Natural Product: NPC243272

Natural Product IDNPC243272
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-O-Methylembelin
IUPAC Name 2-hydroxy-5-methoxy-3-undecylcyclohexa-2,5-diene-1,4-dione
Synonyms 5-O-Methylembelin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL471270
PubChem CID 171489
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 KHBJLRRAMCJZLZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H28O4/c1-3-4-5-6-7-8-9-10-11-12-14-17(20)15(19)13-16(22-2)18(14)21/h13,20H,3-12H2,1-2H3
SMILES CCCCCCCCCCCC1=C(C(=O)C=C(C1=O)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   308.2 Volume:   335.943
?
Van der Waals volume.
Dense:   0.917 LogP:   4.85
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.828
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.9
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   11.0 Rigid Bonds:   8.0
TPSA:   63.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.454 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.499 Fsp3:   0.667
MCE-18:   8.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   0.447 Fluc inhibitor:   0.948
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.021
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.166
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.932 Promiscuous compounds:   0.178

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.008 MDCK Permeability:   -4.757
Pgp-inhibitor:   0.045 Pgp-substrate:   0.054
PAMPA:   0.055
?
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):   0.973
20% Bioavailability (F20%):   0.83 30% Bioavailability (F30%):   0.986
50% Bioavailability (F50%):   0.972

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.932
Plasma Protein Binding (PPB):   98.194% Volume Distribution (VD):   0.714
Fu: 1.574%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.913
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.601
BSEP inhibitor:   0.643

ADMET: Metabolism

CYP1A2-inhibitor:   0.299 CYP1A2-substrate:   0.981
CYP2C19-inhibitor:   0.064 CYP2C19-substrate:   0.525
CYP2C9-inhibitor:   0.996 CYP2C9-substrate:   0.854
CYP2D6-inhibitor:   0.955 CYP2D6-substrate:   0.057
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.831 CYP2C8-inhibitor:   0.948
HLM stability:   0.218
?
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):  3.141 Half-life (T1/2):  1.068

ADMET: Toxicity

hERG Blockers:  0.14 hERG Blockers (10um):  0.49
Human Hepatotoxicity (H-HT):  0.627 Drug-induced Liver Injury (DILI):  0.385
AMES Toxicity:  0.27 Rat Oral Acute Toxicity:  0.332
Maximum Recommended Daily Dose:  0.455 Skin Sensitization:  0.942
Carcinogencity:  0.499 Eye Corrosion:  0.895
Eye Irritation:  0.995 Respiratory Toxicity:  0.842
Drug-induced Neurotoxicity:  0.129 Ototoxicity:  0.173
Hematotoxicity:  0.472 Drug-induced Nephrotoxicity:  0.262
Genotoxicity:  0.001 RPMI-8226 Immunitoxicity:  0.076
A549 Cytotoxicity:  0.314 Hek293 Cytotoxicity:  0.18
BCF:   1.245
?
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:   4.778
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.192
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.848
?
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
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. twig n.a. DOI[10.1021/np50063a031]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. stem n.a. DOI[10.1021/np50063a031]
NPO20142 Embelia schimperi Species Primulaceae Eukaryota n.a. n.a. n.a. PMID[11054840]
NPO31207 Oxalis erythrorhiza Species Oxalidaceae Eukaryota n.a. n.a. n.a. PMID[12963150]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. n.a. n.a. PMID[15165134]
NPO26772 Lysimachia punctata Species Primulaceae Eukaryota n.a. root n.a. PMID[15890461]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. twig n.a. PMID[16254827]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. stem n.a. PMID[16254827]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. fruit n.a. PMID[17124632]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. leaf n.a. PMID[17124632]
NPO15741 Embelia ribes Species Primulaceae Eukaryota roots n.a. n.a. PMID[17125236]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. n.a. n.a. PMID[17125236]
NPO15388 Eucalyptus globulus Species Myrtaceae Eukaryota n.a. fruit n.a. PMID[18020353]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. n.a. n.a. PMID[22316191]
NPO15388 Eucalyptus globulus Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[22934600]
NPO15388 Eucalyptus globulus Species Myrtaceae Eukaryota n.a. whole plant n.a. PMID[23678820]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. n.a. n.a. PMID[2778454]
NPO23736 Myrsine africana Species Primulaceae Eukaryota root n.a. n.a. PMID[2778455]
NPO23736 Myrsine africana Species Primulaceae Eukaryota n.a. n.a. n.a. PMID[29300477]
NPO15388 Eucalyptus globulus Species Myrtaceae Eukaryota Fruits n.a. n.a. PMID[30543429]
NPO15388 Eucalyptus globulus Species Myrtaceae Eukaryota Fruits n.a. n.a. PMID[30848923]
NPO15388 Eucalyptus globulus Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[35108453]
NPO15388 Eucalyptus globulus Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[36903935]
NPO15388 Eucalyptus globulus Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[37047195]
NPO15388 Eucalyptus globulus Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[37179510]
NPO15388 Eucalyptus globulus Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[38263385]
NPO15388 Eucalyptus globulus Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[38380569]
NPO15388 Eucalyptus globulus Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[39592457]
NPO15388 Eucalyptus globulus Species Myrtaceae Eukaryota Leaves n.a. n.a. PMID[8864235]
NPO23736 Myrsine africana Species Primulaceae Eukaryota n.a. fruit n.a. Database[Article]
NPO20142 Embelia schimperi Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15388 Eucalyptus globulus Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23736 Myrsine africana Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15388 Eucalyptus globulus Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23736 Myrsine africana Species Primulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20142 Embelia schimperi Species Primulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23736 Myrsine africana Species Primulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15388 Eucalyptus globulus Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15388 Eucalyptus globulus Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26772 Lysimachia punctata Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15388 Eucalyptus globulus Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23736 Myrsine africana Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15741 Embelia ribes Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17145 Aegiceras corniculatum Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20142 Embelia schimperi 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
NPT1119 Individual protein Arachidonate 12-lipoxygenase Homo sapiens Activity = 138.4 % PMID[25765759]
NPT3167 Individual protein Macrophage-expressed gene 1 protein Homo sapiens IC50 = 9100.0 nM PMID[25765759]
NPT792 Individual protein Arachidonate 15-lipoxygenase Homo sapiens Activity = 131.2 % PMID[25765759]
NPT570 Individual protein Arachidonate 5-lipoxygenase Homo sapiens IC50 = 680.0 nM PMID[25765759]
NPT570 Individual protein Arachidonate 5-lipoxygenase Homo sapiens IC50 = 3800.0 nM PMID[25765759]
NPT570 Individual protein Arachidonate 5-lipoxygenase Homo sapiens IC50 = 1300.0 nM PMID[25765759]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT116 Cell line HL-60 Homo sapiens IC50 = 3.0 ug.mL-1 PMID[15165134]
NPT181 Cell line Bel-7402 Homo sapiens IC50 = 3.6 ug.mL-1 PMID[15165134]
NPT165 Cell line HeLa Homo sapiens IC50 = 9.0 ug.mL-1 PMID[15165134]
NPT466 Cell line U-937 Homo sapiens IC50 = 1.5 ug.mL-1 PMID[15165134]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC = 32.9 ug.mL-1 DOI[10.1007/s00044-013-0485-8]
NPT2527 Organism Pythium ultimum Pythium ultimum IZ = 8.0 mm PMID[2778454]
NPT790 Organism Mycobacterium tuberculosis H37Rv Mycobacterium tuberculosis H37Rv MIC = 15.0 ug.mL-1 DOI[10.1007/s00044-013-0485-8]
NPT2 Others Unspecified n.a. IC50 = 90190.0 nM PMID[24731276]

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 NPC243272 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
1.0 High Similarity NPC146376
1.0 High Similarity NPC125578
0.8718 High Similarity NPC94743
0.7949 Intermediate Similarity NPC264178
0.7674 Intermediate Similarity NPC291062
0.6923 Remote Similarity NPC53109
0.6889 Remote Similarity NPC262673
0.5745 Remote Similarity NPC487227
0.5476 Remote Similarity NPC606251
0.537 Remote Similarity NPC603676
0.5238 Remote Similarity NPC7029
0.5238 Remote Similarity NPC143168
0.5116 Remote Similarity NPC474400
0.5116 Remote Similarity NPC98897
0.5116 Remote Similarity NPC151728
0.5116 Remote Similarity NPC34622
0.5111 Remote Similarity NPC134385

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC243272 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
0.5238 Remote Similarity NPD2664 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