.592 MDCK Permeability:   -4.556
Pgp-inhibitor:   0.625 Pgp-substrate:   0.025
PAMPA:   0.259
?
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):   0.813
20% Bioavailability (F20%):   0.257 30% Bioavailability (F30%):   0.552
50% Bioavailability (F50%):   0.585

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.089 MRP1:   0.791
Plasma Protein Binding (PPB):   98.805% Volume Distribution (VD):   0.564
Fu: 1.757%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.842
OATP1B3 inhibitor:   0.991 BCRP inhibitor:   0.094
BSEP inhibitor:   0.946

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.071 CYP2C19-substrate:   0.958
CYP2C9-inhibitor:   0.997 CYP2C9-substrate:   0.236
CYP2D6-inhibitor:   0.017 CYP2D6-substrate:   0.981
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.15 CYP2C8-inhibitor:   1.0
HLM stability:   0.904
?
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):  5.405 Half-life (T1/2):  1.148

ADMET: Toxicity

hERG Blockers:  0.141 hERG Blockers (10um):  0.582
Human Hepatotoxicity (H-HT):  0.705 Drug-induced Liver Injury (DILI):  0.451
AMES Toxicity:  0.548 Rat Oral Acute Toxicity:  0.41
Maximum Recommended Daily Dose:  0.576 Skin Sensitization:  0.924
Carcinogencity:  0.624 Eye Corrosion:  0.818
Eye Irritation:  0.991 Respiratory Toxicity:  0.611
Drug-induced Neurotoxicity:  0.368 Ototoxicity:  0.161
Hematotoxicity:  0.613 Drug-induced Nephrotoxicity:  0.315
Genotoxicity:  0.145 RPMI-8226 Immunitoxicity:  0.097
A549 Cytotoxicity:  0.17 Hek293 Cytotoxicity:  0.305
BCF:   1.651
?
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:   4.34
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.793
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.377
?
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
NPO31408 Miconia eriodonta Species Melastomataceae Eukaryota n.a. n.a. n.a. DOI[10.1021/np50069a029]
NPO25763 Miconia lepidota Species Melastomataceae Eukaryota n.a. Suriname rainforest n.a. PMID[11170656]
NPO25763 Miconia lepidota Species Melastomataceae Eukaryota n.a. n.a. n.a. PMID[11170656]
NPO31392 Miconia Genus Melastomataceae Eukaryota n.a. n.a. n.a. PMID[11170656]
NPO31192 Botryosphaeria mamane Species Botryosphaeriaceae Eukaryota n.a. n.a. n.a. PMID[17827773]
NPO3720 Primula obconica Species Primulaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO31192 Botryosphaeria mamane Species Botryosphaeriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23859 Primula elatior Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3953 Primula mistassinica Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18194 Primula modesta Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3953 Primula mistassinica Species Primulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23859 Primula elatior Species Primulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30733 Miconia sp Species Melastomataceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3720 Primula obconica Species Primulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18194 Primula modesta Species Primulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17252 Miconia sp. Species Melastomataceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3953 Primula mistassinica Species Primulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3720 Primula obconica Species Primulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18194 Primula modesta Species Primulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23859 Primula elatior Species Primulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3953 Primula mistassinica Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23859 Primula elatior Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25763 Miconia lepidota Species Melastomataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18194 Primula modesta Species Primulaceae 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
NPT324 Individual protein Cyclooxygenase-1 Ovis aries IC50 = 18920.0 nM PMID[32738413]
NPT31 Individual protein Cyclooxygenase-2 Homo sapiens IC50 = 1900.0 nM PMID[32738413]
NPT31 Individual protein Cyclooxygenase-2 Homo sapiens IC50 = 1900.0 nM PMID[34479036]
NPT570 Individual protein Arachidonate 5-lipoxygenase Homo sapiens IC50 = 1370.0 nM PMID[32738413]
NPT570 Individual protein Arachidonate 5-lipoxygenase Homo sapiens IC50 = 1370.0 nM PMID[34479036]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT179 Cell line A2780 Homo sapiens IC50 = 2.9 ug.mL-1 PMID[11170656]
NPT726 Cell line M109 Mus musculus IC50 = 10.0 ug.mL-1 PMID[11170656]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae Activity = 285.0 ug ml-1 PMID[11170656]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae Activity = 170.0 ug ml-1 PMID[11170656]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae Activity = 240.0 ug ml-1 PMID[11170656]
NPT312 Organism Saccharomyces cerevisiae Saccharomyces cerevisiae Activity = 48.0 ug ml-1 PMID[11170656]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus Activity = 48.8 mg PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus Activity = 48.4 mg PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus Activity = 42.2 mg PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus Activity = 26.8 mg PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus Activity = 4.9 mg PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus Activity = 0.1 mg PMID[18461966]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT489 Organism Coptotermes formosanus Coptotermes formosanus mortality = 8.3 % PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus mortality = 21.7 % PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus mortality = 25.0 % PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus mortality = 50.0 % PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus mortality = 1.7 % PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus mortality = 10.0 % PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus mortality = 40.0 % PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus mortality = 100.0 % PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus mortality = 0.0 % PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus mortality = 5.0 % PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus mortality = 36.7 % PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus mortality = 96.7 % PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus mortality = 3.3 % PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus mortality = 28.3 % PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus mortality = 80.0 % PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus mortality = 56.7 % PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus mortality = 91.7 % PMID[18461966]
NPT489 Organism Coptotermes formosanus Coptotermes formosanus mortality = 87.5 % PMID[18461966]





 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 NPC57463 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
0.9677 High Similarity NPC474400
0.9677 High Similarity NPC98897
0.9677 High Similarity NPC151728
0.9677 High Similarity NPC34622
0.9032 High Similarity NPC473494
0.8333 Intermediate Similarity NPC16119
0.7188 Intermediate Similarity NPC474805
0.6061 Remote Similarity NPC220191
0.525 Remote Similarity NPC606251
0.5238 Remote Similarity NPC473536
0.5122 Remote Similarity NPC263382

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC57463 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
0.8333 Intermediate Similarity NPD6108 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