Natural Product: NPC149246

Natural Product IDNPC149246
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Dodecanoylphloroglucinol
IUPAC Name 1-(2,4,6-trihydroxyphenyl)dodecan-1-one
Synonyms Dodecanoylphloroglucinol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2204424
PubChem CID 11771258
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0001831] Carbonyl compounds
          • [CHEMONTID:0000118] Ketones
            • [CHEMONTID:0003670] Aryl ketones
              • [CHEMONTID:0004296] Phenylketones
                • [CHEMONTID:0004298] Alkyl-phenylketones

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 CIJGEBXETKIQOK-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H28O4/c1-2-3-4-5-6-7-8-9-10-11-15(20)18-16(21)12-14(19)13-17(18)22/h12-13,19,21-22H,2-11H2,1H3
SMILES CCCCCCCCCCCC(=O)c1c(cc(cc1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   308.2 Volume:   335.943
?
Van der Waals volume.
Dense:   0.917 LogP:   6.054
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.949
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.843
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   11.0 Rigid Bonds:   7.0
TPSA:   77.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   1.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.401 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.202 Fsp3:   0.611
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:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.542 Fluc inhibitor:   0.436
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.075
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.068
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.78 Promiscuous compounds:   0.136

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.139 MDCK Permeability:   -4.748
Pgp-inhibitor:   0.007 Pgp-substrate:   0.065
PAMPA:   0.02
?
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):   0.028
20% Bioavailability (F20%):   0.164 30% Bioavailability (F30%):   0.874
50% Bioavailability (F50%):   0.949

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.061 MRP1:   0.971
Plasma Protein Binding (PPB):   98.615% Volume Distribution (VD):   1.021
Fu: 1.434%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.89
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.942
BSEP inhibitor:   0.164

ADMET: Metabolism

CYP1A2-inhibitor:   0.918 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.018 CYP2C19-substrate:   0.996
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.994
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.004 CYP2C8-inhibitor:   1.0
HLM stability:   0.619
?
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):  5.321 Half-life (T1/2):  0.798

ADMET: Toxicity

hERG Blockers:  0.202 hERG Blockers (10um):  0.802
Human Hepatotoxicity (H-HT):  0.358 Drug-induced Liver Injury (DILI):  0.074
AMES Toxicity:  0.158 Rat Oral Acute Toxicity:  0.317
Maximum Recommended Daily Dose:  0.555 Skin Sensitization:  0.933
Carcinogencity:  0.216 Eye Corrosion:  0.886
Eye Irritation:  0.999 Respiratory Toxicity:  0.976
Drug-induced Neurotoxicity:  0.06 Ototoxicity:  0.086
Hematotoxicity:  0.074 Drug-induced Nephrotoxicity:  0.072
Genotoxicity:  0.003 RPMI-8226 Immunitoxicity:  0.054
A549 Cytotoxicity:  0.792 Hek293 Cytotoxicity:  0.598
BCF:   1.444
?
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:   4.621
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.022
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.965
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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
NPO1768 Sansevieria ehrenbergii Species Asparagaceae Eukaryota n.a. African n.a. PMID[15921418]
NPO8160 Diospyros montana Species Ebenaceae Eukaryota n.a. n.a. n.a. PMID[17400463]
NPO11451 Lespedeza cyrtobotrya Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19102656]
NPO17154 Hymenaea oblongifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14332 Uvaria ferruginea Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1768 Sansevieria ehrenbergii Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9374 Veronica anagallis-aquatica Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8160 Diospyros montana Species Ebenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17618 Flaveria bidentis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11451 Lespedeza cyrtobotrya Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11451 Lespedeza cyrtobotrya Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11451 Lespedeza cyrtobotrya Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17618 Flaveria bidentis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14611 Teucrium fragile Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2535 Bunodactis xanthogrammica Species Actiniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11451 Lespedeza cyrtobotrya Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14332 Uvaria ferruginea Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22851 Kryptoperidinium foliaceum Species Peridiniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9374 Veronica anagallis-aquatica Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17009 Ptelea crenulata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17154 Hymenaea oblongifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO668 Cnidoscolus texanus Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1768 Sansevieria ehrenbergii Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12642 Podadenia thwaitesii n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO16062 Trichilia dregeana Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8160 Diospyros montana Species Ebenaceae 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
NPT115 Organism Mycobacterium tuberculosis H37Ra Mycobacterium tuberculosis H37Ra MIC = 50.0 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 NPC149246 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
0.7059 Intermediate Similarity NPC121259
0.6176 Remote Similarity NPC146642
0.6 Remote Similarity NPC600129
0.5806 Remote Similarity NPC209486
0.5676 Remote Similarity NPC95172
0.5429 Remote Similarity NPC276111
0.5294 Remote Similarity NPC294037
0.5263 Remote Similarity NPC320819
0.5122 Remote Similarity NPC242895
0.5122 Remote Similarity NPC607946

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC149246 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